Acute IL-6 treatment increases fatty acid turnover in elderly humans in vivo and in tissue culture in vitro

To determine whether IL-6 increases lipolysis and fat oxidation in patients with type 2 diabetes and/or whether it exerts this effect independently of changes to the hormonal milieu, patients with type 2 diabetes (D) and healthy control subjects (CON) underwent recombinant human (rh) IL-6 infusion for 3 h. Rates of appearance (R(a)) and disappearance (R(d)) of [U-(13)C] palmitate and [6,6-(2)H(2)] glucose were determined. rhIL-6 infusion increased (P<0.05) palmitate R(a) and R(d) in a similar fashion in both groups. Neither plasma glucose concentration nor glucose R(a)/R(d) was affected by rhIL-6 infusion in either group, whereas rhIL-6 infusion resulted in a reduction (P<0.05) in circulating insulin in D. Plasma growth hormone (GH) was increased (P<0.05) by IL-6 in CON, and cortisol increased (P<0.05) in response to IL-6 in both groups. To determine whether IL-6 was exerting its effect directly or through activation of these hormones, we performed cell culture experiments. Fully differentiated 3T3-L1 adipocytes were treated with PBS (control)IL-6, or IL-6 plus dexamethasone and GH. IL-6 treatment alone increased (P<0.05) lipolysis, but this effect was reduced by the addition of dexamethasone and GH such that IL-6 plus dexamethasone and GH had blunted (P<0.05) lipolysis compared with IL-6 alone. To assess whether IL-6 increases fat oxidation, L6 myotubes were treated with PBS (Control), IL-6, or AICAR, a compound known to increase lipid oxidation. Both IL-6 and AICAR markedly increased (P<0.05) oxidation of [(14)C] palmitate compared with Control. Acute IL-6 treatment increased fatty acid turnover in D patients as well as healthy CON subjects. Moreover, IL-6 appears to be activating lipolysis independently of elevations in GH and/or cortisol and appears to be a potent catalyst for fat oxidation in muscle cells.