Fatty Acids Inhibit Intramyocellular Triglyceride Synthesis and Turnover Acutely in High Fat-fed Obese Rats

Abstract

Obesity is associated with hyperlipidemia and enlarged intramyocellular triglyceride (imcTG) stores. The latter is strongly correlated with muscle insulin resistance. However, whether hyperlipidemia plays a role in imcTG accumulation is unknown. In the present study, the effects of plasma fatty acids on imcTG fractional turnover rate (FTR) and synthesis in skeletal muscle of high fat-fed obese rats have been examined using pulse-chase technique. imcTG was prelabeled (pulse) by continuous infusion of U-¹⁴Cglycerol and then the loss of ¹⁴C-labels from imcTG was chased while exogenous fatty acids were infused at 0 (saline), 1 (L) or 3 (H) μmol/kg/min. imcTG synthesis was determined using 2-³Hglycerol during the chase. L and H fatty acid infusions raised plasma fatty acids by 14% (p=0.02) and 30% (p=0.001), respectively, while plasma insulin and glycerol and the rate of glycerol appearance remained unchanged (p>0.05). imcTG FTR was suppressed by 36-40% and 48% in gastrocnemius and tibialis anterior, respectively (both p<0.05), and imcTG synthesis was suppressed by 50-60% in the same muscles (both p<0.05). In contrast, neither turnover nor synthesis of imcTG in soleus was affected by fatty acid infusion (p>0.05). imcTG content and the activities of diglyceride acyltransferase and hormone sensitive lipase were not affected by fatty acid infusion. The findings suggested that elevated plasma fatty acids suppress imcTG turnover and synthesis simultaneously and thus do not appear to promote imcTG accumulation in this obesity model at least in short term.

Key words

Skeletal muscle - free fatty acids - triglycerides - turnover - synthesis - obesity

References

• 1 Storlien LH, Jenkins AB, Chrisholm DJ, Pascoe WS, Khouri S, Kraegen EW. Diabetes. 1991;  40 280-289
• 2 Pan DA, Lillioja S, Kriketos AD, Milner MR, Baur LA, Bogardus C, Jenkins AB, Storlien LH. Diabetes. 1997;  46 983-988
• 3 Shulman GI. J Clin Invest. 2000;  106 171-176
• 4 Kelley DE, Goodpaster BH. Diabetes Care. 2001;  24 933-941
• 5 Felber JP, Ferrannini E, Golay A, Meyer HU, Theibaud D, Curchod B, Maeder E, Jequier E, DeFronzo RA. Diabetes. 1987;  36 1341-1350
• 6 Yee AJ, Turcotte LP. Am J Physiol Endocrinol Metab. 2002;  283 E73-E77
• 7 Gorska M, Rutkiewicz J, Gorski J. Acta Physiol Pol. 1990;  41 171-176
• 8 de Groot MJ, Willemsen PH, Coumans WA, van Bilsen M, van der Vusse GJ. Biochim Biophys Acta. 1989;  1006 111-115
• 9 Armstrong RB, Phelps RO. Am J Anat. 1984;  171 259-272
• 10 Guo Z, Zhou L. Lab Anim (NY). 2003;  32 45-48
• 11 Folch J, Lees M, Sloane-Standley GH. J Biol Chem. 1957;  226 497-509
• 12 Humphreys SM, Fisher RM, Frayn KN. Ann Clin Biochem. 1990;  27 597-598
• 13 Langfort J, Ploug T, Ihlemann J, Saldo M, Holm C, Galbo H. Biochem J. 1999;  340 ((Pt 2)) 459-465
• 14 Lozeman FJ, Middleton CK, Deng J, Kazala EC, Verhaege C, Mir PS, Laroche A, Bailey DR, Weselake RJ. Comp Biochem Physiol B Biochem Mol Biol. 2001;  130 105-115
• 15 Guo Z, Burguera B, Jensen MD. J Appl Physiol. 2000;  89 2057-2064
• 16 Guo ZK, Jensen MD. J Biol Chem. 1999;  274 23702-23706
• 17 Groop LC, Bonadonna RC, Shank M, Petrides AS, DeFronzo RA. J Clin Invest. 1991;  87 83-89
• 18 Hagstrom-Toft E, Thorne A, Reynisdottir S, Moberg E, Rossner S, Bolinder J, Arner P. Diabetes. 2001;  50 1604-1611
• 19 Horowitz JF, Mora-Rodriguez R, Byerley LO, Coyle EF. Am J Physiol. 1997;  273 E768-E775
• 20 Hopp JF, Palmer WK. Metabolism. 1991;  40 223-225
• 21 Denton RM, Yorke RE, Randle PJ. Biochem J. 1966;  100 407-419
• 22 Guo ZK. J Appl Physiol. 2004;  96 1569-1570
• 23 Neumann-Haefelin C, Beha A, Kuhlmann J, Belz U, Gerl M, Quint M, Biemer-Daub G, Broenstrup M, Stein M, Kleinschmidt E, Schaefer HL, Schmoll D, Kramer W, Juretschke HP, Herling AW. Diabetes. 2004;  53 528-534
• 24 Poynten AM, Gan SK, Kriketos AD, O'Sullivan A, Kelly JJ, Ellis BA, Chisholm DJ, Campbell LV. Metabolism. 2003;  52 699-704
• 25 Turcotte LP, Kiens B, Richter EA. FEBS Lett. 1991;  279 327-329
• 26 Bonen A, Benton CR, Campbell SE, Chabowski A, Clarke DC, Han XX, Glatz JF, Luiken JJ. Acta Physiol Scand. 2003;  178 347-356
• 27 Nawrocki A, Gorski J. Horm Metab Res. 2004;  36 601-606
• 28 Guo ZK. Horm Metab Res. 2005;  37 776-778

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