Acute effect of intravenous corticotropin releasing hormone on local adipose tissue metabolism in vivo

Corticotropin releasing hormone (CRH) plays an important role in the complex system of energy metabolism and weight control. The anorectic effect of CRH has been attributed to its various actions in the central nervous system. Additionally, CRH receptors have been identified in peripheral organs including brown and white adipose tissue. The functional role of CRH in adipose tissue metabolism in vivo in humans is still poorly understood.

We evaluated the effects of intravenously injected CRH on adipose tissue metabolism and blood flow in healthy humans in a double-blinded, placebo controlled, cross-over design. Interstitial fluid for determination of glycerol, lactate and glucose was sampled in the femoral subcutaneous adipose tissue using microdialysis in 12 healthy volunteers before and after intravenous injection of CRH 1µg/kg or placebo. In parallel, changes in local tissue blood flow were monitored with laser-Doppler flowmetry and, additionally, in 5 subjects receiving CRH sympathetic nerve activity to the lateral femoral region was microneurographically determined within the lateral superficial femoral nerve. Injection of CRH induced an acute increase of interstitial concentrations of glycerol (19.0±5.4%, p<0.05), lactate (20.2±5.8%, p<0.001) and glucose (13.5±5.8%, p<0.05) all reaching their peak level 15 minutes after the injection. Plasma levels of lactate and glucose remained unaffected while glycerol and FFA were elevated by 16.7%±5.9 and 13.6±5.3 after 15min (p<0.05) respectively. Blood flow changes did not explain interstitial metabolite alterations. Initial CRH effects on adipose tissue metabolism were short lasting and disappeared after 15min. CRH had no effect on skin sympathetic nerve activity. The peak of interstitial glycerol release was earlier than the maximum level of serum cortisol, suggesting a direct effect of CRH on adipocyte metabolism. The present study underlines the importance of CRH on energy metabolism in humans. CRH injection immediately increases interstitial fat tissue concentrations of glycerol, lactate and glucose. This cannot be explained by the rise in serum cortisol or changes in tissue perfusion. CRH acutely increased skin blood flow but this vasodilatory effect is restricted to the epidermis and leaves adipose tissue blood flow unaffected. Thus, our study shows that CRH is metabolic active and involves both in lipolysis and glucose metabolism in human adipose tissue. This effect is probably mediated by peripheral CRH receptors on the fat cell.