Leanne Mercier
Pronouns: She/Her
Research Mentor(s): Xinna Li
Research Mentor School/College/Department: Pathology / Medicine
Program:
Authors: Xinna Li, Leanne Mercier, Alex Voorhees
Session: Session 5: 2:40 pm – 3:30 pm
Poster: 98
Abstract
Aging is associated with alterations of lipid metabolism. A previous study conducted an in-depth analysis of the proteome changes using seven slow-aging mouse models: GHRKO mice, Snell dwarf mice, four drug treatments (rapamycin, acarbose, canagliflozin, and 17a-estradiol), and caloric restriction. In that study, as common processes intensified by multiple interventions, patterns of protein changes in the liver increasingly implicated lipid metabolism, such as via acetyl-CoA carboxylases (ACACA) and fatty acid synthase (FASN). However, the molecular mechanisms underlying the link between lipid metabolism and aging remain incompletely understood. ChREBP is a key lipogenic transcription factor responsible for the induction of gene encoding enzymes involved in fatty acid and triacylglyceride synthesis. There is a growing body of evidence suggesting that ChREBP transcription factors play important roles in the regulation of glucose and lipid metabolism. In this study, we interrogated whether and how ChREBP regulates liver lipid metabolism in conjunction with aging. We hypothesized that alterations in ChREBP underline the development of lipid metabolism in slow-aging mice. In addition, decreased lipogenesis in the liver is associated with enhanced insulin sensitivity. Furthermore, expression of ChREBP and some target genes encoding enzymes of lipid synthesis and oxidation (ex: ACACA and FASN) decreased in the liver of slow-aging mice. Our findings suggest that ChREBP plays a key role in the regulation of lipid metabolism in the liver of the slow-aging mice model. Our results provide proteins and biological mechanisms related to enhancing longevity that can inform research on therapeutic approaches to promote healthy aging.
