SIRT3 weighs heavily in the metabolic balance: a new role for SIRT3 in metabolic syndrome

The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Michelle F Green, Matthew D Hirschey

Abstract

Eating a "Western diet" high in fat and sugars is associated with accelerated development of age-related metabolic diseases such as obesity, insulin resistance, and diabetes while incidences of these diseases are decreased on a low-calorie diet. The mitochondrial NAD(+)-dependent protein deacetylase SIRT3 has previously been shown to be important in adapting to metabolic stress brought on by fasting and calorie restriction. During times of metabolic stress, SIRT3 is upregulated and maintains homeostasis following nutrient deprivation by turning on pathways such as fatty acid oxidation, antioxidant production, and the urea cycle. New studies now demonstrate that SIRT3 is regulated during nutrient excess. During high-fat diet feeding, SIRT3 is downregulated leading to mitochondrial protein hyperacetylation. The consequence of this hyperacetylation is the accelerated development of metabolic syndrome. Thus, SIRT3 is emerging as an important metabolic sensor working to restore metabolic homeostasis during times of stress.

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Citations

Apr 23, 2013·Human Genetics·Todd L EdwardsDigna R Velez Edwards
Sep 18, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Melissa A SuterKjersti M Aagaard
Aug 16, 2013·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Jie SongChao-Yu Miao
Oct 13, 2015·Metabolism: Clinical and Experimental·Brian A PedersenPing H Wang
Apr 27, 2013·The FEBS Journal·Christian DölleMathias Ziegler
Dec 9, 2014·The Journal of Nutritional Biochemistry·Kate J ClaycombeW Thomas Johnson
Nov 23, 2013·Medicine and Science in Sports and Exercise·Justin A FletcherR Scott Rector
Jul 6, 2014·Physiological Reviews·Dmitry B ZorovSteven J Sollott
Dec 31, 2015·Current Opinion in Nephrology and Hypertension·Sergey I Dikalov, Anna E Dikalova
Dec 24, 2013·American Journal of Physiology. Heart and Circulatory Physiology·Heng ZengJian-Xiong Chen
May 16, 2019·Journal of Obesity & Metabolic Syndrome·Eunyoung HaTae Kyung Ha

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