title: Caloric restriction reverses hepatic insulin resistance and steatosis in rats with low aerobic capacity.
abstract: Rats selectively bred for low aerobic running capacity exhibit the metabolic syndrome, including hyperinsulinemia, insulin resistance, visceral obesity, and dyslipidemia. They also exhibit features of nonalcoholic steatohepatitis, including chicken-wire fibrosis, inflammation, and oxidative stress. Hyperinsulinemia in these rats is associated with impaired hepatic insulin clearance. The current studies aimed to determine whether these metabolic abnormalities could be reversed by caloric restriction (CR). CR by 30% over a period of 2-3 months improved insulin clearance in parallel to inducing the protein content and activation of the carcinoembryonic antigen-related cell adhesion molecule 1, a main player in hepatic insulin extraction. It also reduced glucose and insulin intolerance and serum and tissue (liver and muscle) triglyceride levels. Additionally, CR reversed inflammation, oxidative stress, and fibrosis in liver. The data support a significant role of CR in the normalization of insulin and lipid metabolism in liver.
authors.affiliation: Center for Diabetes and Endocrine Research, Department of Physiology and Pharmacology, College of Medicine, University of Toledo, Toledo, Ohio 43614, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Bowman
authors.forename: Sadeesh K
authors.initials: SK
authors.lastname: Ramakrishnan
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Kaw
authors.forename: Sang Jun
authors.initials: SJ
authors.lastname: Lee
authors.forename: Payal R
authors.initials: PR
authors.lastname: Patel
authors.forename: Varun K
authors.initials: VK
authors.lastname: Golla
authors.forename: Raymond E
authors.initials: RE
authors.lastname: Bourey
authors.forename: Per Magnus
authors.initials: PM
authors.lastname: Haram
authors.forename: Lauren G
authors.initials: LG
authors.lastname: Koch
authors.forename: Steven L
authors.initials: SL
authors.lastname: Britton
authors.forename: Ulrik
authors.initials: U
authors.lastname: Wisløff
authors.forename: Abraham D
authors.initials: AD
authors.lastname: Lee
authors.forename: Sonia M
authors.initials: SM
authors.lastname: Najjar
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D031204:Caloric Restriction; D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009765:Obesity / Q000378:metabolism; D018384:Oxidative Stress; D010805:Physical Conditioning, Animal; D011897:Random Allocation; D051381:Rats
chemical_list: D007328:Insulin; D005947:Glucose