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Cited by 311Adipokines, Inflammation, and Metabolic DiseasesAdipose Tissue and MetabolismLipid metabolism and biosynthesis

Acute IL-6 Treatment Increases Fatty Acid Turnover in Elderly Humans in Vivo and in Tissue Culture in Vitro

Petersen, E. W., Carey, A. L., Sacchetti, M., Steinberg, G. R., Macaulay, S. L., Febbraio, M. A., Pedersen, B. K.·2005·American Journal of Physiology-Endocrinology and Metabolism
DOI 10.1152/ajpendo.00257.2004
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Abstract

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.

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Crossref · 10.1152/ajpendo.00257.2004

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  • Coordinated actions of IL-6 enhance metabolic flexibility by simultaneously facilitating glucose uptake and endogenous glucose production, a process thought to be a consequence of permissive effect of IL-6 on glucagon and cortisol secretion.

    “Together, these coordinated actions of IL-6 enhance metabolic flexibility by simultaneously facilitating glucose uptake and endogenous glucose production, a process thought to be a consequence of the permissive effect of IL-6 on glucagon and cortisol secretion [51].”

    From Exercise-Induced Muscle–Fat Crosstalk: Molecular Mediators and Their Pharmacological Modulation for the Maintenance of Metabolic Flexibility in Aging (2025) · cites this paper as [51]

  • In human subjects, an in vivo IL-6 infusion does not alter splanchnic glucose output.

    “However, in human subjects, an in vivo IL-6 infusion does not alter splanchnic glucose output (30,31).”

    From Signaling Specificity of Interleukin-6 Action on Glucose and Lipid Metabolism in Skeletal Muscle (2006) · cites this paper as [30]

  • When diabetes patients were given an rhIL-6 infusion, plasma insulin decreased to levels comparable with age and BMI-matched healthy controls, indicating that IL-6 enhanced insulin sensitivity.

    “When diabetes patients were given an rhIL-6 infusion, plasma concentrations of insulin decreased to levels comparable with that in age and BMI (body mass index)-matched healthy controls, indicating that the IL-6 enhanced insulin sensitivity [50].”

    From Exercise as a Mean to Control Low‐Grade Systemic Inflammation (2008) · cites this paper as [50]

  • IL-6 enhances lipolysis as well as fat oxidation.

    “A number of studies indicate that IL-6 enhances lipolysis, as well as fat oxidation [50, 58].”

    From Exercise as a Mean to Control Low‐Grade Systemic Inflammation (2008) · cites this paper as [50]

  • Infusion of rhIL-6 into healthy humans to obtain physiological concentrations increased lipolysis in the absence of hypertriacylglyceridemia or changes in catecholamines, glucagon, insulin, or adverse effects in healthy individuals and patients with type 2 diabetes.

    “Infusion of rhIL-6 into healthy humans to obtain physiological concentrations of IL-6 increased lipolysis in the absence of hypertriacylglyceridemia or changes in catecholamines, glucagon, insulin, or any adverse effects in healthy individuals as well as patients with type 2 diabetes [49, 50, 58].”

    From Exercise as a Mean to Control Low‐Grade Systemic Inflammation (2008) · cites this paper as [50]

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Authors
Petersen, E. W., Carey, A. L., Sacchetti, M., Steinberg, G. R., Macaulay, S. L., Febbraio, M. A., & Pedersen, B. K.
Affiliations
  • University of Copenhagen (DK)
  • RMIT University (AU)
  • The University of Melbourne (AU)
  • Commonwealth Scientific and Industrial Research Organisation (AU)
ORCID
Venue
American Journal of Physiology-Endocrinology and Metabolism
Publisher
American Physiological Society
Published
2005-01
Volume
288
Issue
1
Pages
E155-E162
ISSN
  • 0193-1849 (ISSN-L)
  • 1522-1555
DOI
10.1152/ajpendo.00257.2004
OpenAlex
W2145229644
Cited by
311
References
33
Citations by year
2026: 6 · 2025: 10 · 2024: 18 · 2023: 10 · 2022: 16 · 2021: 17 · 2020: 11 · 2019: 11 · 2018: 14 · 2017: 14 · 2016: 9 · 2015: 9 · 2014: 17 · 2013: 26 · 2012: 22
FWCI
9.74
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Keywords
interleukin-6, lipolysis, fat oxidation, fatty acid turnover, type 2 diabetes, adipocytes, skeletal muscle, growth hormone, cortisol, dexamethasone, insulin, AICAR, palmitate, 3T3-L1 adipocytes, L6 myotubes, older adults
MeSH terms
Aged, Animals, Blood Glucose, Diabetes Mellitus, Type 2, Fatty Acids, Nonesterified, Glycerol, Hormones, Humans, Insulin, Lipolysis, Male, Middle Aged, Triglycerides, Interleukin-6, 3T3-L1 Cells, Mice, In Vitro Techniques

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