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Feeding regulation by ASB4

ASB4 的饲喂调节

基本信息

批准号：
10886884
负责人：
Allison W Xu
金额：
$ 16.15万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10886884
关键词：
ART protein Acute Amino Acid Sequence Animals Ankyrin Repeat Appetite Depressants Area Attenuated Binding Binge Eating Body Weight Brain Calcitonin Calcitonin Receptor Cells Cephalic Consumption Down-Regulation Eating Evolution Fasting Feeding Patterns Food Food deprivation (experimental)Gene Targeting Genes Genetic Goals Health Human Hyperphagia Hypothalamic structure IRS4 gene Injections Intermittent fasting Leptin Leptin deficiency Ligands Link Mediating Metabolic Metabolic Control Metabolic hormone Metabolism Mus Neurons Non-Insulin-Dependent Diabetes Mellitus Nutritional status Obesity Opsin Persons Phenotype Photophobia Play Prosencephalon Protein Deficiency Regulation Resistance Role Salmon Satiation Structure of nucleus infundibularis hypothalami Surveys Weight maintenance regimen cell type cognitive function coping energy balance feeding gene environment interaction genetic variant genome wide association study hindbrain improved insight knock-down novel obesity development optogenetics sex ubiquitin-protein ligase

项目摘要

Project Summary/Abstract The genetic basis of most common forms of obesity is polygenic, highlighting the importance of interactions among different genetic variants in body weight regulation. Indeed, large-scale GWAS studies have identified increasing number of genetic variants that are associated with human obesity. Despite these advances, the metabolic functions of these genetic variants and how they interact with key regulators of energy balance are still poorly understood. We recently identified Ankyrin Repeat and SOCS Box Containing 4 (ASB4), a gene that is linked to human obesity by multiple GWAS studies, as an important regulator of satiety especially after period of food deprivation. Expression of Asb4 is modulated by nutritional status, being responsive to leptin and agouti-related protein in a reciprocal fashion, allowing ASB4 to sense changes of body’s energy reserve. We show that ASB4 deficiency leads to increased meal size and food intake during periods of intense feeding, such as refeeding. We also show that ASB4 is required for the expression of calcitonin receptor (CalcR) and the anorectic effects of salmon calcitonin, a potent ligand for CalcR. Together, these findings strongly indicate that ASB4 is important for metabolic control in humans and mice, and that it is an important regulator of meal size. The goal of this R01 application is to determine the mechanisms by which ASB4 exerts its metabolic effects. We will identify ASB4 neuronal subpopulations that control meal size and food intake. We will evaluate if importance of ASB4 in satiety control manifests under intermittent fasting, a feeding pattern that promotes consumption of large meals. As ASB4 is highly conserved between mice and humans and is linked to obesity by GWAS studies, this study will provide mechanistic insight into how ASB4 may regulate meal size and food intake in humans.

项目总结/文摘