Terry D. Hinds, Jr. and Komal Sodhi contributed equally to this work
Increased HO-1 levels ameliorate fatty liver development through a reduction of heme and recruitment of FGF21
Article first published online: 2 DEC 2013
Copyright © 2013 The Obesity Society
How to Cite
Hinds, T. D., Sodhi, K., Meadows, C., Fedorova, L., Puri, N., Kim, D. H., Peterson, S. J., Shapiro, J., Abraham, N. G. and Kappas, A. (2013), Increased HO-1 levels ameliorate fatty liver development through a reduction of heme and recruitment of FGF21. Obesity. doi: 10.1002/oby.20559
Funding agencies: This work was supported by National Institutes of Health grants HL55601 and HL34300 (NGA) and gifts from the Renfield Foundation to The Rockefeller University (AK).
Disclosure: The authors declared no conflict of interest.
- Article first published online: 2 DEC 2013
- Accepted manuscript online: 9 JUL 2013 09:16AM EST
- Manuscript Accepted: 6 JUN 2013
- Manuscript Received: 11 DEC 2012
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.
Design and 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.
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.
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.