Lipolysis Index: Evaluation of a New Tool for Metabolic Assessment in Epidemiological Studies on Obesity

Abstract

Lipid mobilization through adipocyte lipolysis is central for energy metabolism and is decreased in obesity. However, the factors of importance for lipolytic activity in the general population are not known. To further examine this we performed a cross-sectional study on teenagers and adults. We constructed and evaluated a simple index of lipolytic activity (ratio of fasting p-glycerol and body fat %) in population based samples in 316 teenagers (BMI 16–51 kg/m²) and 3 039 adults (BMI 16–70 kg/m²). In the adults, multiple regression analysis showed that waist and BMI but not age, plasma insulin, plasma noradrenaline or waist-to-hip ratio contributed independently and inversely to lipolytic activity (partial r=−0.37 and −0.28, respectively, p<0.0001). Together waist and BMI explained about 45% of the variability of lipolysis. Waist was a stronger factor than BMI in stepwise regression. The same analysis in teenagers showed that only BMI contributed independently and inversely to lipolytic activity (partial r=−0.90, p<0.0001) and explained about 55% of lipolysis variation. BMI had the strongest effect on lipolysis in lean teenagers. The results were the same for men and women. At all levels of lipolytic activity plasma fatty acid levels were elevated in obese subjects (p<0.0001). We conclude that during adolescence BMI is the major factor negatively influencing lipolytic activity, in particular among lean young subjects. In adulthood central fat accumulation together with increasing BMI decreases lipolysis. In spite of low lipolytic activity circulating fatty acid levels are increased in obesity, probably due to an adipose mass effect.

Key words

obesity - waist circumference - norepinephrine - insulin - fat cell - glycerol

References

• 1 Arner P. Human fat cell lipolysis: biochemistry, regulation and clinical role.  Best Pract Res Clin Endocrinol Metab. 2005;  19 471-482
• 2 Koutsari C, Jensen MD. Thematic review series: patient-oriented research. Free fatty acid metabolism in human obesity.  J Lipid Res. 2006;  47 1643-1650
• 3 Wolfe RR, Peters EJ, Klein S, Holland OB, Rosenblatt J, Gary Jr H. Effect of short-term fasting on lipolytic responsiveness in normal and obese human subjects.  Am J Physiol. 1987;  252 E189-E196
• 4 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
• 5 Bougneres P, Stunff CL, Pecqueur C, Pinglier E, Adnot P, Ricquier D. In vivo resistance of lipolysis to epinephrine. A new feature of childhood onset obesity.  J Clin Invest. 1997;  99 2568-2573
• 6 Hagstrom-Toft E, Bolinder J, Ungerstedt U, Arner P. A circadian rhythm in lipid mobilization which is altered in IDDM.  Diabetologia. 1997;  40 1070-1078
• 7 Agustsson T, Ryden M, Hoffstedt J, van Harmelen V, Dicker A, Laurencikiene J, Isaksson B, Permert J, Arner P. Mechanism of increased lipolysis in cancer cachexia.  Cancer Res. 2007;  67 5531-5537
• 8 Linne Y, Rossner S. Interrelationships between weight development and weight retention in subsequent pregnancies: the SPAWN study.  Acta Obstet Gynecol Scand. 2003;  82 318-325
• 9 Andersson K, Eneroth P, Arner P. Changes in circulating lipid and carbohydrate metabolites following systemic nicotine treatment in healthy men.  Int J Obes Relat Metab Disord. 1993;  17 675-680
• 10 Quisth V, Enoksson S, Blaak E, Hagstrom-Toft E, Arner P, Bolinder J. Major differences in noradrenaline action on lipolysis and blood flow rates in skeletal muscle and adipose tissue in vivo.  Diabetologia. 2005;  48 946-953
• 11 Large V, Reynisdottir S, Langin D, Fredby K, Klannemark M, Holm C, Arner P. Decreased expression and function of adipocyte hormone-sensitive lipase in subcutaneous fat cells of obese subjects.  J Lipid Res. 1999;  40 2059-2066
• 12 Haslam DW, James WP. Obesity.  Lancet. 2005;  366 1197-1209
• 13 Kumagai Y. Strategies against high blood pressure in the early morning.  Clin Exp Hypertens. 2004;  26 107-118
• 14 Harris CD. Neurophysiology of sleep and wakefulness.  Respir Care Clin N Am. 2005;  11 567-586
• 15 Lafontan M, Berlan M. Do regional differences in adipocyte biology provide new pathophysiological insights?.  Trends Pharmacol Sci. 2003;  24 276-283
• 16 Frayn KN. Regulation of fatty acid delivery in vivo.  Adv Exp Med Biol. 1998;  441 171-179
• 17 Dahlman I, Arner P. Obesity and polymorphisms in genes regulating human adipose tissue.  Int J Obes (Lond). 2007;  31 1629-1641
• 18 Suljkovicova H, Marion-Latard F, Hejnova J, Majercik M, Crampes F, De Glisezinski I, Berlan M, Riviere D, Stich V. Effect of macronutrient composition of the diet on the regulation of lipolysis in adipose tissue at rest and during exercise: microdialysis study.  Metabolism. 2002;  51 1291-1297
• 19 Kosti RI, Panagiotakos DB. The epidemic of obesity in children and adolescents in the world.  Cent Eur J Public Health. 2006;  14 151-159
• 20 Lange KH. Fat metabolism in exercise – with special reference to training and growth hormone administration.  Scand J Med Sci Sports. 2004;  14 74-99
• 21 Bennard P, Imbeault P, Doucet E. Maximizing acute fat utilization: effects of exercise, food, and individual characteristics.  Can J Appl Physiol. 2005;  30 475-499
• 22 McMurray RG, Hackney AC. Interactions of metabolic hormones, adipose tissue and exercise.  Sports Med. 2005;  35 393-412
• 23 Poirier P, Despres JP. Exercise in weight management of obesity.  Cardiol Clin. 2001;  19 459-470
• 24 Bensimhon DR, Kraus WE, Donahue MP. Obesity and physical activity: a review.  Am Heart J. 2006;  151 598-603
• 25 Boden G. Free fatty acids-the link between obesity and insulin resistance.  Endocr Pract. 2001;  7 44-51

Correspondence