Adiponectin: Difference between revisions

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{{GNF_Protein_box
{{Infobox_gene}}
| image = PBB_Protein_ADIPOQ_image.jpg
'''Adiponectin''' (also referred to as '''GBP-28''', '''apM1''', '''AdipoQ''' and '''Acrp30''') is a [[protein hormone]] which is involved in regulating [[glucose]] levels as well as [[fatty acid]] breakdown. In humans it is encoded by the ''ADIPOQ'' [[gene]] and it is produced in adipose tissue.<ref name="pmid8619847">{{cite journal | vauthors = Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matsubara K | title = cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1) | journal = Biochemical and Biophysical Research Communications | volume = 221 | issue = 2 | pages = 286–9 | date = April 1996 | pmid = 8619847 | doi = 10.1006/bbrc.1996.0587 }}</ref>
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1c28.
| Name = Adiponectin, C1Q and collagen domain containing
| HGNCid = 13633
| Symbol = ADIPOQ
| AltSymbols =; ACDC; ACRP30; APM-1; APM1; GBP28; adiponectin
| OMIM = 605441
| ECnumber = 
| Homologene = 3525
| MGIid = 106675
| GeneAtlas_image1 = PBB_GE_ADIPOQ_207175_at_tn.png
<!-- The Following entry is a time stamp of the last bot update.  It is typically hidden data -->
| DateOfBotUpdate = 18:47, 21 October 2007 (UTC)
| Function = {{GNF_GO|id=GO:0005179 |text = hormone activity}}
| Component = {{GNF_GO|id=GO:0005576 |text = extracellular region}} {{GNF_GO|id=GO:0005615 |text = extracellular space}} {{GNF_GO|id=GO:0005737 |text = cytoplasm}} {{GNF_GO|id=GO:0005783 |text = endoplasmic reticulum}}
| Process = {{GNF_GO|id=GO:0006006 |text = glucose metabolic process}} {{GNF_GO|id=GO:0006091 |text = generation of precursor metabolites and energy}} {{GNF_GO|id=GO:0006635 |text = fatty acid beta-oxidation}} {{GNF_GO|id=GO:0006817 |text = phosphate transport}} {{GNF_GO|id=GO:0009749 |text = response to glucose stimulus}} {{GNF_GO|id=GO:0042593 |text = glucose homeostasis}} {{GNF_GO|id=GO:0043123 |text = positive regulation of I-kappaB kinase/NF-kappaB cascade}} {{GNF_GO|id=GO:0045721 |text = negative regulation of gluconeogenesis}} {{GNF_GO|id=GO:0045923 |text = positive regulation of fatty acid metabolic process}} {{GNF_GO|id=GO:0046326 |text = positive regulation of glucose import}} {{GNF_GO|id=GO:0051260 |text = protein homooligomerization}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 9370
    | Hs_Ensembl = ENSG00000181092
    | Hs_RefseqProtein = NP_004788
    | Hs_RefseqmRNA = NM_004797
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 3
    | Hs_GenLoc_start = 188043157
    | Hs_GenLoc_end = 188058944
    | Hs_Uniprot = Q15848
    | Mm_EntrezGene = 11450
    | Mm_Ensembl = ENSMUSG00000022878
    | Mm_RefseqmRNA = NM_009605
    | Mm_RefseqProtein = NP_033735
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 16
    | Mm_GenLoc_start = 23061870
    | Mm_GenLoc_end = 23073302
    | Mm_Uniprot = Q6GTX4
  }}
}}


{{protein
== Structure  ==
| Name = adiponectin receptor 1
Adiponectin is a 244-amino-acid-long polypeptide [[Hormone#Animal|(protein)]]. There are four distinct regions of adiponectin. The first is a short signal sequence that targets the hormone for secretion outside the cell; next is a short region that varies between species; the third is a 65-amino acid region with similarity to collagenous proteins; the last is a globular domain. Overall this protein shows similarity to the complement 1Q factors ([[C1q|C1Q]]). However, when the 3-dimensional structure of the globular region was determined, a striking similarity to [[Tumor necrosis factor-alpha|TNFα]] was observed, despite unrelated protein sequences.<ref name="pmid9512423">{{cite journal | vauthors = Shapiro L, Scherer PE | title = The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor | journal = Current Biology | volume = 8 | issue = 6 | pages = 335–8 | date = March 1998 | pmid = 9512423 | doi = 10.1016/S0960-9822(98)70133-2 }}</ref>
| caption =  
| image =  
| width =  
| HGNCid = 24040
| Symbol = ADIPOR1
| AltSymbols =
| EntrezGene = 51094
| OMIM = 607945
| RefSeq = NM_015999
| UniProt = Q96A54
| PDB =
| ECnumber =
| Chromosome = 1
| Arm = q
| Band = 32.1
| LocusSupplementaryData =  
}}
{{protein
| Name = adiponectin receptor 2
| caption =  
| image =  
| width =  
| HGNCid = 24041
| Symbol = ADIPOR2
| AltSymbols =  
| EntrezGene = 79602
| OMIM = 607946
| RefSeq = NM_024551
| UniProt = Q86V24
| PDB =
| ECnumber =
| Chromosome = 12
| Arm = p
| Band = 13
| LocusSupplementaryData =
}}
{{SI}}
__NOTOC__
{{GS}}


== Function ==
Adiponectin is a protein [[hormone]] that modulates a number of metabolic processes, including [[glucose]] regulation and [[fatty acid]] [[oxidation]].<ref name="pmid12611609">{{cite journal | vauthors = Díez JJ, Iglesias P | title = The role of the novel adipocyte-derived hormone adiponectin in human disease | journal = European Journal of Endocrinology | volume = 148 | issue = 3 | pages = 293–300 | date = March 2003 | pmid = 12611609 | doi = 10.1530/eje.0.1480293 }}</ref> Adiponectin is secreted from [[adipose tissue]] (and also from the [[placenta]] in pregnancy<ref name="pmid16570162">{{cite journal | vauthors = Chen J, Tan B, Karteris E, Zervou S, Digby J, Hillhouse EW, Vatish M, Randeva HS | title = Secretion of adiponectin by human placenta: differential modulation of adiponectin and its receptors by cytokines | journal = Diabetologia | volume = 49 | issue = 6 | pages = 1292–302 | date = June 2006 | pmid = 16570162 | doi = 10.1007/s00125-006-0194-7 }}</ref>) into the [[blood]]stream and is very abundant in [[blood plasma|plasma]] relative to many hormones. Many studies have found adiponectin to be inversely correlated with body mass index in patient populations.<ref name="pmid12436346">{{cite journal | vauthors = Ukkola O, Santaniemi M | title = Adiponectin: a link between excess adiposity and associated comorbidities? | journal = Journal of Molecular Medicine | volume = 80 | issue = 11 | pages = 696–702 | date = November 2002 | pmid = 12436346 | doi = 10.1007/s00109-002-0378-7 }}</ref> However, a meta analysis was not able to confirm this association in healthy adults.<ref name="pmid21364526">{{cite journal | vauthors = Kuo SM, Halpern MM | title = Lack of association between body mass index and plasma adiponectin levels in healthy adults | journal = International Journal of Obesity | volume = 35 | issue = 12 | pages = 1487–94 | date = December 2011 | pmid = 21364526 | doi = 10.1038/ijo.2011.20 }}</ref> Circulating adiponectin concentrations increase during caloric restriction in animals and humans, such as in patients with [[anorexia nervosa]]. This observation is surprising, given that adiponectin is produced by adipose tissue. However, a recent study suggests that adipose tissue within bone marrow, which increases during caloric restriction, contributes to elevated circulating adiponectin in this context.<ref name="pmid24998914">{{cite journal | vauthors = Cawthorn WP, Scheller EL, Learman BS, Parlee SD, Simon BR, Mori H, Ning X, Bree AJ, Schell B, Broome DT, Soliman SS, DelProposto JL, Lumeng CN, Mitra A, Pandit SV, Gallagher KA, Miller JD, Krishnan V, Hui SK, Bredella MA, Fazeli PK, Klibanski A, Horowitz MC, Rosen CJ, MacDougald OA | title = Bone marrow adipose tissue is an endocrine organ that contributes to increased circulating adiponectin during caloric restriction | journal = Cell Metabolism | volume = 20 | issue = 2 | pages = 368–75 | date = August 2014 | pmid = 24998914 | pmc = 4126847 | doi = 10.1016/j.cmet.2014.06.003 }}</ref>


