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HO‐1 Induction Attenuates Fructose Mediated Non‐alcoholic Fatty Liver in Hepatocytes and Obese Mice : Involves SIRT1
Author(s) -
Sodhi Komal,
Shapiro Joseph,
Stec David,
Bellner Lars,
Abraham Nader
Publication year - 2015
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.29.1_supplement.846.1
Subject(s) - medicine , fructose , endocrinology , heme oxygenase , oxidative stress , fatty liver , steatohepatitis , steatosis , chemistry , hepatocyte , nonalcoholic fatty liver disease , fibrosis , heme , biochemistry , disease , in vitro , enzyme
Oxidative stress underlies pathological complication in nonalcoholic fatty liver disease (NAFLD). Heme Oxygenase‐1 (HO‐1) is a potent endogenous antioxidant gene that plays a key role in decreasing oxidative stress. Sirtuin1 (SIRT1). The aim of this study is to determine whether HO‐1 acts through SIRT1 to form a functional module within hepatocytes to attenuate fructose‐mediated steatohepatitis and hepatic fibrosis. Effect of fructose, on hepatocyte lipid accumulation and fibrosis in murine hepatocytes and in mice fed a high fructose diet in the presence and absence of CoPP, an inducer of HO‐1. Fructose increased heme and decreased HO‐1, SIRT1 and pAMPK levels in hepatocytes (p<0.05). Fructose supplementation increased the expression of FAS levels; this increase was negated by CoPP. Concurrent treatment with CoPP and SIRT1 siRNA increased FAS expression suggesting that HO‐1 is upstream of SIRT1 and suppression of SIRT1 attenuates the beneficial effects of HO‐1. A high fructose diet increased insulin resistance and fibrotic markers in mice (p<0.05). Induction of HO‐1 increased SIRT1 levels ameliorated fructose‐mediated lipid accumulation and fibrosis in liver (p<0.05 vs. fructose). Taken together, our study demonstrates, that HO‐1 induction attenuates fructose‐induced hepatic lipid deposition, prevents the development of hepatic fibrosis and abates NAFLD‐associated vascular dysfunction. Support NIH Grants HL‐55601, HL34300 (N.G.A.)