Circadian disruption in the pathogenesis of metabolic syndrome

Diabetes Metab. 2014 Nov;40(5):338-46. doi: 10.1016/j.diabet.2013.12.005. Epub 2014 Jan 14.

Abstract

Metabolic syndrome is a multifactorial process induced by a combination of genetic and environmental factors and recent evidence has highlighted that circadian disruption and sleep loss contribute to disease pathogenesis. Emerging work in experimental genetic models has provided insight into the mechanistic basis for clock disruption in disease. Indeed, disruption of the clock system perturbs both neuroendocrine pathways within the hypothalamus important in feeding and energetics, in addition to peripheral tissues involved in glucose and lipid metabolism. This review illustrates the impact of molecular clock disruptions at the level of both brain and behavior and peripheral tissues, with a focus on how such dysregulation in turn impacts lipid and glucose homeostasis, inflammation and cardiovascular function. New insight into circadian biology may ultimately lead to improved therapeutics for metabolic syndrome and cardiovascular disease in humans.

Keywords: Cardiovascular disease; Circadian rhythm; Metabolism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • CLOCK Proteins / metabolism*
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / physiopathology*
  • Circadian Rhythm
  • Energy Metabolism
  • Gene Expression Regulation
  • Glucose / metabolism
  • Homeostasis
  • Humans
  • Hypothalamus / metabolism
  • Inflammation / metabolism
  • Inflammation / physiopathology*
  • Lipid Metabolism*
  • Lipids / blood
  • Metabolic Syndrome / metabolism
  • Metabolic Syndrome / physiopathology*
  • Signal Transduction
  • Sleep Deprivation / metabolism
  • Sleep Deprivation / physiopathology*

Substances

  • Lipids
  • CLOCK Proteins
  • Glucose