Transgenic mice with increased adiponectin show reduced [[Adipose tissue|adipocyte]] [[Cellular differentiation|differentiation]] and increased energy expenditure associated with mitochondrial [[Uncoupling protein|uncoupling]].<ref name="pmid17204560">{{cite journal | vauthors = Bauche IB, El Mkadem SA, Pottier AM, Senou M, Many MC, Rezsohazy R, Penicaud L, Maeda N, Funahashi T, Brichard SM | title = Overexpression of adiponectin targeted to adipose tissue in transgenic mice: impaired adipocyte differentiation | journal = Endocrinology | volume = 148 | issue = 4 | pages = 1539–49 | date = April 2007 | pmid = 17204560 | doi = 10.1210/en.2006-0838 }}</ref> The hormone plays a role in the suppression of the metabolic derangements that may result in [[Diabetes mellitus type 2|type 2 diabetes]],<ref name="pmid12436346"/> [[obesity]], [[atherosclerosis]],<ref name="pmid12611609"/> [[non-alcoholic fatty liver disease]] (NAFLD) and an [[Independent variable|independent]] [[risk factor]] for [[metabolic syndrome]].<ref name="pmid19258676">{{cite journal | vauthors = Renaldi O, Pramono B, Sinorita H, Purnomo LB, Asdie RH, Asdie AH | title = Hypoadiponectinemia: a risk factor for metabolic syndrome | journal = Acta Medica Indonesiana | volume = 41 | issue = 1 | pages = 20–4 | date = January 2009 | pmid = 19258676 }}</ref> Adiponectin in combination with [[leptin]] has been shown to completely reverse [[insulin resistance]] in mice.<ref name="pmid11479627">{{cite journal | vauthors = Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T | title = The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity | journal = Nature Medicine | volume = 7 | issue = 8 | pages = 941–6 | date = August 2001 | pmid = 11479627 | doi = 10.1038/90984 }}</ref>


Adiponectin is secreted into the bloodstream where it accounts for approximately 0.01% of all plasma protein at around 5-10 μg/mL (mg/L). In adults, plasma concentrations are higher in females than males, and are reduced in diabetics compared to non-diabetics. Weight reduction significantly increases circulating concentrations.<ref name="pmid18378021">{{cite journal | vauthors = Coppola A, Marfella R, Coppola L, Tagliamonte E, Fontana D, Liguori E, Cirillo T, Cafiero M, Natale S, Astarita C | title = Effect of weight loss on coronary circulation and adiponectin levels in obese women | journal = International Journal of Cardiology | volume = 134 | issue = 3 | pages = 414–6 | date = May 2009 | pmid = 18378021 | doi = 10.1016/j.ijcard.2007.12.087 }}</ref>


'''Adiponectin''' (also referred to as '''Acrp30''', '''apM1''') is a protein [[hormone]] that modulates a number of metabolic processes, including [[glucose]] regulation and [[fatty acid]] [[catabolism]]. Adiponectin is exclusively secreted from [[adipose tissue]] into the [[blood]]stream and is very abundant in [[blood plasma|plasma]] relative to many hormones. Levels of the hormone are inversely correlated with body fat percentage. The hormone plays a role in the suppression of the metabolic derangements that may result in [[Diabetes mellitus type 2|type 2 diabetes]], [[obesity]], [[atherosclerosis]] and [[non-alcoholic fatty liver disease]] (NAFLD).
Adiponectin automatically self-associates into larger structures. Initially, three adiponectin molecules bind together to form a homotrimer. The [[Protein trimer|trimer]]s continue to self-associate and form hexamers or dodecamers. Like the plasma concentration, the relative levels of the higher-order structures are sexually dimorphic, where females have increased proportions of the high-molecular weight forms. Recent studies showed that the high-molecular weight form may be the most biologically active form regarding glucose homeostasis.<ref name="Oh_2007">{{cite journal | vauthors = Oh DK, Ciaraldi T, Henry RR | title = Adiponectin in health and disease | journal = Diabetes, Obesity & Metabolism | volume = 9 | issue = 3 | pages = 282–9 | date = May 2007 | pmid = 17391153 | doi = 10.1111/j.1463-1326.2006.00610.x }}</ref> High-molecular-weight adiponectin was further found to be associated with a lower risk of diabetes with similar magnitude of association as total adiponectin.<ref name="pmid20719834">{{cite journal | vauthors = Zhu N, Pankow JS, Ballantyne CM, Couper D, Hoogeveen RC, Pereira M, Duncan BB, Schmidt MI | title = High-molecular-weight adiponectin and the risk of type 2 diabetes in the ARIC study | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 95 | issue = 11 | pages = 5097–104 | date = November 2010 | pmid = 20719834 | pmc = 2968724 | doi = 10.1210/jc.2010-0716 }}</ref> However, [[coronary artery disease]] has been found to be positively associated with high molecular weight adiponectin, but not with low molecular weight adiponectin.<ref>{{cite journal | vauthors = Rizza S, Gigli F, Galli A, Micchelini B, Lauro D, Lauro R, Federici M | title = Adiponectin isoforms in elderly patients with or without coronary artery disease | journal = Journal of the American Geriatrics Society | volume = 58 | issue = 4 | pages = 702–6 | date = April 2010 | pmid = 20398150 | doi = 10.1111/j.1532-5415.2010.02773.x }}</ref>


==Research history==
Adiponectin exerts some of its weight reduction effects via the [[brain]]. This is similar to the action of '''[[leptin]]''',<ref name="pmid15544426">{{cite journal | vauthors = Nedvídková J, Smitka K, Kopský V, Hainer V | title = Adiponectin, an adipocyte-derived protein | journal = Physiological Research | volume = 54 | issue = 2 | pages = 133–40 | year = 2005 | pmid = 15544426 | doi =  | url = http://www.biomed.cas.cz/physiolres/pdf/54/54_133.pdf }}</ref> but the two hormones perform complementary actions, and can have synergistic effects.{{clarify|date=May 2015}}
Adiponectin was first characterised in mice as a [[mRNA|transcript]] overexpressed in preadipocytes (precursors of fat cells) differentiating into [[adipocytes]]. The human homologue was identified as the most abundant transcript in adipose tissue. Contrary to expectations, despite being produced in [[adipose tissue]], adiponectin was found to be decreased in [[obesity]]. This downregulation has not been fully explained. The gene was localised to chromosome 3p27, a region highlighted as affecting genetic susceptibility to type 2 diabetes and obesity. Supplementation by differing forms of adiponectin were able to improve [[insulin]] control, blood glucose and triglyceride levels in mouse models.


