Satiety signaling in Caenorhabditis elegans

Ut Southwestern Medical Center, Dallas TX

Investigators

Linked publications & trials

Abstract

[unreadable] DESCRIPTION (provided by applicant): [unreadable] In humans, uncontrolled appetite and subsequent overeating cause obesity and obesity-associated diseases. Appetite is controlled in part by satiety signals that prevent the consumption of unneeded food. C. elegans may also be subject to satiety: feeding motions and exploratory behavior are reduced when worms are starved for 24 hours, then refed for 6 hours. This study aims to define C. elegans satiety signals that control appetite by identifying and characterizing the components of the pathway via a genetic screen. The hypotheses to be tested are (1) that worms induced to consume excess food become satiated, and (2) that satiety influences behavior via a specific molecular pathway or pathways. These hypotheses will be tested through 3 specific aims; Aim 1: Characterize the behavioral mechanisms of satiety. Subaim 1: Using insatiable mutations which are defective in feeding or nutrient absorption, we will determine whether reduction of feeding motions and locomotive activity in starved/refed worms are direct reflections of their satiety status. Subaim 2: Using different low and high-quality food sources, we will manipulate the conditions of satiety and examine whether feeding motions and.locomotive activity depend on food quality. Aim 2: Identify mutants that are defective in satiety behavior. Through genetic screening for mutants that have increased feeding motions and locomotive activity compared to wild type after starvation/refeeding, components of the satiety signaling pathway will be identified. Aim 3: Test candidate satiety signals. Cholecystokinin and peptide YY decrease meal size when exogenously administered to mice. We will target homologs of receptors for these neuropeptides by reverse genetic methods such as RNA interference. We will examine whether the knockout or overexpression of candidate receptors increases or decreases meal size [unreadable] [unreadable]