European Journal of Nutrition

, Volume 56, Issue 2, pp 569–579 | Cite as

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

  • Myunggi Baik
  • Mi Sun Lee
  • Hyeok Joong Kang
  • Seung Ju Park
  • Min Yu Piao
  • Trang Hoa Nguyen
  • Lothar Hennighausen
Original Contribution

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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.

Keywords

STAT5 muscle deletion Lipid and glucose metabolism Intramyocellular lipid accumulation Hepatic lipid accumulation 

Abbreviations

AR

Androgen receptor

FFA

Free fatty acid

GH

Growth hormone

HFD

High-fat diet

HSL

Hormone-sensitive lipase

IGF-1

Insulin-like growth factor 1

IMCL

Increased intramyocellular lipid

LDLR

Low-density lipoprotein receptor

LPL

Lipoprotein lipase

RO

Oil Red O

STAT5

Signal transducers and activators of transcription 5

STAT5 fl/fl

STAT5a/b floxed/floxed

STAT5 MKO

Muscle-specific STAT5 knockout

TG

Triglyceride

VLDL-R

Very low-density lipoprotein receptor

Notes

Acknowledgments

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

None.

Supplementary material

394_2015_1101_MOESM1_ESM.doc (538 kb)
Supplementary material 1 (DOC 538 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Myunggi Baik
    • 1
    • 2
  • Mi Sun Lee
    • 3
  • Hyeok Joong Kang
    • 1
  • Seung Ju Park
    • 1
  • Min Yu Piao
    • 1
  • Trang Hoa Nguyen
    • 4
  • Lothar Hennighausen
    • 5
  1. 1.Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, College of Agriculture and Life SciencesSeoul National UniversitySeoulRepublic of Korea
  2. 2.Institute of Green Bio Science TechnologyPyeungchang-gunRepublic of Korea
  3. 3.Bioneer CorporationDaejeonRepublic of Korea
  4. 4.Department of Molecular BiotechnologyChonnam National UniversityGwangjuRepublic of Korea
  5. 5.Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney DiseasesNational Institutes of HealthBethesdaUSA

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