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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
Author(s) -
Conti Aline,
Tryndyak Volodymyr,
Willett Rose A.,
BorowaMazgaj Barbara,
Watson Anna,
Patton Ralph,
Khare Sangeeta,
Muskhelishvili Levan,
Olson Greg R.,
Avigan Mark I.,
Cerniglia Carl E.,
Ross Sharon A.,
Sanyal Arun J.,
Beland Frederick A.,
Rusyn Ivan,
Pogribny Igor P.
Publication year - 2020
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/fj.202000194r
Subject(s) - nonalcoholic fatty liver disease , cd36 , medicine , endocrinology , steatosis , lipogenesis , biology , fatty liver , population , insulin resistance , obesity , disease , lipid metabolism , receptor , environmental health
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.