The gene was investigated for variants that predispose to type 2 diabetes. Several [[single nucleotide polymorphism]]s in the coding region and surrounding sequence were identified from several different populations, with varying prevalences, degrees of association and strength of effect on type 2 diabetes.
== Receptors ==
{{Main article|Adiponectin receptor}}
Adiponectin binds to a number of receptors. So far, two [[receptor (biochemistry)|receptors]] have been identified with [[Homology (biology)|homology]] to [[G protein-coupled receptor]]s, and one receptor similar to the cadherin family:<ref name="pmid12802337">{{cite journal | vauthors = Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekawa S, Waki H, Tsuno NH, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu T, Nagai R, Kadowaki T | title = Cloning of adiponectin receptors that mediate antidiabetic metabolic effects | journal = Nature | volume = 423 | issue = 6941 | pages = 762–9 | date = June 2003 | pmid = 12802337 | doi = 10.1038/nature01705 }}</ref><ref name="pmid15210937">{{cite journal | vauthors = Hug C, Wang J, Ahmad NS, Bogan JS, Tsao TS, Lodish HF | title = T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 101 | issue = 28 | pages = 10308–13 | date = July 2004 | pmid = 15210937 | pmc = 478568 | doi = 10.1073/pnas.0403382101 }}</ref>
* [[Adiponectin receptor 1]] (AdipoR1)
* [[Adiponectin receptor 2]] (AdipoR2)
* [[T-cadherin|T-cadherin - CDH13]]


==Structure and function==
These have distinct tissue specificities within the body and have different affinities to the various forms of adiponectin. The receptors affect the downstream target [[AMP-activated protein kinase|AMP kinase]], an important cellular metabolic rate control point. Expression of the receptors is correlated with insulin levels, as well as reduced in mouse models of diabetes, particularly in [[skeletal muscle]] and adipose tissue.<ref name="pmid17052201">{{cite journal | vauthors = Fang X, Sweeney G | title = Mechanisms regulating energy metabolism by adiponectin in obesity and diabetes | journal = Biochemical Society Transactions | volume = 34 | issue = Pt 5 | pages = 798–801 | date = November 2006 | pmid = 17052201 | doi = 10.1042/BST0340798 }}</ref><ref name="pmid18222103">{{cite journal | vauthors = Bonnard C, Durand A, Vidal H, Rieusset J | title = Changes in adiponectin, its receptors and AMPK activity in tissues of diet-induced diabetic mice | journal = Diabetes & Metabolism | volume = 34 | issue = 1 | pages = 52–61 | date = February 2008 | pmid = 18222103 | doi = 10.1016/j.diabet.2007.09.006 }}</ref>. In 2016, the University of Tokyo announced it was launching an investigation into anonymously made claims of fabricated and falsified data on the identification of AdipoR1 and AdipoR2<ref name="Dennis">[http://www.sciencemag.org/news/2016/09/university-tokyo-investigate-data-manipulation-charges-against-six-prominent-research University of Tokyo to investigate data manipulation charges against six prominent research groups] ScienceInsider, Dennis Normile, Sep 20, 2016</ref>.
Adiponectin is a 244-amino-acid-long polypeptide. There are four distinct regions of adiponectin. The first is a short signal squence that targets the hormone for secretion outside the cell; next is a short region that varies between species; the third is a 65-amino acid region with similarity to collagenous proteins; the last is a globular domain. Overall this gene shows similarity to the complement 1Q factors. However, when the 3-dimensional structure of the globular region was determined, a striking similarity to [[Tumor necrosis factor-alpha|TNFα]] was observed, despite unrelated protein sequences.


Adiponectin is secreted into the bloodsteam where it accounts for approximately 0.01% of all plasma protein at around 5-10 μg/mL. Plasma concentrations reveal a [[sexual dimorphism]], with females having higher levels than males. Levels of adiponectin are reduced in diabetics compared to non-diabetics. Weight reduction significantly increases circulating levels.
== Discovery ==


Adiponectin automatically self-associates into larger structures. Initially, three adiponectin molecules bind together to form a homotrimer. The [[trimer]]s continue to self-associate and form hexamers or dodecamers. Like the plasma concentration, the relative levels of the higher-order structures are sexually dimorphic, where females have increased proportions of the high-molecular weight forms. Questions remain about what the physiologically active forms of the protein are and how they carry out their action.  
Adiponectin was first characterised in 1995 in differentiating 3T3-L1 adipocytes (Scherer PE et al.).<ref>{{cite journal | vauthors = Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF | title = A novel serum protein similar to C1q, produced exclusively in adipocytes | journal = The Journal of Biological Chemistry | volume = 270 | issue = 45 | pages = 26746–9 | date = November 1995 | pmid = 7592907 | doi = 10.1074/jbc.270.45.26746 }}</ref> In 1996 it was characterised in mice as the mRNA transcript most highly expressed in adipocytes<ref name="pmid8619847"/>. In 2007, adiponectin was identified as a [[mRNA|transcript]] highly expressed in preadipocytes<ref name="pmid17495599">{{cite journal | vauthors = Lara-Castro C, Fu Y, Chung BH, Garvey WT | title = Adiponectin and the metabolic syndrome: mechanisms mediating risk for metabolic and cardiovascular disease | journal = Current Opinion in Lipidology | volume = 18 | issue = 3 | pages = 263–70 | date = June 2007 | pmid = 17495599 | doi = 10.1097/MOL.0b013e32814a645f }}</ref> (precursors of fat cells) differentiating into [[adipocytes]].<ref name="pmid17495599"/><ref name="pmid14551151">{{cite journal | vauthors = Matsuzawa Y, Funahashi T, Kihara S, Shimomura I | title = Adiponectin and metabolic syndrome | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | volume = 24 | issue = 1 | pages = 29–33 | date = January 2004 | pmid = 14551151 | doi = 10.1161/01.ATV.0000099786.99623.EF }}</ref>


Adiponectin binds to a number of receptors. So far, two [[receptor (biochemistry)|receptors]] have been identified, with [[Homology (biology)|homology]] to [[G protein-coupled receptor]]s. These have distinct tissue specificities within the body and have different affinities to the various forms of adiponectin. The receptors affect the downstream target [[AMP-activated protein kinase|AMP kinase]], an important cellular metabolic rate control point. Expression of the receptors are correlated with insulin levels, as well as reduced in mouse models of diabetes, particularly in [[skeletal muscle]] and adipose tissue.  
The human homologue was identified as the most abundant transcript in adipose tissue. Contrary to expectations, despite being produced in [[adipose tissue]], adiponectin was found to be decreased in [[obesity]].<ref name="pmid12611609"/><ref name="pmid12436346"/><ref name="pmid15544426"/> This downregulation has not been fully explained. The gene was localised to chromosome 3q27, a region highlighted as affecting genetic susceptibility to type 2 diabetes and obesity. Supplementation by differing forms of adiponectin was able to improve [[insulin]] control, blood glucose and triglyceride levels in mouse models.


