Accelerated Fatty Acid Oxidation in Muscle Averts Fasting-induced Hepatic Steatosis in SJL/J Mice

The accumulation of triglycerides (TG) in the liver, designated hepatic steatosis, is characteristically associated with obesity and insulin resistance, but it can also develop after fasting. Here, we show that fasting-induced hepatic steatosis is under genetic control in inbred mice. After a 24-h f...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2009-09, Vol.284 (36), p.24644-24652
Main Authors: Guan, Hong-Ping, Goldstein, Joseph L., Brown, Michael S., Liang, Guosheng
Format: Article
Language:English
Subjects:
Animals
Fasting - metabolism
Fatty Acids, Nonesterified - metabolism
Fatty Liver - metabolism
Fatty Liver - pathology
Lipids and Lipoproteins: Metabolism, Regulation, and Signaling
Liver - metabolism
Liver - pathology
Male
Mice
Muscle, Skeletal - metabolism
Muscle, Skeletal - pathology
Oxidation-Reduction
Time Factors
Triglycerides - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The accumulation of triglycerides (TG) in the liver, designated hepatic steatosis, is characteristically associated with obesity and insulin resistance, but it can also develop after fasting. Here, we show that fasting-induced hepatic steatosis is under genetic control in inbred mice. After a 24-h fast, C57BL/6J mice and SJL/J mice both lost more than 20% of body weight and ∼60% of total body TG. In C57BL/6J mice, TG accumulated in liver, producing frank steatosis. In striking contrast, SJL/J mice failed to accumulate any hepatic TG even though they lost nearly as much adipose tissue mass as the C57BL/6J mice. Mice from five other inbred strains developed fasting-induced steatosis like the C57BL/6J mice. Measurements of the uptake of free fatty acids (FA) in vivo and in vitro demonstrated that SJL/J mice were protected from steatosis because their heart and skeletal muscle took up and oxidized twice as much FA as compared with C57BL/6J mice. As a result of this muscle diversion, serum-free FA and ketone bodies rose much less after fasting in SJL/J mice as compared with C57BL/6J mice. When livers of SJL/J and C57BL/6J mice were perfused with similar concentrations of FA, the livers took up and esterified similar amounts. We conclude that SJL/J mice express one or more variant genes that lead to enhanced FA uptake and oxidation in muscle, thereby sparing the liver from FA overload in the fasting state.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M109.034397