Pilot: How the Liver Tells Time on High-Fat Diet: Pathway to Obesity

Grants and Contracts Details

Description

The circadian and metabolic systems functionally interact, such that the circadian system optimally tunes metabolic processes to daily environmental cycles. To investigate the tuning of rhythmic metabolic processes and how they are altered in diet-induced obesity, we have developed an acute model for assessing the effects of high-fat diet on the daily rhythms of mice. Using this model, we have shown that after only one week of high-fat diet consumption, the timing of the circadian clock in the liver is robustly advanced, but the timing in other tissues is not altered, in male mice that develop diet-induced obesity. In constrast, high-fat feeding does not affect the liver circadian clock in female mice that are resistant to dietinduced obesity. The overall goal of this study is to utilize this acute model and leverage the sex difference in responsivenss of the liver clock to examine how this shift in the timing of the liver rhythm contributes to diet-induced obesity in males. Since the liver is a key organ in insulin-mediated regulation of metabolism, we will rigorously test the hypothesis that rhythmic insulin action in the liver is acutely altered by high-fat diet in males, but not females. Specifically, we will quantify daily rhythms of hepatic insulin action (Aim 1) and test the hypothesis that high-fat diet consumption acutely alters the timing of the responsiveness of the liver to insulin in male mice (Aim 2). With the pilot data obtained in this proposal, future studies will further investigate the metabolic implications of high-fat diet-induced disruption of the liver clock.
StatusFinished
Effective start/end date2/23/1311/30/21

Funding

  • Washington University in St. Louis

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