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

• Published in: American journal of physiology: endocrinology and metabolism 2005-01, Vol.288 (1), p.E155-E162
• Main Authors: Petersen, E. W, Carey, A. L, Sacchetti, M, Steinberg, G. R, Macaulay, S. L, Febbraio, M. A, Pedersen, B. K
• Format: Article
• Language: English
• Subjects: 3T3-L1 Cells; Aged; Animals; Blood Glucose - metabolism; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Fatty Acids, Nonesterified - blood; Glycerol - blood; Hormones - blood; Humans; In Vitro Techniques; Insulin - blood; Interleukin-6 - administration & dosage; Interleukin-6 - blood; Lipolysis - drug effects; Male; Mice; Middle Aged; Triglycerides - blood
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00257.2004

1 Copenhagen Muscle Research Centre and 2 Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Denmark; 3 Skeletal Muscle Research Laboratory, Center for Nutrition Metabolism and Endocrinology, Royal Melbourne Institute of Technology University, Bundoora; 4 St. Vincent’s Institute of Medical Research, University of Melbourne, Fitzroy; and 5 Commonwealth Scientific and Industrial Organisation Health Sciences and Nutrition, Parkville, Australia Submitted 15 June 2004 ; accepted in final form 20 August 2004 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. cytokines; metabolism; insulin sensitivity Address for reprint requests and other correspondence: B. K. Pede