Renin: who needs it, anyway?

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December 18, 2007 By Benjamin A. Olenchock, M.D. Ph.D. [1]

Chapel Hill

Medicines that interrupt the renin-angiotensin-aldosterone axis have been a major advance in the medical management of heart disease, kidney disease, and diabetes. The indications for ACE-inhibitors and ARBs seem to grow daily, and they are many physicians’ first choice anti-hypertensive medicine. ACE inhibitors are known to increase insulin sensitivity in addition to their renal protective and anti-hypertensive effects. Aliskerin, the first direct renin inhibitor, will likely extend our ability to interrupt this hormonal axis. A new study has examined the metabolic consequences of genetic loss of renin in mice.

Previous work had demonstrated that mice deficient in renin have lower blood pressure than wild-type mice. The new studies demonstrate that they also weigh less than their wild-type littermates, have less body fat, and do not gain weight when fed a high fat diet. Following a glucose challenge, they secrete less insulin than wild-type mice with similar plasma glucose control. They eat a similar amount of calories, but waste fat in their stools and have higher basal energy expenditure. The dietary fat wasting might be due to deficiency in a pancreatic lipase and co-lipase, and the increased metabolic rate might be due to deficiency in an enzyme involved in triglyceride synthesis, leading to increased fatty acid oxidation. Interestingly, all of the metabolic effects of renin deficiency are overcome by low-dose angiotenin II, suggesting that the angiotensin-independent effects of renin on metabolism are minimal.

Renin-deficient mice are lean, insulin-sensitive and are resistant to diet-induced obesity without having to expend more energy. As Aliskerin gains a larger share of the anti-hypertensive market, let’s hope people behave like mice.

Increased energy expenditure, dietary fat wasting, and resistance to diet-induced obesity in mice lacking Renin. Cell Metab. 2007 Dec;6(6):506-12.