The HIV-1/HAART associated metabolic syndrome - novel adipokines, molecular associations and therapeutic implications.

The use of highly active anti-retroviral therapy has been associated with effects on various metabolic and morphological parameters that are underlied by significant hormonal and cytokine changes. Novel adipokines may have a role in the pathogenesis of these changes. In fact, leptin deficiency and hypoadiponectinemia correlate with lipoatrophy and central fat accumulation respectively whereas hypoadiponectinemia also appears to be associated with insulin resistance and lipid disorders. Preliminary evidence from proof-of-concept studies suggests that administration of recombinant leptin in replacement doses and/or administration of medications that increase adiponectin levels may improve the HIV-1/HAART associated metabolic syndrome (HAMS). Immune effects of hypoleptinemia and hypoadiponectinemia might have a role in the evolution of the HAMS that need to be further elucidated. The role for resistin in relation to HAMS is controversial and further investigation is necessary. A potential role of other novel cytokines like visfatin, retinol-binding protein-4, apelin, acylation stimulating protein, omentin and vaspin needs to be further elucidated.

Serum adiponectin and resistin in rats under three isocaloric diets: The effect of sibutramine.

The aim of the study was to investigate the effects of (1) macronutrients on food intake, body composition and serum resistin and adiponectin and (2) sibutramine(S) on the above parameters in rats fed with isocaloric diets. Three groups of male Wistar rats (n=63) were fed with high fat diet (HFD), high carbohydrate diet (HCD) or high protein diet (HPD) for 13weeks. In the last 3weeks each group was divided into three subgroups and received S 5mg/kg or 10mg/kg, or vehicle. Body weight was measured weekly, gastrocnemius muscle, perirenal, retroperitoneal and epididymal fat were isolated, fat/lean ratio was calculated and serum adiponectin and resistin were assayed. S did not affect lean body mass in any group. HFD was associated with elevated fat/lean ratio regardless of S administration. S at 10mg/Kg decreased fat/lean ratio in the HCD and HPD and adiponectin in the HFD group. S did not affect resistin in any group. Adiponectin was paradoxically elevated in the HFDS10 compared to the HCD or HPD S10 groups. Resistin was lower in the HCD compared to the HPD and HFD groups. Results suggest a preferential effect of S on body fat. The detrimental effect of S on adiponectin can be attributed to its sympathomimetic properties. Adiponectin was paradoxically elevated in the HFD and resistin in the HPD group, results that require further investigation.

Effect of isocaloric diets and sibutramine on food intake, body mass variation and serum TNF-alpha levels in rats.

BACKGROUND/AIM: The effect of isocaloric diets and sibutramine on dietary behaviour and TNF-alpha is poorly understood. The aim of the study was to investigate the effects of isocaloric diets and sibutramine on food intake, body mass variation and serum TNF-alpha in free-feeding rats. METHODS: Three groups of male Wistar rats (n = 63) were fed a high-fat diet, high-carbohydrate diet or high-protein diet for 13 weeks. In the last 3 weeks, each group was divided into 3 subgroups. Each subgroup received sibutramine 5 mg/kg, sibutramine 10 mg/kg or vehicle. Food intake was measured daily during the last week of the experiment; serum TNF-alpha was assayed and the body weight increasing rate was calculated. RESULTS: The high-fat diet was associated with increased food intake, a greater weight gain ratio and increased TNF-alpha levels. Sibutramine treatment did not affect the dietary behaviour of high-protein- or high-carbohydrate-fed rats, while it significantly attenuated the daily food intake and body weight gain rate in the high-fat group, at the dose of 10 mg/kg. TNF-alpha levels were not affected by sibutramine. CONCLUSIONS: High-fat feeding was associated with an increase in daily food intake, TNF-alpha levels and body weight gain rate, as well as with enhanced responsiveness to the anorectic effects of sibutramine. However, sibutramine did not affect TNF-alpha.