Mitochondrial uncoupling regulates heat production in cells by preventing energy produced by the electron transport chain from being directed to the production of adenosine triphosphate, an energy store molecule used to power cellular operations. Modestly increased uncoupling mimics some of the benefits of calorie restriction, meaning improved cell function, health, and life span. Greatly increased uncoupling is fatal, due to excessive heat production. Therein lies the challenge when it comes to the production of drugs that can induce mitochondrial uncoupling. Some progress has been made in recent years regarding strategies that lead to safe mitochondrial uncoupling drugs, and there are now a few drug candidates with published data in addition to the one described here.
Obesity, nonalcoholic fatty liver disease (NAFLD), and insulin resistance (IR) associated with visceral, hepatic, or ectopic fat are major risk factors for a number of chronic diseases including diabetes mellitus (DM), cardiovascular diseases, and cancer. These metabolic disorders are intrinsically involved in an energy imbalance between energy expenditure and calorie intake. An appropriate degree of calorie restriction (CR) ameliorates these disorders, and moreover, it is the only proven way to extend
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