Muscle-specific deletion of signal transducer and activator of transcription 5 augments lipid accumulation in skeletal muscle and liver of mice in response to high-fat diet
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Growth hormone (GH) controls liver metabolism through the transcription factor signal transducer and activator of transcription 5 (STAT5). However, it remains to be fully understood to what extent other GH/STAT5 target tissues contribute to lipid and glucose metabolism. This question was now addressed in muscle-specific STAT5 knockout (STAT5 MKO) mice model.
Changes in lipid and glucose metabolism were investigated at physiological and molecular levels in muscle and liver tissues of STAT5 MKO mice under normal diet or high-fat diet (HFD) conditions.
STAT5 MKO mice exhibited an increased intramyocellular lipid (IMCL) accumulation in the quadriceps in HFD group. Decreased lipolytic hormone-sensitive lipase transcript levels may contribute to the increased IMCL accumulation in STAT5 MKO mice. STAT5 MKO induced hepatic lipid accumulation without deregulated STAT5 signaling. The upregulation of lipoprotein lipase and Cd36 mRNA levels, an increased trend of very low-density lipoprotein receptor mRNA levels, and elevated circulating concentrations of free fatty acid, triglyceride, and total cholesterol support the increase in hepatic lipid accumulation.
STAT5 MKO in conjunction with a HFD deregulated both lipid and glucose metabolism in skeletal muscle, and this deregulation induced hepatic fat accumulation via increased circulating glucose, FFA, and TG concentrations. Our study emphasizes that muscle-specific STAT5 signaling is important for balancing lipid and glucose metabolism in peripheral tissues, including muscle and liver and that the deregulation of local STAT5 signaling augments HFD-induced lipid accumulation in both muscle and liver.
KeywordsSTAT5 muscle deletion Lipid and glucose metabolism Intramyocellular lipid accumulation Hepatic lipid accumulation
Free fatty acid
Insulin-like growth factor 1
Increased intramyocellular lipid
Low-density lipoprotein receptor
Oil Red O
Signal transducers and activators of transcription 5
- STAT5 fl/fl
- STAT5 MKO
Muscle-specific STAT5 knockout
Very low-density lipoprotein receptor
The present study was supported by grants from the National Research Laboratory Program (ROA-2007-0056702) through the NRF funded by the Ministry of Education, Science, and Technology and the Next-Generation BioGreen 21 Program (No. PJ01114001), Rural Development Administration, Republic of Korea.
Compliance with ethical standards
Conflict of interest
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