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 (Ra) and disappearance (Rd) of [U-(13C)]palmitate and [6,6-(2H2)]glucose were determined. rhIL-6 infusion increased (P < 0.05) palmitate Ra and Rd in a similar fashion in both groups. Neither plasma glucose concentration nor glucose Ra/Rd 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.
Petersen
E W
EW
Copenhagen Muscle Research Center, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Carey
A L
AL
Sacchetti
M
M
Steinberg
G R
GR
Macaulay
S L
SL
Febbraio
M A
MA
Pedersen
B K
BK
D041721:3T3-L1 Cells; D000368:Aged; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005990:Glycerol / Q000097:blood; D006728:Hormones / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood; D015850:Interleukin-6 / Q000008:administration & dosage* / Q000097:blood; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D051379:Mice; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D006728:Hormones; D007328:Insulin; D015850:Interleukin-6; D014280:Triglycerides; D005990:Glycerol