Adiponectin exerts some of its weight reduction effects via the [[brain]]. This is similar to the action of '''[[leptin]]''', but the two hormones perform complementary actions, and can have additive effects.
The gene was investigated for variants that predispose to type 2 diabetes.<ref name="pmid15544426"/><ref name="pmid17495599"/><ref name="pmid15794918">{{cite journal | vauthors = Hara K, Yamauchi T, Kadowaki T | title = Adiponectin: an adipokine linking adipocytes and type 2 diabetes in humans | journal = Current Diabetes Reports | volume = 5 | issue = 2 | pages = 136–40 | date = April 2005 | pmid = 15794918 | doi = 10.1007/s11892-005-0041-0 }}</ref><ref name="pmid12728641">{{cite journal | vauthors = Vasseur F, Leprêtre F, Lacquemant C, Froguel P | title = The genetics of adiponectin | journal = Current Diabetes Reports | volume = 3 | issue = 2 | pages = 151–8 | date = April 2003 | pmid = 12728641 | doi = 10.1007/s11892-003-0039-4 }}</ref><ref name="pmid15780820">{{cite journal | vauthors = Hug C, Lodish HF | title = The role of the adipocyte hormone adiponectin in cardiovascular disease | journal = Current Opinion in Pharmacology | volume = 5 | issue = 2 | pages = 129–34 | date = April 2005 | pmid = 15780820 | doi = 10.1016/j.coph.2005.01.001 }}</ref><ref name="pmid17112391">{{cite journal | vauthors = Vasseur F, Meyre D, Froguel P | title = Adiponectin, type 2 diabetes and the metabolic syndrome: lessons from human genetic studies | journal = Expert Reviews in Molecular Medicine | volume = 8 | issue = 27 | pages = 1–12 | date = November 2006 | pmid = 17112391 | doi = 10.1017/S1462399406000147 }}</ref> Several [[single nucleotide polymorphism]]s in the coding region and surrounding sequence were identified from several different populations, with varying prevalences, degrees of association and strength of effect on type 2 diabetes. [[Berberine]], an isoquinoline alkaloid, has been shown to increase adiponectin expression<ref name="pmid20016706">{{cite journal | vauthors = Choi BH, Kim YH, Ahn IS, Ha JH, Byun JM, Do MS | title = The inhibition of inflammatory molecule expression on 3T3-L1 adipocytes by berberine is not mediated by leptin signaling | journal = Nutrition Research and Practice | volume = 3 | issue = 2 | pages = 84–8 | year = 2009 | pmid = 20016706 | pmc = 2788178 | doi = 10.4162/nrp.2009.3.2.84 }}</ref> which partly explains its beneficial effects on metabolic disturbances. Mice fed the [[omega-3 fatty acid]]s [[eicosapentaenoic acid]]&nbsp;(EPA) and [[docosahexaenoic acid]]&nbsp;(DHA) have shown increased plasma adiponectin.<ref name="pmid1639779">{{cite journal | vauthors = Grimshaw CE, Matthews DA, Varughese KI, Skinner M, Xuong NH, Bray T, Hoch J, Whiteley JM | title = Characterization and nucleotide binding properties of a mutant dihydropteridine reductase containing an aspartate 37-isoleucine replacement | journal = The Journal of Biological Chemistry | volume = 267 | issue = 22 | pages = 15334–9 | date = August 1992 | pmid = 1639779 | doi =  }}</ref> [[Curcumin]], [[capsaicin]], [[gingerol]], and [[catechin]]s have also been found to increase adiponectin expression.<ref name="pmid25110685">{{cite journal | vauthors = Nigro E, Scudiero O, Monaco ML, Palmieri A, Mazzarella G, Costagliola C, Bianco A, Daniele A | title = New insight into adiponectin role in obesity and obesity-related diseases | journal = BioMed Research International | volume = 2014 | issue =  | pages = 658913 | year = 2014 | pmid = 25110685 | pmc = 4109424 | doi = 10.1155/2014/658913 }}</ref>


==Metabolic effects==
Phylogenetic distribution includes expression in birds<ref name="pmid16276104">{{cite journal | vauthors = Yuan J, Liu W, Liu ZL, Li N | title = cDNA cloning, genomic structure, chromosomal mapping and expression analysis of ADIPOQ (adiponectin) in chicken | journal = Cytogenetic and Genome Research | volume = 112 | issue = 1-2 | pages = 148–51 | year = 2006 | pmid = 16276104 | doi = 10.1159/000087527 }}</ref> and fish.<ref name="pmid18489000">{{cite journal | vauthors = Nishio S, Gibert Y, Bernard L, Brunet F, Triqueneaux G, Laudet V | title = Adiponectin and adiponectin receptor genes are coexpressed during zebrafish embryogenesis and regulated by food deprivation | journal = Developmental Dynamics | volume = 237 | issue = 6 | pages = 1682–90 | date = June 2008 | pmid = 18489000 | doi = 10.1002/dvdy.21559 }}</ref>
Adiponectin affects:
 
== Metabolic==
 
'''Adiponectin effects:'''


