GSE104709
Isolating Independent Effects of Diet/Energy Balance and Body Weight on Behavior and Metabolic Health
Associated with numerous metabolic and behavioral abnormalities, obesity is classified by metrics reliant on body weight (such as body mass index). However, overnutrition is the common cause of obesity, and may independently contribute to these obesity-related abnormalities.  The goal of this study is to isolate 'diet/energy balance' effects independent from 'body weight' effects on various metabolic and behavioral parameters using the Diet Switch feeding paradigm in mice. [We conducted] unbiased gene expression analysis of the nutrient-sensing circumventricular hypothalamus [using RNA-seq]. Remarkably, only two genes responded to diet/energy balance (neuropeptide y [npy] and agouti-related peptide [agrp]), while others were related only to body weight. Furthermore, linear regression models revealed that npy and agrp showed similar modifiability by diet/energy balance and body weight compared to electroencephalographic-measured sleep/wake behavior. Overall design: Purified polyA-enriched mRNA from circumventricular hypothalamus (CVH) punches in mice under various dietary conditions: 1) Regular chow (RC) only (n=5); 2) High-fat diet (HFD) only (n=5); 3) Chornic RC followed by acute HFD (RC.HFD; n=6); 4) Chronic HFD follwed by acute RC (HFD.RC; n=5)