Primary Differences in Lipolysis between Human Omental and Subcutaneous Adipose Tissue Observed Using In Vitro Differentiated Adipocytes

Abstract

Catecholamine-induced lipolysis is elevated in omental as compared to subcutaneous adipocytes due to primary differences between the two cell types (i.e., they have different progenitor cells). Whether there is regional variation in atrial natriuretic peptide (ANP)-induced lipolysis is unknown. We studied whether β-adrenoceptor signaling to lipolysis and ANP-induced lipolysis are involved in the primary differences in lipolysis. In vitro experiments on differentiated preadipocytes from human subcutaneous and omental adipose tissue were performed. The cells were kept in culture for a relative long duration, so any influence of local environment and circulation in the various adipose tissue depots could be excluded. Using β1-, β2-, and β3-adenoceptor agonists, lipolysis was found to be significantly higher in omental as compared to subcutaneous differentiated preadipocytes. Forskolin and dibutyryl cAMP, which act at post-adrenoceptor levels, did not show any regional difference. There was no regional difference in ANP-induced lipolysis. Gene expression of β1- and β3-adrenoceptors was higher and β2-adrenoceptor expression was lower in the omental cells. Omental fat cells have an increased β-adrenoceptor-mediated lipolysis principally due to primary differences in the early event that couples β-adrenoceptor subtypes to G-proteins. ANP-induced lipolysis is not subject to primary regional variation.

Key words

visceral - adipocytes - lipolysis - atrial natriuretic peptide - β-adrenoceptors

References

• 1 Lafontan M, Berlan M. Fat cell adrenergic receptors and the control of white and brown fat cell function.  J Lipid Res. 1993;  34 1057-1091
• 2 Langin D. Adipose tissue lipolysis as a metabolic pathway to define pharmacological strategies against obesity and the metabolic syndrome.  Pharmacol Res. 2006;  53 482-491
• 3 Arner P. Human fat cell lipolysis: biochemistry, regulation and clinical role.  Best Pract Res Clin Endocrinol Metab. 2005;  19 471-482
• 4 Lafontan M, Moro C, Berlan M, Crampes F, Sengenes C, Galitzky J. Control of lipolysis by natriuretic peptides and cyclic GMP.  Trends Endocrinol Metab. 2008;  19 130-137
• 5 Frayn KN, Tan GD, Karpe F. Adipose tissue: a key target for diabetes pathophysiology and treatment?.  Horm Metab Res. 2007;  39 739-742
• 6 van Harmelen V, Dicker A, Ryden M, Hauner H, Lonnqvist F, Naslund E, Arner P. Increased lipolysis and decreased leptin production by human omental as compared with subcutaneous preadipocytes.  Diabetes. 2002;  51 2029-2036
• 7 Dicker A, Astrom G, Sjolin E, Hauner H, Arner P, Harmelen V van. The influence of preadipocyte differentiation capacity on lipolysis in human mature adipocytes.  Horm Metab Res. 2007;  39 282-287
• 8 van Harmelen V, Skurk T, Hauner H. Primary culture and differentiation of human adipocyte precursor cells.  Methods Mol Med. 2005;  107 125-135
• 9 Sarsero D, Molenaar P, Kaumann AJ. Validity of (-)-[3^H]-CGP 12177A as a radioligand for the ‘putative beta4-adrenoceptor’ in rat atrium.  Br J Pharmacol. 1998;  123 371-380
• 10 Hellmer J, Arner P, Lundin A. Automatic luminometric kinetic assay of glycerol for lipolysis studies.  Anal Biochem. 1989;  177 132-137
• 11 Litosch I, Hudson TH, Mills I, Li SY, Fain JN. Forskolin as an activator of cyclic AMP accumulation and lipolysis in rat adipocytes.  Mol Pharmacol. 1982;  22 109-115
• 12 Moskowitz J, Fain JN. Hormonal regulation of lipolysis and phosphorylase activity in human fat cells.  J Clin Invest. 1969;  48 1802-1808
• 13 Lafontan M, Barbe P, Galitzky J, Tavernier G, Langin D, Carpene C, Bousquet-Melou A, Berlan M. Adrenergic regulation of adipocyte metabolism.  Hum Reprod. 1997;  12 ((Suppl 1)) 6-20
• 14 Adams M, Montague CT, Prins JB, Holder JC, Smith SA, Sanders L, Digby JE, Sewter CP, Lazar MA, Chatterjee VK, O’Rahilly S. Activators of peroxisome proliferator-activated receptor gamma have depot-specific effects on human preadipocyte differentiation.  J Clin Invest. 1997;  100 3149-3153
• 15 van Harmelen V, Lonnqvist F, Thorne A, Wennlund A, Large V, Reynisdottir S, Arner P. Noradrenaline-induced lipolysis in isolated mesenteric, omental and subcutaneous adipocytes from obese subjects.  Int J Obes Relat Metab Disord. 1997;  21 972-979

Correspondence