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

Abstract

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.

Rhythmicity of the intestinal microbiota is regulated by gender and the host circadian clock

“…Fasting is associated with Bacteroidetes dominance and ingestion of food with a proportional increase of Firmicutes (11,12). Mice are active in the dark phase and consume the majority of their food during the first several hours of the dark phase (27). Therefore, during the daytime, when the mice are resting and consuming less food, Bacteroidetes are predominant, reaching the highest abundance toward the end of the light phase.…”

Lipidomics reveals diurnal lipid oscillations in human skeletal muscle persisting in cellular myotubes cultured in vitro

“…circadian rhythmicity is associated with hyperlipidemia and hepatic steatosis in ClockΔ19 mice (13), with obesity in mice that bear an adipocyte-specific deletion of Bmal1 (14), and with reduced wholebody weight and reduction of total triglycerides and fatty acids in blood plasma of Per2-deficient mice (15).…”

Horloges circadiennes et métabolisme : intégration des signaux métaboliques et environnementaux

“…Par exemple, le miARN122, qui est sous le contrôle direct de Rev-erb, présente une expression rythmique dans le foie de souris où il régule en retour de nombreux gènes impliqués dans le métabolisme [2,3]. Des modifications épigénétiques interviennent également dans [12], tandis qu'une délétion spécifiquement dans le pancréas induit une hypo-insulinémie [13]. Par ailleurs, une délétion de bmal1 spéci-fiquement dans le foie entraîne une hypoglycémie durant la phase de repos, une augmentation de la clairance du glucose et des altérations du rythme circadien des gènes du métabolisme hépatique du glucose [14].…”