title: Testosterone replacement ameliorates nonalcoholic fatty liver disease in castrated male rats.
abstract: Nonalcoholic fatty liver disease is common in developed countries and is associated with obesity, metabolic syndrome, and type 2 diabetes. T deficiency is a risk factor for developing these metabolic deficiencies, but its role in hepatic steatosis has not been well studied. We investigated the effects of T on the pathogenesis of hepatic steatosis in rats fed a high-fat diet (HFD). Adult male rats were randomly placed into four groups and treated for 15 weeks: intact rats on regular chow diet (RCD), intact rats on liquid HFD (I+HFD), castrated rats on HFD (C+HFD), and castrated rats with T replacement on HFD (C+HFD+T). Fat contributed 71% energy to the HFD but only 16% of energy to the RCD. Serum T level was undetectable in castrated rats, and T replacement led to 2-fold higher mean serum T levels than in intact rats. C+HFD rats gained less weight but had higher percentage body fat than C+HFD+T. Severe micro- and macrovesicular fat accumulated in hepatocytes with multiple inflammatory foci in the livers of C+HFD. I+HFD and C+HFD+T hepatocytes demonstrated only mild to moderate microvesicular steatosis. T replacement attenuated HFD-induced hepatocyte apoptosis in castrated rats. Serum glucose and insulin levels were not increased with HFD in any group. Immunoblots showed that insulin-regulated proteins were not changed in any group. This study demonstrates that T deficiency may contribute to the severity of hepatic steatosis and T may play a protective role in hepatic steatosis and nonalcoholic fatty liver disease development without insulin resistance.
authors.affiliation: Divisions of Endocrinology, Departments of Medicine (L.N., Y.J., C.W., M.D.-A., P.Y.L., S.L., C.C., K.L., Y.L., R.S.S.) and Pediatrics (J.K.Y., W.N.P.L.), and Department of Pathology (S.W.F.) Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, California 90509.
authors.forename: L
authors.initials: L
authors.lastname: Nikolaenko
authors.forename: Y
authors.initials: Y
authors.lastname: Jia
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.forename: M
authors.initials: M
authors.lastname: Diaz-Arjonilla
authors.forename: J K
authors.initials: JK
authors.lastname: Yee
authors.forename: S W
authors.initials: SW
authors.lastname: French
authors.forename: P Y
authors.initials: PY
authors.lastname: Liu
authors.forename: S
authors.initials: S
authors.lastname: Laurel
authors.forename: C
authors.initials: C
authors.lastname: Chong
authors.forename: K
authors.initials: K
authors.lastname: Lee
authors.forename: Y
authors.initials: Y
authors.lastname: Lue
authors.forename: W N P
authors.initials: WN
authors.lastname: Lee
authors.forename: R S
authors.initials: RS
authors.lastname: Swerdloff
mesh_terms: D052242:Adiponectin / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001823:Body Composition / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002369:Castration; D004435:Eating / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005234:Fatty Liver / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020249:Hormone Replacement Therapy; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000627:therapeutic use*
chemical_list: D052242:Adiponectin; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D020738:Leptin; D013739:Testosterone