Protease inhibitors may reduce subcutaneous fat levels partly through down-regulation of oestrogen receptors in fat tissue, according to a report by Italian researchers published in the March 25th edition of AIDS.
Some studies have shown women to be at higher risk of fat loss than men, and the group from the universities of Padova and Verona in Italy set out to determine whether this difference might be explained through effects of antiretrovirals on oestrogen receptor levels in adipose tissue.
Sex steroid hormones such as oestrogen play a role in the differentiation of adipose cells and the consequent sex-related distribution of fat throughout the body, giving rise to the pear-shaped fat distribution seen in women and the apple-shaped fat distribution seen in men as they age. If fewer receptors for steroid hormones are present in fat, the normal distribution of fat might be altered.
In this study, the researchers recruited 14 male HIV-positive patients, six treatment-niave patients just beginning HAART and eight switching from a protease inhibitor-containing regimen to a PI-sparing regimen. Five of the switch group had lipodystrophy.
Metabolic, endocrinological and body fat measurements were evaluated at the time of treatment initiation or switch, and again six months later. Adipose tissue gene expression was also evaluated by needle biopsy of abdominal subcutaneous fat at the same time points.
Metabolic and body fat evaluation showed that patients with lipodystrophy had significantly lower subcutaneous fat levels and total body mass, but higher waist-to-hip ratio and visceral adipose fat content as measured by DEXA scan. Lipodystrophic patients also had higher total and LDL cholesterol levels, but glucose and triglyceride levels did not differ between lipodystrophic and non-lipodystrophic patients. Body fat parameters did not change after six months of HAART or after a switch of regimen.
Endocrinological analysis showed no significant difference in levels of testosterone, free testosterone, estradiol, progesterone, DHEAS, luteinising hormone (LH), follicle-stimulating hormone (FSH), adrenocorticotrophic hormone (ACTH) or urinary free cortisol.
Gene expression analysis did show differences in gene expression however. Individuals with lipodystrophy had significantly lower baseline levels of ER(beta) messenger RNA (a gene that encodes steroid hormone receptors and which is more commonly expressed in subcutaneous fat), and these levels rose significantly in all switch group patients six months after switching from a PI-containing regimen, whilst falling significantly in treatment-naïve individuals after six months of HAART.
“As sex steroid hormone levels did not significantly change in our patients during HAART, the modulation of ER(beta) expression did not seem to be a consequence of abnormal hormone levels”, the researchers note.
“Our findings suggest a role for this receptor in HIV-associated lipodystrophy, opening the avenue to investigations on selective oestrogen receptor modulators for the management of this syndrome.”
Barzon L et al. Do oestrogen receptors play a role in the pathogenesis of HIV-associated lipodystrophy? AIDS 19: 531-33, 2005.