* glucose flux
* glucose flux
** [[gluconeogenesis]]
** decreased [[gluconeogenesis]]
** [[glucose uptake]]
** increased [[glucose uptake]]<ref name="pmid12611609"/><ref name="pmid15544426"/><ref name="pmid12728641"/>
* lipid catabolism
* lipid catabolism<ref name="pmid12728641"/>
** [[β-oxidation]]
** [[β-oxidation]]<ref name="pmid15544426"/>
** triglyceride clearance
** [[triglyceride clearance]]<ref name="pmid15544426"/>
* [[endothelium|protection from endothelial dysfunction]]<!--Please change this when there is a proper Wikipage for Endothelial Dysfunction.--> (important facet of atherosclerotic formation)
* [[endothelium|protection from endothelial dysfunction]]<!--Please change this when there is a proper Wikipage for Endothelial Dysfunction.--> (important facet of atherosclerotic formation)
* [[insulin sensitivity]]
* [[insulin sensitivity]]
* weight loss
* weight loss
* control of energy metabolism.<ref name="pmid12728641"/>
* upregulation of [[uncoupling protein]]s <ref name="pmid17204560"/>
* reduction of TNF-alpha
'''Regulation of adiponectin'''
* Obesity is associated with decreased adiponectin.
**The exact mechanism of regulation is unknown, but adiponectin could be regulated by post-translational mechanisms in cells.<ref name="pmid22342903">{{cite journal | vauthors = Liu M, Liu F | title = Up- and down-regulation of adiponectin expression and multimerization: mechanisms and therapeutic implication | journal = Biochimie | volume = 94 | issue = 10 | pages = 2126–30 | date = October 2012 | pmid = 22342903 | pmc = 3542391 | doi = 10.1016/j.biochi.2012.01.008 }}</ref>
== Hypoadiponectinemia ==
A low level of adiponectin is an [[Independent variable|independent]] [[risk factor]] for developing:
*[[Metabolic syndrome]]<ref name="pmid19258676"/>
*[[Diabetes mellitus]]<ref name="pmid15544426"/><ref name="pmid17495599"/><ref name="pmid15794918"/><ref name="pmid15780820"/><ref name="pmid17112391"/>
== Other ==
Lower levels of adiponectin are associated with [[ADHD]] in adults.<ref name=Mavroconstanti_2014>{{cite journal | vauthors = Mavroconstanti T, Halmøy A, Haavik J | title = Decreased serum levels of adiponectin in adult attention deficit hyperactivity disorder | journal = Psychiatry Research | volume = 216 | issue = 1 | pages = 123–30 | date = April 2014 | pmid = 24559850 | doi = 10.1016/j.psychres.2014.01.025 }}</ref>
Adiponectin levels were found to be increased in [[rheumatoid arthritis]] patients responding to [[DMARD]]s or [[TNF inhibitor]] therapy.<ref name=" pmid = 24173909 ">{{cite journal | vauthors = Kim KS, Choi HM, Ji HI, Song R, Yang HI, Lee SK, Yoo MC, Park YB | title = Serum adipokine levels in rheumatoid arthritis patients and their contributions to the resistance to treatment | journal = Molecular Medicine Reports | volume = 9 | issue = 1 | pages = 255–60 | date = January 2014 | pmid = 24173909 | doi = 10.3892/mmr.2013.1764 | url = http://www.spandidos-publications.com/mmr/9/1/255 }}</ref>
Exercise induced release of adiponectin increased hippocampal growth and led to antidepressive symptoms in mice.<ref>{{cite journal | vauthors = Yau SY, Li A, Hoo RL, Ching YP, Christie BR, Lee TM, Xu A, So KF | title = Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 111 | issue = 44 | pages = 15810–5 | date = November 2014 | pmid = 25331877 | pmc = 4226125 | doi = 10.1073/pnas.1415219111 }}</ref>
=== As a drug target ===
Circulating levels of adiponectin can indirectly be increased through [[lifestyle modification]]s and certain drugs such as [[statin]]s.<ref>{{cite journal | vauthors = Lim S, Quon MJ, Koh KK | title = Modulation of adiponectin as a potential therapeutic strategy | journal = Atherosclerosis | volume = 233 | issue = 2 | pages = 721–8 | date = April 2014 | pmid = 24603219 | doi = 10.1016/j.atherosclerosis.2014.01.051 }}</ref>
A [[small molecule]] [[adiponectin receptor]] [[AdipoR1]] and [[AdipoR2]] [[agonist]], [[AdipoRon]], has been reported.<ref>{{cite journal | vauthors = Okada-Iwabu M, Yamauchi T, Iwabu M, Honma T, Hamagami K, Matsuda K, Yamaguchi M, Tanabe H, Kimura-Someya T, Shirouzu M, Ogata H, Tokuyama K, Ueki K, Nagano T, Tanaka A, Yokoyama S, Kadowaki T | title = A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity | journal = Nature | volume = 503 | issue = 7477 | pages = 493–9 | date = November 2013 | pmid = 24172895 | doi = 10.1038/nature12656 }}</ref> In 2016, the University of Tokyo announced it was launching an investigation into anonymously made claims of fabricated and falsified data on AdipoR1, AdipoR2, and AdipoRon<ref name="Dennis"/>.
Extracts of sweet potatoes have been reported to increase levels of adiponectin and thereby improve [[diabetes management|glycemic control]] in humans.<ref>{{cite journal | vauthors = Ludvik B, Hanefeld M, Pacini G | title = Improved metabolic control by Ipomoea batatas (Caiapo) is associated with increased adiponectin and decreased fibrinogen levels in type 2 diabetic subjects | journal = Diabetes, Obesity & Metabolism | volume = 10 | issue = 7 | pages = 586–92 | date = July 2008 | pmid = 17645559 | doi = 10.1111/j.1463-1326.2007.00752.x }}</ref> However, a systematic review concluded there is insufficient evidence to support the consumption of sweet potatoes to treat [[type 2 diabetes mellitus]].<ref>{{cite journal | vauthors = Ooi CP, Loke SC | title = Sweet potato for type 2 diabetes mellitus | journal = The Cochrane Database of Systematic Reviews | volume = 9 | issue = 9 | pages = CD009128 | date = September 2013 | pmid = 24000051 | doi = 10.1002/14651858.CD009128.pub3 }}</ref>
Adiponectin is apparently able to cross the [[blood-brain-barrier]].<ref name="pmid25331877">{{cite journal | vauthors = Yau SY, Li A, Hoo RL, Ching YP, Christie BR, Lee TM, Xu A, So KF | title = Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 111 | issue = 44 | pages = 15810–5 | date = November 2014 | pmid = 25331877 | pmc = 4226125 | doi = 10.1073/pnas.1415219111 }}</ref> However, conflicting data on this issue exist.<ref name="pmid16380487">{{cite journal | vauthors = Spranger J, Verma S, Göhring I, Bobbert T, Seifert J, Sindler AL, Pfeiffer A, Hileman SM, Tschöp M, Banks WA | title = Adiponectin does not cross the blood-brain barrier but modifies cytokine expression of brain endothelial cells | journal = Diabetes | volume = 55 | issue = 1 | pages = 141–7 | date = January 2006 | pmid = 16380487 | doi = 10.2337/diabetes.55.1.141 }}</ref> Adiponectin has a [[half-life]] of 2.5 hours in humans.<ref name="pmid15001639">{{cite journal | vauthors = Hoffstedt J, Arvidsson E, Sjölin E, Wåhlén K, Arner P | title = Adipose tissue adiponectin production and adiponectin serum concentration in human obesity and insulin resistance | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 89 | issue = 3 | pages = 1391–6 | date = March 2004 | pmid = 15001639 | doi = 10.1210/jc.2003-031458 }}</ref>


==Pharmaceutical therapy==
== References ==
Because adiponectin is a novel hormone, no therapy has yet been developed with adiponectin and it may be some years before [[clinical trial]]s commence. One obvious pharmaceutical treatment would be the administration of adiponectin; in mouse models such administration has shown positive effects. Problems to be overcome prior to human administration include establishing what the biologically active molecule is, what role [[post-translational modification]]s have upon the function and associated difficulties in generating biologically active molecules on a large scale. However, this remains a promising area of research for clinical therapy in diseases such as obesity, type 2 diabetes and fatty liver disease.
{{reflist|33em}}


