Date of Award
Spring 2023
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Cellular and Molecular Physiology
First Advisor
Yang, Xiaoyong
Abstract
The central nervous system plays a vital role in the homeostatic control of body weight and metabolism. Among brain nuclei, the ventromedial hypothalamus (VMH) is an important hypothalamic nucleus known to regulate body weight, energy balance, and counterregulatory response. However, the pathways for VMH neurons to regulate lipid metabolism and the mechanisms by which VMH neurons sense nutrients and hormones remain obscure. O-linked β-D-N-acetylglucosamine modification (O-GlcNAcylation), catalyzed by O-GlcNAc transferase (OGT), is considered a cellular sensor of stress, nutrients, and hormones, regulating a variety of cellular activities. Here we report that mice with VMH neuron-specific OGT deletion exhibit rapid development of obesity, increased adiposity, and reduced energy expenditure. The obesity phenotype is associated with adipocyte hypertrophy and reduced lipolytic activity of white adipose tissues, resulting from impaired sympathetic innervations of white adipose tissues. Genetic ablation of OGT in VMH neurons alters glucose sensory properties and inhibits neuronal excitability, leading to reduced sympathetic nervous activity. Collectively, this study reveals that the VMH regulates lipid metabolism through the brain-white adipose tissues axis. It also demonstrates that OGT in the VMH plays an antiobesogenic role that controls the body weight set point and energy balance.
Recommended Citation
Wang, Qi, "The Role of O-GlcNAc Transferase in Ventromedial Hypothalamic Control of Energy Balance" (2023). Yale Graduate School of Arts and Sciences Dissertations. 914.
https://elischolar.library.yale.edu/gsas_dissertations/914
