[5] INCREASED EXPRESSION OF 11β-HYDROXYSTEROID DEHYDROGENASE TYPE 1 IN SUBCUTANEOUS ADIPOSE TISSUE IN HIV-ASSOCIATED LIPODYSTROPHY

5th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV

8–11 July 2003, Le Meridien Montparnasse, Paris, France

INCREASED EXPRESSION OF 11β-HYDROXYSTEROID DEHYDROGENASE TYPE 1 IN SUBCUTANEOUS ADIPOSE TISSUE IN HIV-ASSOCIATED LIPODYSTROPHY

Antiviral Therapy 2003; 8:L8 (abstract 5)

J Sutinen^1,2, K Kannisto³, E Korsheninnikova⁴, T Nyman⁴, A Hamsten³, D Wake⁵, B Walker⁵ and H Yki-Jarvinen^1,3
¹Divisions of Diabetes, Department of Medicine, University of Helsinki, Helsinki, Finland; ²Infectious Diseases, Department of Medicine, University of Helsinki, Helsinki, Finland; ³King Gustaf V Research Institute, Karolinska Institutet, Stockholm, Sweden; ⁴Minerva Research Institute, Helsinki, Finland; and ⁵Endocrinology Unit, University of Edinburgh, Edinburgh, UK

BACKGROUND/AIMS: Highly active antiretroviral therapy (HAART) has dramatically improved the prognosis of HIV-infection, but is also associated with severe adverse events, such as lipodystrophy and insulin resistance. Patients with HAART-associated lipodystrophy do not have systemic hypercortisolism, although their phenotype shares some similarities with Cushing's syndrome. 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) converts inactive cortisone to active cortisol. Mice overexpressing 11βHSD1 selectively in adipose tissue are centrally obese, hyperglycaemic and dyslipidaemic. In obese humans, 11βHSD1 activity is increased in adipose tissue. We determined whether 11βHSD1 expression is increased in adipose tissue of patients with HAART-associated lipodystrophy.

METHODS: A group of HIV-positive patients with HAART-associated lipodystrophy (LD+, n=30) was compared with a group of HIV-positive patients receiving HAART but without lipodystrophy (LD-, n=13). The mRNA levels of 11βHSD1 and β2-microglobulin (housekeeping gene) in subcutaneous adipose tissue biopsies were measured using real-time polymerase chain reaction (PCR). Liver fat (LFAT) was measured using proton spectroscopy and intra-abdominal (i.a.) and subcutaneous (s.c.) fat by magnetic resonance imaging.

RESULTS: Body mass indices (BMIs) were comparable (23.6 ±0.5 vs 22.4 ±1.1 kg/m², LD+ vs LD-, NS), but the LD+ group had significantly more intra-abdominal (1900 ±200 vs 900 ±300 cm³, P<0.01) and less subcutaneous (1100 ±200 vs 1800 ±300 cm³, P<0.05) fat than the LD- group. LFAT (8 ±2 vs 2 ±1 %, P<0.001) and fasting serum insulin concentrations (11 ±1 vs 7 ±1 mU/l, P<0.01) were significantly higher in the LD+ than the LD- group. The mRNA concentration of 11βHSD1 relative to β2-microglobulin was significantly higher in the LD+ than the LD- group (0.29 ±0.20 vs 0.09 ±0.07, P<0.001). In all HAART-treated patients, 11βHSD1 mRNA levels correlated with features of insulin resistance: fasting serum triglycerides (r=0.56, P<0.001), insulin (r=0.49, P=0.001) and high-density lipoprotein (HDL)-cholestrol (r=-0.48, P<0.01) and intra-abdominal fat (r=0.54, P<0.001) and LFAT (r=0.45, P<0.01), but not with subcutaneous fat (r=-0.1, not significant).

CONCLUSIONS: Increased expression of 11βHSD1 in adipose may contribute to insulin resistance in patients with HAART-associated lipodystrophy.

Presenting author: J Sutinen

2003-07-08
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