==Further reading==
== External links ==
{{refbegin | 2}}
* {{UCSC gene info|ADIPOQ}}
{{PBB_Further_reading
| citations =
*{{cite journal  | author=Ukkola O, Santaniemi M |title=Adiponectin: a link between excess adiposity and associated comorbidities? |journal=J. Mol. Med. |volume=80 |issue= 11 |pages= 696-702 |year= 2003 |pmid= 12436346 |doi= 10.1007/s00109-002-0378-7 }}
*{{cite journal  | author=Díez JJ, Iglesias P |title=The role of the novel adipocyte-derived hormone adiponectin in human disease. |journal=Eur. J. Endocrinol. |volume=148 |issue= 3 |pages= 293-300 |year= 2003 |pmid= 12611609 |doi=  }}
*{{cite journal  | author=Vasseur F, Leprêtre F, Lacquemant C, Froguel P |title=The genetics of adiponectin. |journal=Curr. Diab. Rep. |volume=3 |issue= 2 |pages= 151-8 |year= 2003 |pmid= 12728641 |doi=  }}
*{{cite journal  | author=Matsuzawa Y, Funahashi T, Kihara S, Shimomura I |title=Adiponectin and metabolic syndrome. |journal=Arterioscler. Thromb. Vasc. Biol. |volume=24 |issue= 1 |pages= 29-33 |year= 2004 |pmid= 14551151 |doi= 10.1161/01.ATV.0000099786.99623.EF }}
*{{cite journal  | author=Nedvídková J, Smitka K, Kopský V, Hainer V |title=Adiponectin, an adipocyte-derived protein. |journal=Physiological research / Academia Scientiarum Bohemoslovaca |volume=54 |issue= 2 |pages= 133-40 |year= 2006 |pmid= 15544426 |doi=  }}
*{{cite journal  | author=Hug C, Lodish HF |title=The role of the adipocyte hormone adiponectin in cardiovascular disease. |journal=Current opinion in pharmacology |volume=5 |issue= 2 |pages= 129-34 |year= 2005 |pmid= 15780820 |doi= 10.1016/j.coph.2005.01.001 }}
*{{cite journal  | author=Hara K, Yamauchi T, Kadowaki T |title=Adiponectin: an adipokine linking adipocytes and type 2 diabetes in humans. |journal=Curr. Diab. Rep. |volume=5 |issue= 2 |pages= 136-40 |year= 2005 |pmid= 15794918 |doi=  }}
*{{cite journal  | author=Vasseur F, Meyre D, Froguel P |title=Adiponectin, type 2 diabetes and the metabolic syndrome: lessons from human genetic studies. |journal=Expert reviews in molecular medicine |volume=8 |issue= 27 |pages= 1-12 |year= 2007 |pmid= 17112391 |doi= 10.1017/S1462399406000147 }}
*{{cite journal  | author=Menzaghi C, Trischitta V, Doria A |title=Genetic influences of adiponectin on insulin resistance, type 2 diabetes, and cardiovascular disease. |journal=Diabetes |volume=56 |issue= 5 |pages= 1198-209 |year= 2007 |pmid= 17303804 |doi= 10.2337/db06-0506 }}
*{{cite journal  | author=Lara-Castro C, Fu Y, Chung BH, Garvey WT |title=Adiponectin and the metabolic syndrome: mechanisms mediating risk for metabolic and cardiovascular disease. |journal=Curr. Opin. Lipidol. |volume=18 |issue= 3 |pages= 263-70 |year= 2007 |pmid= 17495599 |doi= 10.1097/MOL.0b013e32814a645f }}
}}
{{refend}}


{{Hormones}}
{{Hormones}}
{{Signaling peptide/protein receptor modulators}}


[[Category:Adiponectin receptor agonists]]
[[Category:Peptide hormones]]
[[Category:Peptide hormones]]
[[Category:Proteins]]
[[Category:Proteins]]
[[Category:Obesity]]
[[Category:Obesity]]
[[Category:Endocrinology]]
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[[pl:Adiponektyna]]

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Adiponectin (also referred to as GBP-28, apM1, AdipoQ and Acrp30) is a protein hormone which is involved in regulating glucose levels as well as fatty acid breakdown. In humans it is encoded by the ADIPOQ gene and it is produced in adipose tissue.[1]

Structure

Adiponectin is a 244-amino-acid-long polypeptide (protein). There are four distinct regions of adiponectin. The first is a short signal sequence that targets the hormone for secretion outside the cell; next is a short region that varies between species; the third is a 65-amino acid region with similarity to collagenous proteins; the last is a globular domain. Overall this protein shows similarity to the complement 1Q factors (C1Q). However, when the 3-dimensional structure of the globular region was determined, a striking similarity to TNFα was observed, despite unrelated protein sequences.[2]

Function

Adiponectin is a protein hormone that modulates a number of metabolic processes, including glucose regulation and fatty acid oxidation.[3] Adiponectin is secreted from adipose tissue (and also from the placenta in pregnancy[4]) into the bloodstream and is very abundant in plasma relative to many hormones. Many studies have found adiponectin to be inversely correlated with body mass index in patient populations.[5] However, a meta analysis was not able to confirm this association in healthy adults.[6] Circulating adiponectin concentrations increase during caloric restriction in animals and humans, such as in patients with anorexia nervosa. This observation is surprising, given that adiponectin is produced by adipose tissue. However, a recent study suggests that adipose tissue within bone marrow, which increases during caloric restriction, contributes to elevated circulating adiponectin in this context.[7]

Transgenic mice with increased adiponectin show reduced adipocyte differentiation and increased energy expenditure associated with mitochondrial uncoupling.[8] The hormone plays a role in the suppression of the metabolic derangements that may result in type 2 diabetes,[5] obesity, atherosclerosis,[3] non-alcoholic fatty liver disease (NAFLD) and an independent risk factor for metabolic syndrome.[9] Adiponectin in combination with leptin has been shown to completely reverse insulin resistance in mice.[10]

Adiponectin is secreted into the bloodstream where it accounts for approximately 0.01% of all plasma protein at around 5-10 μg/mL (mg/L). In adults, plasma concentrations are higher in females than males, and are reduced in diabetics compared to non-diabetics. Weight reduction significantly increases circulating concentrations.[11]

Adiponectin automatically self-associates into larger structures. Initially, three adiponectin molecules bind together to form a homotrimer. The trimers continue to self-associate and form hexamers or dodecamers. Like the plasma concentration, the relative levels of the higher-order structures are sexually dimorphic, where females have increased proportions of the high-molecular weight forms. Recent studies showed that the high-molecular weight form may be the most biologically active form regarding glucose homeostasis.[12] High-molecular-weight adiponectin was further found to be associated with a lower risk of diabetes with similar magnitude of association as total adiponectin.[13] However, coronary artery disease has been found to be positively associated with high molecular weight adiponectin, but not with low molecular weight adiponectin.[14]

Adiponectin exerts some of its weight reduction effects via the brain. This is similar to the action of leptin,[15] but the two hormones perform complementary actions, and can have synergistic effects.[clarification needed]

Receptors

Main article: Adiponectin receptor

Adiponectin binds to a number of receptors. So far, two receptors have been identified with homology to G protein-coupled receptors, and one receptor similar to the cadherin family:[16][17]

These have distinct tissue specificities within the body and have different affinities to the various forms of adiponectin. The receptors affect the downstream target AMP kinase, an important cellular metabolic rate control point. Expression of the receptors is correlated with insulin levels, as well as reduced in mouse models of diabetes, particularly in skeletal muscle and adipose tissue.[18][19]. In 2016, the University of Tokyo announced it was launching an investigation into anonymously made claims of fabricated and falsified data on the identification of AdipoR1 and AdipoR2[20].

