Characterization of the variability in the extent of nonalcoholic fatty liver induced by a high-fat diet in the genetically diverse Collaborative Cross mouse model.

Autor: de Conti A; Division of Biochemical Toxicology, FDA-National Center for Toxicological Research, Jefferson, AR, USA., Tryndyak V; Division of Biochemical Toxicology, FDA-National Center for Toxicological Research, Jefferson, AR, USA., Willett RA; Division of Biochemical Toxicology, FDA-National Center for Toxicological Research, Jefferson, AR, USA., Borowa-Mazgaj B; Division of Biochemical Toxicology, FDA-National Center for Toxicological Research, Jefferson, AR, USA., Watson A; Division of Biochemical Toxicology, FDA-National Center for Toxicological Research, Jefferson, AR, USA., Patton R; Toxicologic Pathology Associates, Jefferson, AR, USA., Khare S; Division of Microbiology, FDA-National Center for Toxicological Research, Jefferson, AR, USA., Muskhelishvili L; Toxicologic Pathology Associates, Jefferson, AR, USA., Olson GR; Toxicologic Pathology Associates, Jefferson, AR, USA., Avigan MI; Office of Pharmacovigilance and Epidemiology, FDA-Center for Drug Evaluation and Research, Silver Spring, MD, USA., Cerniglia CE; Division of Microbiology, FDA-National Center for Toxicological Research, Jefferson, AR, USA., Ross SA; Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, USA., Sanyal AJ; Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA., Beland FA; Division of Biochemical Toxicology, FDA-National Center for Toxicological Research, Jefferson, AR, USA., Rusyn I; Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, USA., Pogribny IP; Division of Biochemical Toxicology, FDA-National Center for Toxicological Research, Jefferson, AR, USA.
Jazyk: angličtina
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2020 Jun; Vol. 34 (6), pp. 7773-7785. Date of Electronic Publication: 2020 Apr 18.
DOI: 10.1096/fj.202000194R
Abstrakt: Interindividual variability and sexual dimorphisms in the development of nonalcoholic fatty liver disease (NAFLD) are still poorly understood. In the present study, male and female strains of Collaborative Cross (CC) mice were fed a high-fat and high-sucrose (HF/HS) diet or a control diet for 12 weeks to investigate interindividual- and sex-specific variations in the development of NAFLD. The severity of liver steatosis varied between sexes and individual strains and was accompanied by an elevation of serum markers of insulin resistance, including increases in total cholesterol, low-density lipoproteins, high-density lipoproteins, phospholipids, and glucose. The development of NAFLD was associated with overexpression of the critical fatty acid uptake and de novo lipogenesis genes Pparg, Mogat1, Cd36, Acaab1, Fabp2, and Gdf15 in male and female mice. The expression of Pparg, Mogat1, and Cd36 was positively correlated with liver triglycerides in male mice, and Mogat1 and Cd36 expression were positively correlated with liver triglycerides in female mice. Our results indicate the value of CC mice in combination with HF/HS diet-induced alterations as an approach to study the susceptibility and interindividual variabilities in the pathogenesis of nonalcoholic fatty liver and early nonalcoholic steatohepatitis at the population level, uncovering of susceptible and resistant cohorts, and identifying sex-specific molecular determinants of disease susceptibility.
(© 2020 Federation of American Societies for Experimental Biology.)
Databáze: MEDLINE
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