Obesity in mice with adipocyte-specific deletion of clock component Arntl

Nat Med. 2012 Dec;18(12):1768-77. doi: 10.1038/nm.2979. Epub 2012 Nov 11.


Adipocytes store excess energy in the form of triglycerides and signal the levels of stored energy to the brain. Here we show that adipocyte-specific deletion of Arntl (also known as Bmal1), a gene encoding a core molecular clock component, results in obesity in mice with a shift in the diurnal rhythm of food intake, a result that is not seen when the gene is disrupted in hepatocytes or pancreatic islets. Changes in the expression of hypothalamic neuropeptides that regulate appetite are consistent with feedback from the adipocyte to the central nervous system to time feeding behavior. Ablation of the adipocyte clock is associated with a reduced number of polyunsaturated fatty acids in adipocyte triglycerides. This difference between mutant and wild-type mice is reflected in the circulating concentrations of polyunsaturated fatty acids and nonesterified polyunsaturated fatty acids in hypothalamic neurons that regulate food intake. Thus, this study reveals a role for the adipocyte clock in the temporal organization of energy regulation, highlights timing as a modulator of the adipocyte-hypothalamic axis and shows the impact of timing of food intake on body weight.

Publication types

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

MeSH terms

  • ARNTL Transcription Factors / deficiency*
  • ARNTL Transcription Factors / genetics
  • Absorptiometry, Photon
  • Adipocytes / metabolism*
  • Animals
  • Appetite Regulation / genetics*
  • Appetite Regulation / physiology
  • Blotting, Western
  • Calorimetry
  • Chromatin Immunoprecipitation
  • Chromatography, Liquid
  • Circadian Rhythm / physiology*
  • DNA Primers / genetics
  • Discriminant Analysis
  • Energy Metabolism / genetics
  • Energy Metabolism / physiology*
  • Fatty Acids, Unsaturated / metabolism
  • Gene Deletion
  • Histological Techniques
  • Hypothalamus / metabolism
  • Mass Spectrometry
  • Mice
  • Neuropeptides / metabolism
  • Obesity / genetics*
  • Protein Array Analysis
  • Real-Time Polymerase Chain Reaction
  • Statistics, Nonparametric


  • ARNTL Transcription Factors
  • Arntl protein, mouse
  • DNA Primers
  • Fatty Acids, Unsaturated
  • Neuropeptides