MMPC :: MICROMouse Program Application Abstract

MICROMouse Program Application Abstract

MMPC Funded Abstracts

MICROMouse

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Interplay between circadian disorganization and obesity

Shin Yamazaki (Dallas, TX)

MICROMouse Program

Obesity is reaching epidemic proportions and is clearly recognized as a serious worldwide threat to human health. Studies have shown that individuals who do not eat breakfast or patients with night eating syndrome have significantly higher body mass indices than people whose food intake is concentrated during the daytime. In addition, when high-fat food is provided to mice only during their inactive period, they gain significantly more weight than mice that eat during their active time. Temporal processes, such as the timing of food intake, are controlled by circadian clocks, which produce self-sustained oscillations in physiology and behavior with endogenous periods of approximately 24 hours that can be synchronized to environmental cues such as the light-dark cycle and food availability. Circadian clocks are present in the brain and in peripheral tissues and their rhythms are coordinated by a master clock in the hypothalamus. These clocks acquire a specific phase relationship with each other that optimally coordinates behavior and physiology with environmental cycles of light/dark and fasting/feeding. Distortion of the phase relationship between these clocks by jet-lag and shift work results in increased risk for obesity and metabolic disorder. The interplay between daily feeding rhythms and circadian disorganization are poorly understood as they relate to metabolic dysfunction. The circadian gene, Period3 (Per3), plays an important role in conferring proper energy balance because Per3 knockout mice develop a potentiated diet-induced obese phenotype compared to wild-type mice. In addition, our preliminary studies show that circadian phase organization of Per3 knockout mice is drastically altered, with notable distortion in tissues related to metabolic function. Therefore, Per3 knockout mice are a distinctive animal model of obesity that provides the unique opportunity to investigate the interplay between eating patterns and circadian organization. The overall goal of this proposal is to test the hypothesis that aberrant feeding rhythms and circadian disorganization lead to uncoordinated metabolic processes and obesity. In Per3 knockout mice, we hypothesize that (i) aberrant eating patterns contribute to circadian disorganization, (ii) circadian disorganization has functional consequences including alterations in the daily rhythms of hormones important for energy balance, and (iii) manipulation of aberrant eating patterns can correct body weight and misalignment of circadian clocks.

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