Pioglitazone attenuates hepatic inflammation and fibrosis in phosphatidylethanolamine N-methyltransferase-deficient mice

American Journal of Physiology. Gastrointestinal and Liver Physiology
Jelske N van der VeenRené L Jacobs

Abstract

Phosphatidylethanolamine N-methyltransferase (PEMT) is an important enzyme in hepatic phosphatidylcholine (PC) biosynthesis. Pemt(-/-) mice are protected against high-fat diet (HFD)-induced obesity and insulin resistance; however, these mice develop nonalcoholic fatty liver disease (NAFLD). We hypothesized that peroxisomal proliferator-activated receptor-γ (PPARγ) activation by pioglitazone might stimulate adipocyte proliferation, thereby directing lipids from the liver toward white adipose tissue. Pioglitazone might also act directly on PPARγ in the liver to improve NAFLD. Pemt(+/+) and Pemt(-/-) mice were fed a HFD with or without pioglitazone (20 mg·kg(-1)·day(-1)) for 10 wk. Pemt(-/-) mice were protected from HFD-induced obesity but developed NAFLD. Treatment with pioglitazone caused an increase in body weight gain in Pemt(-/-) mice that was mainly due to increased adiposity. Moreover, pioglitazone improved NAFLD in Pemt(-/-) mice, as indicated by a 35% reduction in liver weight and a 57% decrease in plasma alanine transaminase levels. Livers from HFD-fed Pemt(-/-) mice were steatotic, inflamed, and fibrotic. Hepatic steatosis was still evident in pioglitazone-treated Pemt(-/-) mice; however, treatment with pioglitazone red...Continue Reading

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Citations

Apr 16, 2017·Biochimica Et Biophysica Acta. Biomembranes·Jelske N van der VeenRené L Jacobs
Jul 6, 2017·Alimentary Pharmacology & Therapeutics·S A Townsend, P N Newsome
Nov 13, 2018·Transplantation·Ivan LinaresMarkus Selzner
Jan 8, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jelske N van der VeenRené L Jacobs
Oct 13, 2017·European Journal of Gastroenterology & Hepatology·Malek YaghoubiMaryam Jameshoorani
Jul 10, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sereana WanRené L Jacobs
Jul 22, 2020·Molecular Nutrition & Food Research·Maria WallertStefan Lorkowski
May 24, 2018·Cellular and Molecular Life Sciences : CMLS·Amanda Karolina Soares Silva, Christina Alves Peixoto
Oct 16, 2020·Journal of Cellular and Molecular Medicine·Xiaojuan ZhaoLingdong Kong
Sep 12, 2021·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·Manqiu MoNing Xia

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