Discovery

Adiponectin was first characterised in 1995 in differentiating 3T3-L1 adipocytes (Scherer PE et al.).[21] In 1996 it was characterised in mice as the mRNA transcript most highly expressed in adipocytes[1]. In 2007, adiponectin was identified as a transcript highly expressed in preadipocytes[22] (precursors of fat cells) differentiating into adipocytes.[22][23]

The human homologue was identified as the most abundant transcript in adipose tissue. Contrary to expectations, despite being produced in adipose tissue, adiponectin was found to be decreased in obesity.[3][5][15] This downregulation has not been fully explained. The gene was localised to chromosome 3q27, a region highlighted as affecting genetic susceptibility to type 2 diabetes and obesity. Supplementation by differing forms of adiponectin was able to improve insulin control, blood glucose and triglyceride levels in mouse models.

The gene was investigated for variants that predispose to type 2 diabetes.[15][22][24][25][26][27] Several single nucleotide polymorphisms in the coding region and surrounding sequence were identified from several different populations, with varying prevalences, degrees of association and strength of effect on type 2 diabetes. Berberine, an isoquinoline alkaloid, has been shown to increase adiponectin expression[28] which partly explains its beneficial effects on metabolic disturbances. Mice fed the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have shown increased plasma adiponectin.[29] Curcumin, capsaicin, gingerol, and catechins have also been found to increase adiponectin expression.[30]

Phylogenetic distribution includes expression in birds[31] and fish.[32]

Metabolic

Adiponectin effects:

Regulation of adiponectin

  • Obesity is associated with decreased adiponectin.
    • The exact mechanism of regulation is unknown, but adiponectin could be regulated by post-translational mechanisms in cells.[33]

Hypoadiponectinemia

A low level of adiponectin is an independent risk factor for developing:

Other

Lower levels of adiponectin are associated with ADHD in adults.[34]

Adiponectin levels were found to be increased in rheumatoid arthritis patients responding to DMARDs or TNF inhibitor therapy.[35]

Exercise induced release of adiponectin increased hippocampal growth and led to antidepressive symptoms in mice.[36]

As a drug target

Circulating levels of adiponectin can indirectly be increased through lifestyle modifications and certain drugs such as statins.[37]

A small molecule adiponectin receptor AdipoR1 and AdipoR2 agonist, AdipoRon, has been reported.[38] In 2016, the University of Tokyo announced it was launching an investigation into anonymously made claims of fabricated and falsified data on AdipoR1, AdipoR2, and AdipoRon[20].

Extracts of sweet potatoes have been reported to increase levels of adiponectin and thereby improve glycemic control in humans.[39] However, a systematic review concluded there is insufficient evidence to support the consumption of sweet potatoes to treat type 2 diabetes mellitus.[40]

Adiponectin is apparently able to cross the blood-brain-barrier.[41] However, conflicting data on this issue exist.[42] Adiponectin has a half-life of 2.5 hours in humans.[43]

