Diabetes, Vol 49, Issue 9 1427-1433, Copyright © 2000 by American Diabetes Association

ARTICLES

Local factors modulate tissue-specific NEFA utilization: assessment in rats using 3H-(R)-2-bromopalmitate

SM Furler, GJ Cooney, BD Hegarty, MY Lim-Fraser, EW Kraegen and ND Oakes
Diabetes & Metabolism Research Program, Garvan Institute of Medical Research, Sydney, New South Wales, Australia. s.furler@garvan.unsw.edu.au

Insulin-resistant states are associated with accumulation of muscle lipid, suggesting an imbalance between lipid uptake and oxidation. We have employed a new fatty-acid tracer [9,10-3H]-(R)-2-bromopalmitate (3H-R-BrP) to study individual-tissue nonesterified fatty acid (NEFA) uptake in states with diminished or enhanced lipid oxidation. 3H-R-BrP was administered to conscious male Wistar rats (approximately 300 g) during fasting (5, 18, or 36 h), acute blockade of beta-oxidation (etomoxir, 15 micromol/kg), and insulin infusion (0.25 U x kg(-1) x h(-1)). Estimates of NEFA clearance rates (K(f)*) and absolute rates of uptake (R(f)*) were calculated from tissue accumulation of 3H-R-BrP products. In the basal state, NEFA uptake was dependent on the oxidative capacity of tissues: R(f)* in brown adipose tissue (BAT) > heart (HRT) > diaphragm (DPHM) > red quadriceps (RQ) > white quadriceps (WQ) > white adipose tissue (WAT). Fasting increased (P < 0.001) K(f)* in WAT but did not change NEFA clearance in other tissues. However, plasma NEFA levels were raised (P < 0.01), tending to elevate R(f)* in most tissues (P < 0.05: WAT, BAT, WQ, DPHM). Etomoxir reduced (P < 0.01) K(f)* only in oxidative tissues (BAT, RQ, DPHM, HRT). Insulin lowered plasma NEFA levels (P < 0.001) and significantly decreased R(f)* in most tissues (P < 0.05: WAT, RQ, DPHM, HRT). An increased (P < 0.05) clearance was observed in WAT, BAT, and WQ; a decrease (P < 0.01) in K(f)* was observed in HRT. This study is the first to measure tissue-specific NEFA uptake in conscious rats in the postabsorptive, fasted, and insulin-stimulated states. We have demonstrated that tissue NEFA utilization is not exclusively determined by systemic availability, but that the early steps of NEFA uptake or metabolic sequestration can also be rapidly modulated by local processes such as NEFA oxidation.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. Koutsari, D. A. Dumesic, B. W. Patterson, S. B. Votruba, and M. D. Jensen Plasma Free Fatty Acid Storage in Subcutaneous and Visceral Adipose Tissue in Postabsorptive Women Diabetes, May 1, 2008; 57(5): 1186 - 1194. [Abstract] [Full Text] [PDF]

				H. A. Parkes, E. Preston, D. Wilks, M. Ballesteros, L. Carpenter, L. Wood, E. W. Kraegen, S. M. Furler, and G. J. Cooney Overexpression of acyl-CoA synthetase-1 increases lipid deposition in hepatic (HepG2) cells and rodent liver in vivo Am J Physiol Endocrinol Metab, October 1, 2006; 291(4): E737 - E744. [Abstract] [Full Text] [PDF]

				K. Fosgerau, C. Fledelius, K. E Pedersen, J. B Kristensen, J. R Daugaard, M. A Iglesias, E. W Kraegen, and S. M Furler Oral administration of glucose promotes intracellular partitioning of fatty acid toward storage in white but not in red muscle. J. Endocrinol., September 1, 2006; 190(3): 651 - 658. [Abstract] [Full Text] [PDF]

				N. D. Oakes, P. Thalen, E. Aasum, A. Edgley, T. Larsen, S. M. Furler, B. Ljung, and D. Severson Cardiac metabolism in mice: tracer method developments and in vivo application revealing profound metabolic inflexibility in diabetes Am J Physiol Endocrinol Metab, May 1, 2006; 290(5): E870 - E881. [Abstract] [Full Text] [PDF]

				M. A. Iglesias, S. M. Furler, G. J. Cooney, E. W. Kraegen, and J.-M. Ye AMP-Activated Protein Kinase Activation by AICAR Increases Both Muscle Fatty Acid and Glucose Uptake in White Muscle of Insulin-Resistant Rats In Vivo Diabetes, July 1, 2004; 53(7): 1649 - 1654. [Abstract] [Full Text] [PDF]

				B. D. Hegarty, S. M. Furler, N. D. Oakes, E. W. Kraegen, and G. J. Cooney Peroxisome Proliferator-Activated Receptor (PPAR) Activation Induces Tissue-Specific Effects on Fatty Acid Uptake and Metabolism in Vivo--A Study Using the Novel PPAR{alpha}/{gamma} Agonist Tesaglitazar Endocrinology, July 1, 2004; 145(7): 3158 - 3164. [Abstract] [Full Text] [PDF]

				A. Seppala-Lindroos, S. Vehkavaara, A.-M. Hakkinen, T. Goto, J. Westerbacka, A. Sovijarvi, J. Halavaara, and H. Yki-Jarvinen Fat Accumulation in the Liver Is Associated with Defects in Insulin Suppression of Glucose Production and Serum Free Fatty Acids Independent of Obesity in Normal Men J. Clin. Endocrinol. Metab., July 1, 2002; 87(7): 3023 - 3028. [Abstract] [Full Text] [PDF]

				J. N. Rottman, D. Bracy, C. Malabanan, Z. Yue, J. Clanton, and D. H. Wasserman Contrasting effects of exercise and NOS inhibition on tissue-specific fatty acid and glucose uptake in mice Am J Physiol Endocrinol Metab, July 1, 2002; 283(1): E116 - E123. [Abstract] [Full Text] [PDF]

				A. Hevener, D. Reichart, A. Janez, and J. Olefsky Female Rats Do Not Exhibit Free Fatty Acid-Induced Insulin Resistance Diabetes, June 1, 2002; 51(6): 1907 - 1912. [Abstract] [Full Text] [PDF]

				B. D. Hegarty, G. J. Cooney, E. W. Kraegen, and S. M. Furler Increased Efficiency of Fatty Acid Uptake Contributes to Lipid Accumulation in Skeletal Muscle of High Fat-Fed Insulin-Resistant Rats Diabetes, May 1, 2002; 51(5): 1477 - 1484. [Abstract] [Full Text] [PDF]

				A. L. Hevener, D. Reichart, A. Janez, and J. Olefsky Thiazolidinedione Treatment Prevents Free Fatty Acid-Induced Insulin Resistance in Male Wistar Rats Diabetes, October 1, 2001; 50(10): 2316 - 2322. [Abstract] [Full Text]

				A. Virkamaki, E. Korsheninnikova, A. Seppala-Lindroos, S. Vehkavaara, T. Goto, J. Halavaara, A.-M. Hakkinen, and H. Yki-Jarvinen Intramyocellular Lipid Is Associated With Resistance to In Vivo Insulin Actions on Glucose Uptake, Antilipolysis, and Early Insulin Signaling Pathways in Human Skeletal Muscle Diabetes, October 1, 2001; 50(10): 2337 - 2343. [Abstract] [Full Text]