SIRT1 in the Ventromedial Hypothalamus: A Nutrient Sensor Input Into the Internal Timekeeper.

Abstract

There was a time when talking about clocks, rhythms, and timing of meals led to glazed eyes from colleagues in the field of diabetes and obesity (“diabesity”). The main focus at the turn of this century was on using newly developed molecular techniques to interrogate form and function of neural circuits linked to the control of appetite and metabolism. The problem of obesity and the metabolic conditions associated with nutrient excess facing most nations was, and likely still is by most, primarily viewed as a failure to coordinate energy consumption and energy expenditure (“energy homeostasis”). However, the publication in Science in 2005 of an obese phenotype in mice carrying the Δ19 mutation in the Circadian Locomotor Output Cycles Kaput (Clock) gene was important for bringing what is essentially an old idea back into the consciousness of those interested in how weight and metabolic health are maintained (1).