References

  1. ↑ 1.0 1.1 Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matsubara K (April 1996). "cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1)". Biochemical and Biophysical Research Communications. 221 (2): 286–9. doi:10.1006/bbrc.1996.0587. PMID 8619847.
  2. ↑ Shapiro L, Scherer PE (March 1998). "The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor". Current Biology. 8 (6): 335–8. doi:10.1016/S0960-9822(98)70133-2. PMID 9512423.
  3. ↑ 3.0 3.1 3.2 3.3 Díez JJ, Iglesias P (March 2003). "The role of the novel adipocyte-derived hormone adiponectin in human disease". European Journal of Endocrinology. 148 (3): 293–300. doi:10.1530/eje.0.1480293. PMID 12611609.
  4. ↑ Chen J, Tan B, Karteris E, Zervou S, Digby J, Hillhouse EW, Vatish M, Randeva HS (June 2006). "Secretion of adiponectin by human placenta: differential modulation of adiponectin and its receptors by cytokines". Diabetologia. 49 (6): 1292–302. doi:10.1007/s00125-006-0194-7. PMID 16570162.
  5. ↑ 5.0 5.1 5.2 Ukkola O, Santaniemi M (November 2002). "Adiponectin: a link between excess adiposity and associated comorbidities?". Journal of Molecular Medicine. 80 (11): 696–702. doi:10.1007/s00109-002-0378-7. PMID 12436346.
  6. ↑ Kuo SM, Halpern MM (December 2011). "Lack of association between body mass index and plasma adiponectin levels in healthy adults". International Journal of Obesity. 35 (12): 1487–94. doi:10.1038/ijo.2011.20. PMID 21364526.
  7. ↑ Cawthorn WP, Scheller EL, Learman BS, Parlee SD, Simon BR, Mori H, Ning X, Bree AJ, Schell B, Broome DT, Soliman SS, DelProposto JL, Lumeng CN, Mitra A, Pandit SV, Gallagher KA, Miller JD, Krishnan V, Hui SK, Bredella MA, Fazeli PK, Klibanski A, Horowitz MC, Rosen CJ, MacDougald OA (August 2014). "Bone marrow adipose tissue is an endocrine organ that contributes to increased circulating adiponectin during caloric restriction". Cell Metabolism. 20 (2): 368–75. doi:10.1016/j.cmet.2014.06.003. PMC 4126847. PMID 24998914.
  8. ↑ 8.0 8.1 Bauche IB, El Mkadem SA, Pottier AM, Senou M, Many MC, Rezsohazy R, Penicaud L, Maeda N, Funahashi T, Brichard SM (April 2007). "Overexpression of adiponectin targeted to adipose tissue in transgenic mice: impaired adipocyte differentiation". Endocrinology. 148 (4): 1539–49. doi:10.1210/en.2006-0838. PMID 17204560.
  9. ↑ 9.0 9.1 Renaldi O, Pramono B, Sinorita H, Purnomo LB, Asdie RH, Asdie AH (January 2009). "Hypoadiponectinemia: a risk factor for metabolic syndrome". Acta Medica Indonesiana. 41 (1): 20–4. PMID 19258676.
  10. ↑ Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T (August 2001). "The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity". Nature Medicine. 7 (8): 941–6. doi:10.1038/90984. PMID 11479627.
  11. ↑ Coppola A, Marfella R, Coppola L, Tagliamonte E, Fontana D, Liguori E, Cirillo T, Cafiero M, Natale S, Astarita C (May 2009). "Effect of weight loss on coronary circulation and adiponectin levels in obese women". International Journal of Cardiology. 134 (3): 414–6. doi:10.1016/j.ijcard.2007.12.087. PMID 18378021.
  12. ↑ Oh DK, Ciaraldi T, Henry RR (May 2007). "Adiponectin in health and disease". Diabetes, Obesity & Metabolism. 9 (3): 282–9. doi:10.1111/j.1463-1326.2006.00610.x. PMID 17391153.
  13. ↑ Zhu N, Pankow JS, Ballantyne CM, Couper D, Hoogeveen RC, Pereira M, Duncan BB, Schmidt MI (November 2010). "High-molecular-weight adiponectin and the risk of type 2 diabetes in the ARIC study". The Journal of Clinical Endocrinology and Metabolism. 95 (11): 5097–104. doi:10.1210/jc.2010-0716. PMC 2968724. PMID 20719834.
  14. ↑ Rizza S, Gigli F, Galli A, Micchelini B, Lauro D, Lauro R, Federici M (April 2010). "Adiponectin isoforms in elderly patients with or without coronary artery disease". Journal of the American Geriatrics Society. 58 (4): 702–6. doi:10.1111/j.1532-5415.2010.02773.x. PMID 20398150.
  15. ↑ 15.0 15.1 15.2 15.3 15.4 15.5 15.6 Nedvídková J, Smitka K, Kopský V, Hainer V (2005). "Adiponectin, an adipocyte-derived protein" (PDF). Physiological Research. 54 (2): 133–40. PMID 15544426.
  16. ↑ Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekawa S, Waki H, Tsuno NH, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu T, Nagai R, Kadowaki T (June 2003). "Cloning of adiponectin receptors that mediate antidiabetic metabolic effects". Nature. 423 (6941): 762–9. doi:10.1038/nature01705. PMID 12802337.
  17. ↑ Hug C, Wang J, Ahmad NS, Bogan JS, Tsao TS, Lodish HF (July 2004). "T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin". Proceedings of the National Academy of Sciences of the United States of America. 101 (28): 10308–13. doi:10.1073/pnas.0403382101. PMC 478568. PMID 15210937.
  18. ↑ Fang X, Sweeney G (November 2006). "Mechanisms regulating energy metabolism by adiponectin in obesity and diabetes". Biochemical Society Transactions. 34 (Pt 5): 798–801. doi:10.1042/BST0340798. PMID 17052201.
  19. ↑ Bonnard C, Durand A, Vidal H, Rieusset J (February 2008). "Changes in adiponectin, its receptors and AMPK activity in tissues of diet-induced diabetic mice". Diabetes & Metabolism. 34 (1): 52–61. doi:10.1016/j.diabet.2007.09.006. PMID 18222103.
  20. ↑ 20.0 20.1 University of Tokyo to investigate data manipulation charges against six prominent research groups ScienceInsider, Dennis Normile, Sep 20, 2016
  21. ↑ Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF (November 1995). "A novel serum protein similar to C1q, produced exclusively in adipocytes". The Journal of Biological Chemistry. 270 (45): 26746–9. doi:10.1074/jbc.270.45.26746. PMID 7592907.
  22. ↑ 22.0 22.1 22.2 22.3 Lara-Castro C, Fu Y, Chung BH, Garvey WT (June 2007). "Adiponectin and the metabolic syndrome: mechanisms mediating risk for metabolic and cardiovascular disease". Current Opinion in Lipidology. 18 (3): 263–70. doi:10.1097/MOL.0b013e32814a645f. PMID 17495599.
  23. ↑ Matsuzawa Y, Funahashi T, Kihara S, Shimomura I (January 2004). "Adiponectin and metabolic syndrome". Arteriosclerosis, Thrombosis, and Vascular Biology. 24 (1): 29–33. doi:10.1161/01.ATV.0000099786.99623.EF. PMID 14551151.
  24. ↑ 24.0 24.1 Hara K, Yamauchi T, Kadowaki T (April 2005). "Adiponectin: an adipokine linking adipocytes and type 2 diabetes in humans". Current Diabetes Reports. 5 (2): 136–40. doi:10.1007/s11892-005-0041-0. PMID 15794918.
  25. ↑ 25.0 25.1 25.2 25.3 Vasseur F, Leprêtre F, Lacquemant C, Froguel P (April 2003). "The genetics of adiponectin". Current Diabetes Reports. 3 (2): 151–8. doi:10.1007/s11892-003-0039-4. PMID 12728641.
  26. ↑ 26.0 26.1 Hug C, Lodish HF (April 2005). "The role of the adipocyte hormone adiponectin in cardiovascular disease". Current Opinion in Pharmacology. 5 (2): 129–34. doi:10.1016/j.coph.2005.01.001. PMID 15780820.
  27. ↑ 27.0 27.1 Vasseur F, Meyre D, Froguel P (November 2006). "Adiponectin, type 2 diabetes and the metabolic syndrome: lessons from human genetic studies". Expert Reviews in Molecular Medicine. 8 (27): 1–12. doi:10.1017/S1462399406000147. PMID 17112391.
  28. ↑ Choi BH, Kim YH, Ahn IS, Ha JH, Byun JM, Do MS (2009). "The inhibition of inflammatory molecule expression on 3T3-L1 adipocytes by berberine is not mediated by leptin signaling". Nutrition Research and Practice. 3 (2): 84–8. doi:10.4162/nrp.2009.3.2.84. PMC 2788178. PMID 20016706.
  29. ↑ Grimshaw CE, Matthews DA, Varughese KI, Skinner M, Xuong NH, Bray T, Hoch J, Whiteley JM (August 1992). "Characterization and nucleotide binding properties of a mutant dihydropteridine reductase containing an aspartate 37-isoleucine replacement". The Journal of Biological Chemistry. 267 (22): 15334–9. PMID 1639779.
  30. ↑ Nigro E, Scudiero O, Monaco ML, Palmieri A, Mazzarella G, Costagliola C, Bianco A, Daniele A (2014). "New insight into adiponectin role in obesity and obesity-related diseases". BioMed Research International. 2014: 658913. doi:10.1155/2014/658913. PMC 4109424. PMID 25110685.
  31. ↑ Yuan J, Liu W, Liu ZL, Li N (2006). "cDNA cloning, genomic structure, chromosomal mapping and expression analysis of ADIPOQ (adiponectin) in chicken". Cytogenetic and Genome Research. 112 (1–2): 148–51. doi:10.1159/000087527. PMID 16276104.
  32. ↑ Nishio S, Gibert Y, Bernard L, Brunet F, Triqueneaux G, Laudet V (June 2008). "Adiponectin and adiponectin receptor genes are coexpressed during zebrafish embryogenesis and regulated by food deprivation". Developmental Dynamics. 237 (6): 1682–90. doi:10.1002/dvdy.21559. PMID 18489000.
  33. ↑ Liu M, Liu F (October 2012). "Up- and down-regulation of adiponectin expression and multimerization: mechanisms and therapeutic implication". Biochimie. 94 (10): 2126–30. doi:10.1016/j.biochi.2012.01.008. PMC 3542391. PMID 22342903.
  34. ↑ Mavroconstanti T, Halmøy A, Haavik J (April 2014). "Decreased serum levels of adiponectin in adult attention deficit hyperactivity disorder". Psychiatry Research. 216 (1): 123–30. doi:10.1016/j.psychres.2014.01.025. PMID 24559850.
  35. ↑ Kim KS, Choi HM, Ji HI, Song R, Yang HI, Lee SK, Yoo MC, Park YB (January 2014). "Serum adipokine levels in rheumatoid arthritis patients and their contributions to the resistance to treatment". Molecular Medicine Reports. 9 (1): 255–60. doi:10.3892/mmr.2013.1764. PMID 24173909.
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