Premium
Retracted: Increased HO‐1 levels ameliorate fatty liver development through a reduction of heme and recruitment of FGF21
Author(s) -
Hinds Terry D.,
Sodhi Komal,
Meadows Charles,
Fedorova Larisa,
Puri Nitin,
Kim Dong Hyun,
Peterson Stephen J.,
Shapiro Joseph,
Abraham Nader G.,
Kappas Attallah
Publication year - 2014
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.20559
Subject(s) - medicine , endocrinology , heme oxygenase , lipogenesis , fatty liver , chemistry , fatty acid synthase , glycogen , fgf21 , leptin , heme , steatosis , copp , lipid metabolism , obesity , biochemistry , receptor , enzyme , disease , fibroblast growth factor
Objective Obese leptin deficient (ob/ob) mice are a model of adiposity that displays increased levels of fat, glucose, and liver lipids. Our hypothesis is that HO‐1 overexpression ameliorates fatty liver development. Methods Obese mice were administered cobalt protoporphyrin (CoPP) and stannic mesoporphyrin (SnMP) for 6 weeks. Heme, HO‐1, HO activity, PGC1α, FGF21, glycogen content, and lipogenesis were assessed. Results CoPP administration increased hepatic HO‐1 protein levels and HO activity, decreased hepatic heme, body weight gain, glucose levels, and resulted in decreased steatosis. Increased levels of HO‐1 produced a decrease in lipid droplet size, Fatty acid synthase (FAS) levels involving recruitment of FGF21, PPARα, and Glut 1. These beneficial effects were reversed by inhibition of HO activity. Conclusion Increased levels of HO‐1 and HO activity reduced the levels of obesity by reducing hepatic heme and lipid accumulation. These changes were manifested by decreases in cellular heme, increases in FGF21, glycogen content, and fatty liver. The beneficial effect of HO‐1 induction results from an increase in PPARα and FGF21 levels and a decrease in PGC1α, levels they were reversed by SnMP. Low levels of HO‐1 and HO activity are responsible for fatty liver.