Caloric restriction reverses hepatic insulin resistance and steatosis in rats with low aerobic capacity.
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.
Bowman
Thomas A
TA
Center for Diabetes and Endocrine Research, Department of Physiology and Pharmacology, College of Medicine, University of Toledo, Toledo, Ohio 43614, USA.
Ramakrishnan
Sadeesh K
SK
Kaw
Meenakshi
M
Lee
Sang Jun
SJ
Patel
Payal R
PR
Golla
Varun K
VK
Bourey
Raymond E
RE
Haram
Per Magnus
PM
Koch
Lauren G
LG
Britton
Steven L
SL
Wisløff
Ulrik
U
Lee
Abraham D
AD
Najjar
Sonia M
SM
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
D007328:Insulin; D005947:Glucose