Adipose Tissue Metabolism - An Aspect We Should not Neglect?

Abstract

Free fatty acids (FFAs) are the most metabolically important products of adipose tissue lipolysis. Experimentally creating high FFA concentrations can reproduce the metabolic abnormalities of obesity in lean, healthy persons and lowering FFA concentrations can improve the metabolic health of upper body obese individuals. FFA concentrations are determined by both the release of FFAs into the bloodstream and the clearance of FFAs from the bloodstream. Normal FFA release rates are different in men and women and total FFA release is closely linked to resting energy expenditure. Upper body subcutaneous fat, visceral fat, and leg fat depots contribute differently to the exposure of various tissues to FFAs. The implications of regional adipose tissue lipolysis to systemic FFA availability and the effect of different approaches to treatment of obesity are discussed.

free fatty acids - lipolysis - body fat distribution - obesity

References

• 1 Aarsland A, Chinkes D, Wolfe RR. Contributions of de novo synthesis of fatty acids to total VLDL-triglyceride secretion during prolonged hyperglycemia/hyperinsulinemia in normal man.  J Clin Invest. 1996;  98 2008-2017
• 2 Uranga AP, Levine J, Jensen M. Isotope tracer measures of meal fatty acid metabolism: reproducibility and effects of the menstrual cycle.  Am J Physiol Endocrinol Metab. 2005;  288 E547-E555
• 3 Romanski SA, Nelson R, Jensen MD. Meal fatty acid uptake in adipose tissue: Gender effects in non-obese humans.  Am J Physiol Endocrinol Metab. 2000;  279 E455-E462
• 4 Jensen MD, Sarr MG, Dumesic DA, Southorn PA, Levine JA. Regional uptake of meal fatty acids in humans.  Am J Physiol Endocrinol Metab. 2003;  285 E1282-E1288
• 5 Nielsen S, Guo Z, Albu JB, Klein S, O'Brien PC, Jensen MD. Energy expenditure, sex, and endogenous fuel availability in humans.  J Clin Invest. 2003;  111 981-988
• 6 Roust LR, Jensen MD. Postprandial free fatty acid kinetics are abnormal in upper body obesity.  Diabetes. 1993;  42 1567-1573
• 7 Ahlborg G, Felig P, Hagenfeldt L, Hendler R, Wahren J. Substrate turnover during prolonged exercise in man. Splanchnic and leg metabolism of glucose, free fatty acids, and amino acids.  J Clin Invest. 1974;  53 1080-1090
• 8 Wahren J, Sato Y, Ostman J, Hagenfeldt L, Felig P. Turnover and splanchnic metabolism of free fatty acids and ketones in insulin-dependent diabetics at rest and in response to exercise.  J Clin Invest. 1984;  73 1367-1376
• 9 Kanaley JA, Cryer PE, Jensen MD. Fatty acid kinetic responses to exercise. Effects of obesity, body fat distribution, and energy-restricted diet.  J Clin Invest. 1993;  92 255-261
• 10 Kanaley JA, Mottram CD, Scanlon PD, Jensen MD. Fatty acid kinetic responses to running above or below lactate threshold.  J Appl Physiol. 1995;  79 439-447
• 11 Jensen MD, Haymond MW, Rizza RA, Cryer PE, Miles JM. Influence of body fat distribution on free fatty acid metabolism in obesity.  J Clin Invest. 1989;  83 1168-1173
• 12 Guo ZK, Hensrud DD, Johnson CM, Jensen MD. Regional postprandial fatty acid metabolism in different obesity phenotypes.  Diabetes. 1999;  48 1586-1592
• 13 Nielsen S, Guo ZK, Johnson CM, Hensrud DD, Jensen MD. Splanchnic lipolysis in human obesity.  J Clin Invest. 2004;  113 1582-1588
• 14 Martin ML, Jensen MD. Effects of body fat distribution on regional lipolysis in obesity.  J Clin Invest. 1991;  88 609-613
• 15 Jensen MD. Gender differences in regional fatty acid metabolism before and after meal ingestion.  J Clin Invest. 1995;  96 2297-2303
• 16 Basu A, Basu R, Shah P, Vella A, Rizza RA, Jensen MD. Systemic and regional free fatty acid metabolism in type 2 diabetes.  Am J Physiol Endocrinol Metab. 2001;  280 E1000-E1006
• 17 Jensen MD, Cardin S, Edgerton D, Cherrington A. Splanchnic free fatty acid kinetics.  Am J Physiol Endocrinol Metab. 2003;  284 E1140-E1148
• 18 Kelley DE, Mokan M, Simoneau JA, Mandarino LJ. Interaction between glucose and free fatty acid metabolism in human skeletal muscle.  J Clin Invest. 1993;  92 91-98
• 19 Steinberg HO, Tarshoby M, Monestel R, Hook G, Cronin J, Johnson A, Bayazeed B, Baron AD. Elevated circulating free fatty acid levels impair endothelium-dependent vasodilation.  J Clin Invest. 1997;  100 1230-1239
• 20 Bollheimer LC, Skelly RH, Chester MW, MacGarry JD, Rhodes CJ. Chronic exposure to free fatty acid reduces pancreatic β cell insulin content by increasing basal insulin secretion that is not compensated for by a corresponding increase in proinsulin biosynthesis translation.  J Clin Invest. 1998;  101 1094-1101
• 21 Ferrannini E, Barrett EJ, Bevilacqva S, DeFronzo RA. Effect of fatty acids on glucose production and utilization in man.  J Clin Invest. 1983;  72 1737-1747
• 22 Lewis GF, Uffelman KD, Szeto LW, Weller B, Steiner G. Interaction between free fatty acids and insulin in the acute control of very low density lipoprotein production in humans.  J Clin Invest. 1995;  95 158-166
• 23 Bajaj M, Suraamornkul S, Kashyap S, Cusi K, Mandarino L, DeFronzo RA. Sustained reduction in plasma free fatty acid concentration improves insulin action without altering plasma adipocytokine levels in subjects with strong family history of type 2 diabetes.  J Clin Endocrinol Metab. 2004;  89 4649-4655
• 24 Shadid S, Jensen MD. Pioglitazone increases non-esterified fatty acid clearance in upper body obesity.  Diabetologia. 2006;  49 149-157

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