Premium
Deletion of T1R3 reduces atherosclerosis and liver triglyceride accumulation in ApoE −/− mice fed a high‐fat diet
Author(s) -
Shojaat Shayla,
Engman Samuel,
Hofferber Jason,
Keomanivong Faithe,
Wauson Eric M
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.lb405
Subject(s) - mtorc1 , autophagy , nutrient sensing , chemistry , endocrinology , medicine , triglyceride , biochemistry , apoptosis , microbiology and biotechnology , cholesterol , biology , signal transduction , pi3k/akt/mtor pathway
To maintain homeostasis, cells continuously evaluate and adjust to their nutrient availability and current energy state. A cell's response to the fed state requires the presence of amino acids and other nutrients, which signal to the mammalian target of rapamycin complex 1 (mTORC1) coordinating cell growth, protein translation, and autophagy. The umami taste receptor, which is a heterodimer between the G protein‐coupled receptors T1R1 and T1R3, is a direct sensor of amino acid availability and signals to mTORC1. Reducing the expression of T1R1/T1R3 in mice and pancreatic beta and cardiomyocyte cell lines diminishes the activation of mTORC1 by amino acids, thereby inducing autophagy. Previous research suggests that elevated autophagic flux reduces the development and progression of atherosclerosis by protecting cells from oxidative stress, reducing apoptosis within atherosclerotic lesions, and promoting lesion stabilization by degrading intracellular components that are harmful to the cell. Other studies suggest that increased autophagic flux decreases the progression of Non‐Alcoholic Fatty Liver Disease (NAFLD) by reducing hepatocyte lipid accumulation and liver inflammation. We hypothesized that the deletion of T1R3 in ApoE −/− mice would decrease aortic atherosclerotic plaque buildup and decrease hepatosteatosis by increasing autophagic flux. Our data suggest that T1R3 −/− ApoE −/− mice have less liver lipid accumulation and reduced atherosclerotic plaque area when compared to T1R3 +/+ ApoE −/− mice. Taken together, these data suggest that modulation of nutrient and amino acid‐sensing GPCRs like T1R1/T1R3 could be used as a potential therapeutic strategy for cardiovascular disease. Support or Funding Information American Heart Association (15SDG25090279) and Iowa Osteopathic Education and Research Funds (E.M.W.). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .