Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Paper
  • Published:

Accelerated intramyocellular triglyceride synthesis in skeletal muscle of high-fat-induced obese rats

Abstract

OBJECTIVE: To test the hypothesis that the synthesis of intramyocellular triglycerides (imcTG) in skeletal muscle is increased in obese rats in which the content of imcTG is known to be abnormally high.

ANIMALS: Sprague–Dawley male lean and high-fat-induced obese rats were studied at the age of 4, 8 and 12 months after an overnight fast, awake.

MEASUREMENTS: [U-14C]glycerol was continuously infused intravenously for 2 h followed by muscle biopsies, and intracellular glycerol incorporation into imcTG was determined. imcTG content, intramyocellular free glycerol concentration and specific activity, systemic glycerol flux and plasma glycerol, free fatty acid (FFA) and glucose concentrations were also determined.

RESULTS: The rates of incorporation of intramyocellular glycerol into imcTG (nmol/g wet muscle/h) were markedly accelerated in obese rats compared to their lean littermates at all ages: 66±12 vs 12±2 (P=0.02) for gastrocnemius and 74±29 vs 31±7 (P=0.09) for soleus when 4 months old; 223±29 vs 58±27 (P=0.001) for gastrocnemius, 224±28 vs 70±21 (P=0.001) for soleus and 294±78 vs 49±22 (P=0.02) for tibialis anterior when 8 months old; and 25±4 vs 11±2 (P=0.01) for gastrocnemius and 22±8 vs 8.4±3 (P=0.04) for soleus when 12 months old. As expected, this was accompanied by a higher imcTG content in virtually all muscles at all ages tested.

CONCLUSION: The synthesis of imcTG in skeletal muscle is grossly increased in obese rats, which likely contributes to abnormal imcTG accumulation.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Jacob S, Machann J, Rett K, Brechtel K, Volk A, Renn W, Maerker E, Matthaei S, Schick F, Claussen CD, Haring HU . Association of increased intramyocellular lipid content with insulin resistance in lean nondiabetic offsprings of type 2 diabetic subjects. Diabetes 1999; 48: 1113–1119.

    Article  CAS  Google Scholar 

  2. Koyama K, Chen G, Lee Y, Unger RH . Tissue triglycerides, insulin resistance, and insulin production: implications for hyperinsulinemia of obesity. Am J Physiol 1997; 273: E708–E713.

    CAS  PubMed  Google Scholar 

  3. Pan DA, Lillioja S, Kriketos AD, Milner MR, Baur LA, Bogardus C, Jenkins AB, Storlien LH . Skeletal muscle triglyceride levels are inversely related to insulin action. Diabetes 1997; 46: 983–988.

    Article  CAS  Google Scholar 

  4. Sinha R, Dufour S, Petersen KF, LeBon V, Enoksson S, Ma YZ, Savoye M, Rothman DL, Shulman GI, Caprio S . Assessment of skeletal muscle triglyceride content by (1)H nuclear magnetic resonance spectroscopy in lean and obese adolescents: relationships to insulin sensitivity, total body fat, and central adiposity. Diabetes 2002; 51: 1022–1027.

    Article  CAS  Google Scholar 

  5. Kraegen EW, Clark PW, Jenkins AB, Daley EA, Chisholm DJ, Storlien LH . Development of muscle insulin resistance after liver insulin resistance in high-fat-fed rats. Diabetes 1991; 40: 1397–1403.

    Article  CAS  Google Scholar 

  6. Guo ZK, Burguera B, Jensen MD . Kinetics of intramuscular triglyceride fatty acids in exercising humans. J Appl Physiol 2000; 89: 2057–2064.

    Article  CAS  Google Scholar 

  7. Guo ZK, Jensen MD . Intramuscular fatty acid metabolism evaluated with stable isotopic tracers. J Appl Physiol 1998; 84: 1674–1679.

    Article  CAS  Google Scholar 

  8. Guo ZK, Jensen MD . Blood glycerol is an important precursor for intramuscular triacylglycerol synthesis. J Biol Chem 1999; 274: 23702–23706.

    Article  CAS  Google Scholar 

  9. Dagenais GR, Tancredi RG, Zierler KL . Free fatty acid oxidation by forearm muscle at rest, and evidence for an intramuscular lipid pool in the human forearm. J Clin Invest 1976; 58: 421–431.

    Article  CAS  Google Scholar 

  10. Dyck DJ, Peters SJ, Glatz J, Gorski J, Keizer H, Kiens B, Liu S, Richter EA, Spriet LL, van der Vusse GJ, Bonen A . Functional differences in lipid metabolism in resting skeletal muscle of various fiber types. Am J Physiol 1997; 272: E340–E351.

    CAS  PubMed  Google Scholar 

  11. Eaton P, Teinberg D . Effects of medium fatty acid concentration, epinephrine, and glucose on palmitate-1-14C oxidation and incorporation into neutral lipids by skeletal muscle in vitro. J Lipid Res 1961; 2: 376–382.

    CAS  Google Scholar 

  12. Folch J, Lees M, Sloane-Standley GH . A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 1957; 226: 497–509.

    CAS  Google Scholar 

  13. Christie WW . Rapid separation and quantification of lipid classes by high performance liquid chromatography and mass (light-scattering) detection. J Lipid Res 1985; 26: 507–512.

    CAS  PubMed  Google Scholar 

  14. Humphrey SM, Fisher RM, Frayn KN . Micro-method for measurement of subnanomole amounts of triacylglycerol. Ann Clin Biochem 2000; 27: 597–598.

    Article  Google Scholar 

  15. Zierler KL . Fatty acids as substrates for heart and skeletal muscle. Circ Res 1976; 38: 459–463.

    Article  CAS  Google Scholar 

  16. Hurley BF, Nemeth PM, Martin WH III, Hagberg JM, Dalsky GP, Holloszy JO . Muscle triglyceride utilization during exercise: effect of training. J Appl Physiol 1986; 60: 562–567.

    Article  CAS  Google Scholar 

  17. Rico-Sanz J, Moosavi M, Thomas EL, McCarthy J, Coutts GA, Saeed N, Bell JD . In vivo evaluation of the effects of continuous exercise on skeletal muscle triglycerides in trained humans. Lipids 2000; 35: 1313–1318.

    Article  CAS  Google Scholar 

  18. Kiens B, Essen-Gustavsson B, Christensen NJ, Saltin B . Skeletal muscle substrate utilization during submaximal exercise in man: effect of endurance training. J Physiol (Lond) 1993; 469: 459–478.

    Article  CAS  Google Scholar 

  19. Goodpaster BH, He J, Watkins S, Kelley DE . Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes. J Clin Endocrinol Metab 2001; 86: 5755–5761.

    Article  CAS  Google Scholar 

  20. Kelley DE, Goodpaster B, Wing RR, Simoneau JA . Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity, and weight loss. Am J Physiol 1999; 277: E1130–E1141.

    Article  CAS  Google Scholar 

  21. Hegarty BD, Cooney GJ, Kraegen EW, Furler SM . Increased efficiency of fatty acid uptake contributes to lipid accumulation in skeletal muscle of high fat-fed insulin-resistant rats. Diabetes 2002; 51: 1477–1484.

    Article  CAS  Google Scholar 

  22. Turcotte LP, Swenberger JR, Zavitz TM, Yee AJ . Increased fatty acid uptake and altered fatty acid metabolism in insulin-resistant muscle of obese Zucker rats. Diabetes 2001; 50: 1389–1396.

    Article  CAS  Google Scholar 

  23. Vaughan L, Zurlo F, Ravussin E . Aging and energy expenditure. Am J Clin Nutr 1991; 53: 821–825.

    Article  CAS  Google Scholar 

  24. Guo ZK . Triglyceride content in skeletal muscle: variability and the source. Anal Biochem 2001; 296: 1–8.

    Article  CAS  Google Scholar 

  25. Guo ZK . Sampling the intramyocellular triglycerides from skeletal muscle. J Lipid Res 2001; 42: 1041–1048.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The studies were supported by NIH grant DK 60013 and a Pilot & Feasibility Project Program award from the Minnesota Obesity Center (DK 50456) to ZKG, and NIH Grants DK40484 and DK50456 from the US Public Health Service and from the Mayo Foundation to MDJ.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Z K Guo.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Guo, Z., Jensen, M. Accelerated intramyocellular triglyceride synthesis in skeletal muscle of high-fat-induced obese rats. Int J Obes 27, 1014–1019 (2003). https://doi.org/10.1038/sj.ijo.0802380

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0802380

Keywords

This article is cited by

Search

Quick links