Polycystic ovary syndrome : a study of adipocyte lipolysis in relation to endocrine and metabolic status

The aim of the present thesis was to obtain insight into possible regulatory effects of androgens on the regulation of lipolysis in subcutaneous as well as visceral adipose tissue in women with the polycystic ovary syndrome (PCOS).

In non-obese women with PCOS, adrenergic lipolysis was investigated in both subcutaneous abdominal and visceral adipose tissue and several, novel disturbances were found. In subcutaneous adipose tissue, there was a markedly impaired lipolysis, due to ~10-fold decreased beta2-AR sensitivity as well as 50% reduced 02-AR density and a novel mechanism in the PKA-HSL complex, together reducing the activation of hormone sensitive lipase (HSL). Combined oral contraceptives (OC) therapy did not change the impaired lipolysis. The visceral adipose tissue lipolysis was enhanced by again stoichiometric changes in the PKA complex subunits.

These abnormalities promotes accumulation of fat in abdominal subcutaneous depot and "bum off' fat in the visceral depot, thus exposing the liver to a high FFA flux, which could contribute to dyslipidemia and hepatic insulin resistance. This is supported by anthropometric data on fat cell size and computed tomography (CT) of fat depots.

In obese subjects with PCOS, weight reduction was more effective than oral contraceptives in restoring at least in part, some defects in lipolysis in subcutaneous abdominal tissue. This indicates that in obese subjects, insulin resistance seems more important, than sex steroids in regulation of lipolysis. However in lean healthy women, ovarian downregulation, showed an impairment of catecholamine lipolysis, due to Mold decreased beta1-AR sensitivity, without affecting insulin sensitivity or the lipolysis responsiveness, speaking for a complex role of sex steroids in regulation of adipose tissue lipolysis.

Further investigations are needed to clarify the relationships between the different sex steroids in the regulation of lipolysis, both in PCOS and in healthy women.

List of scientific papers

I. Ek I, Arner P, Bergqvist A, Carlstrom K, Wahrenberg H (1997). Impaired adipocyte lipolysis in nonobese women with the polycystic ovary syndrome: a possible link to insulin resistance? J Clin Endocrinol Metab. 82(4): 1147-53.
https://pubmed.ncbi.nlm.nih.gov/9100587

II. Faulds G, Ryden M, Ek I, Wahrenberg H, Arner P (2003). Mechanisms behind Lipolytic Catecholamine Resistance of Subcutaneous Fat Cells in the Polycystic Ovarian Syndrome. J Clin Endocrinol Metab. 88(5): 2269-73.
https://pubmed.ncbi.nlm.nih.gov/12727985

III. Ek I, Arner P, Rydén M, Carlstrom K, Wahrenberg H (2003). Effects of down regulation with GnRH-a on adrenergic lipolysis in healthy regularly menstruating women. [Submitted]

IV. Wahrenberg H, Ek I, Reynisdottir S, Carlstrom K, Bergqvist A, Arner P (1999). Divergent effects of weight reduction and oral anticonception treatment on adrenergic lipolysis regulation in obese women with the polycystic ovary syndrome. J Clin Endocrinol Metab. 84(6): 2182-7.
https://pubmed.ncbi.nlm.nih.gov/10372729

V. Ek I, Arner P, Ryden M, Holm C, Thorne A, Hoffstedt J, Wahrenberg H (2002). A unique defect in the regulation of visceral fat cell lipolysis in the polycystic ovary syndrome as an early link to insulin resistance. Diabetes. 51(2): 484-92.
https://pubmed.ncbi.nlm.nih.gov/11812759