Editors' ChoiceMetabolism

ACEing Lipid Metabolism

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Science Signaling  13 May 2008:
Vol. 1, Issue 19, pp. ec177
DOI: 10.1126/stke.119ec177

The renin-angiotensin system (RAS) regulates blood volume and pressure through the peptide hormones angiotensin II and bradykinin, which have opposing functions as a vasoconstrictor and vasodilator, respectively. Increased production of angiotensin 2 has also been linked to increased fat accumulation in both humans and rodents. Jayasooriya et al. report phenotypic analyses of mice that lack angiotensin-converting enzyme (ACE), which both degrades bradykinin and produces angiotensin II from its biologically inactive precursor angiotensin I. ACE knockout (ACE–/–) mice weighed less and had less abdominal fat than their wild-type control littermates, yet they were not more physically active, did not eat any less food, and did not secrete more fat in their waste. ACE–/– animals cleared glucose from their blood faster than controls, and respiration measurements indicated that they also expended more energy regardless of their activity level or food consumption. Quantitative PCR analysis revealed that genes required for lipid metabolism were more highly expressed in the livers of ACE–/– animals, so it appeared that ACE–/– mice metabolized fat faster than normal mice. The authors hypothesized that the increased fat metabolism was mediated by the decrease in angiotensin II activity, because mice that produce lower-than-normal amounts of angiotensin II have similar phenotypes. The glucose clearance phenotype, however, could not be readily explained, but the authors speculated that vasodilation induced by the increase in circulating bradykinin in ACE–/– mice may have increased the rate at which glucose is cleared from the blood by delivering it to tissues faster. The authors conclude that the previously recognized role of RAS in regulating body fat accumulation is mediated by controlling the rate of metabolism rather than that of adipose tissue formation.

A. P. Jayasooriya, M. L. Mathai, L. L. Walker, D. P. Begg, D. A. Denton, D. Cameron-Smith, G. F. Egan, M. J. McKinley, P. D. Rodger, A. J. Sinclair, J. D. Wark, H. S. Weisinger, M. Jois, R. S. Weisinger, Mice lacking angiotensin-converting enzyme have increased energy expenditure, with reduced fat mass and improved glucose clearance. Proc. Natl. Acad. Sci. U.S.A. 105, 6531-6536 (2008). [Abstract] [Full Text]