Acute reduction of lipolysis reduces adiponectin and IL-18: evidence from an intervention study with acipimox and insulin

AIMS/HYPOTHESIS: Low-grade inflammation is a feature of chronic diseases such as type 2 diabetes and lipodystrophy. It is associated with abdominal adiposity, increased levels of NEFA, hyperinsulinaemia and low adiponectin levels. However, the causal relationship between impaired metabolism and inflammation is not understood. We explored the anti-lipolytic effect of acipimox and insulin on adiponectin and adipocyte-associated cytokines in patients with lipodystrophy. METHODS: In a randomised placebo-controlled crossover design using nine patients with non-diabetic, HIV-associated lipodystrophy, we assessed whether (1) overnight administration of a low dose of acipimox and/or (2) insulin-induced suppression of NEFA flux altered circulating plasma levels of adiponectin, IL-18, TNF-α and IL-6 in the basal condition and in a two-stage euglycaemic–hyperinsulinaemic clamp combined with stable isotopes (insulin infusion rates 20 mU m(−2) min(−1) and 50 mU m(−2) min(−1)). RESULTS: Insulin decreased plasma NEFA in a dose-dependent manner (p < 0.0001). Acipimox reduced basal plasma NEFAs and plasma NEFAs during the low-dose insulin infusion compared with placebo (p < 0.0001 for acipimox effect). Plasma adiponectin and plasma IL-18 were reduced during both situations where lipolysis was inhibited (p < 0.0001 for acipimox effect; p < 0.0001 and p < 0.05 for insulin effect on plasma adiponectin and plasma IL-18, respectively). In contrast, plasma IL-6 and plasma TNF-α did not change during low NEFA concentrations. CONCLUSIONS/INTERPRETATION: Using two different tools to manipulate lipolysis, the present study found that acute inhibition of lipolysis reduces levels of adiponectin and IL-18 in patients with HIV-associated lipodystrophy.