Interleukin-6 stimulates lipolysis and fat oxidation in humans
Open accessAbstract
Although IL-6 is a key modulator of immune function, it also plays a role in regulating substrate metabolism. To determine whether IL-6 affects lipid metabolism, 18 healthy men were infused for 3 h with saline (Con; n = 6) or a high dose (High-rhIL6; n = 6) or a low dose (Low-rhIL6; n = 6) of recombinant human IL-6 (rhIL-6). The IL-6 concentration during Con, Low-rhIL6, and High-rhIL6 was at a steady state after 30 min of infusion at approximately 4, 140, and 320 pg/ml, respectively. Either dose of rhIL-6 was associated with a similar increase in fatty acid (FA) concentration and endogenous FA rate of appearance (R(a)) from 90 min after the start of the infusion. The FA concentration and FA R(a) continued to increase until the cessation of rhIL-6 infusion, reaching levels approximately 50% greater than Con values. The elevated levels reached at the end of rhIL-6 infusion persisted at least 3 h postinfusion. Triacylglycerol concentrations were unchanged during rhIL-6 infusion, whereas whole body fat oxidation increased after the second hour of rhIL-6 infusion. Of note, during Low-rhIL6, the induced elevation in FA concentration and FA R(a) occurred in the absence of any change in adrenaline, insulin, or glucagon, and no adverse side effects were observed. In conclusion, the data identify IL-6 as a potent modulator of fat metabolism in humans, increasing fat oxidation and FA reesterification without causing hypertriacylglyceridemia.
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By directly promoting lipolysis and mediating metabolic adaptation to exercise in skeletal muscle, IL-6 favors glucose disposal, ultimately resulting in skeletal muscle effectively utilizing free fatty acids derived from visceral adipose tissue lipolysis and decreased available lipogenic substrate.
“By directly promoting lipolysis and mediating metabolic adaptation to exercise in SkM [75], IL-6 favors glucose disposal, which ultimately results in SkM effectively utilizing FFAs derived from VAT lipolysis and decreased available lipogenic substrate.”
From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [75]
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredIrisin, IL-15, and IL-6 directly induce lipolysis in adipocytes.
“For instance, irisin [58], IL-15 [89], and IL-6 [75] have shown to directly induce lipolysis in adipocytes (2a)”
IL-6 mediates lipid oxidation, induces production of anti-inflammatory interleukins during exercise, and stimulates muscle growth.
“For instance, the pro-inflammatory cytokine IL-6 mediates lipid oxidation [7], induces the production of anti-inflammatory interleukins during exercise (e.g. IL-10 and IL-1ra) [8] and stimulates muscle growth [9].”
IL-6 can increase intramyocellular or whole body fatty acid oxidation via AMPK activation.
“Several other studies have described that IL-6 can increase intramyocellular (58-60) or whole body (61) fatty acid oxidation via AMPK activation (58, 62).”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [61]
A separate human study found that IL-6 infusion stimulates lipolysis and lipid oxidation.
“However, another study of IL-6 infusion into humans found that IL-6 stimulates lipolysis and lipid oxidation54,121.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [121]
In vivo experiments in humans indicate that IL-6 infusion stimulates lipolysis and rates of whole-body fat oxidation.
“In vivo experiments in humans indicates that IL-6 infusion stimulates lipolysis and rates of whole-body fat oxidation(36), suggesting that IL-6 is a regulator of whole-body lipid metabolism.”
From Signaling Specificity of Interleukin-6 Action on Glucose and Lipid Metabolism in Skeletal Muscle (2006) · cites this paper as [36]
IL-6 infusion in humans is correlated with increased lipolysis and fat oxidation.
“IL-6 infusion in humans is correlated with increased lipolysis and fat oxidation (36), providing clinical support for a role of IL-6 in lipid metabolism.”
From Signaling Specificity of Interleukin-6 Action on Glucose and Lipid Metabolism in Skeletal Muscle (2006) · cites this paper as [36]
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 [58]
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 [58]
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“An acute increase in IL-6 concentrations is believed to enhance whole-body lipolysis and β-oxidation (van Hall et al., 2003).”
BackgroundHealth benefits of exercise — more than meets the eye!
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Self-citationTumor Necrosis Factor-α Modulates Human<i>in Vivo</i>Lipolysis
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Self-citationRegulation of Energy Metabolism by Bone-Derived Hormones
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The Role of the Skeletal Muscle Secretome in Mediating Endurance and Resistance Training Adaptations
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“In adipocytes, IL-6 induces lipolysis and free fatty acid oxidation [8,9].”
BackgroundAltered Response of Skeletal Muscle to IL-6 in Type 2 Diabetic Patients
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Looking on the “brite” side exercise-induced browning of white adipose tissue
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- Authors
- van Hall, G., Steensberg, A., Sacchetti, M., Fischer, C., Keller, C., Schjerling, P., Hiscock, N., Møller, K., Saltin, B., Febbraio, M. A., & Pedersen, B. K.
- Affiliations
- University of Copenhagen (DK)
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2003-07
- Volume
- 88
- Issue
- 7
- Pages
- 3005-3010
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2112857693
- Cited by
- 767
- References
- 20
- Citations by year
- 2026: 23 · 2025: 38 · 2024: 54 · 2023: 37 · 2022: 47 · 2021: 35 · 2020: 39 · 2019: 23 · 2018: 23 · 2017: 23 · 2016: 30 · 2015: 31 · 2014: 30 · 2013: 38 · 2012: 35
- FWCI
- 23.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- RMIT Research Repository (RMIT University Library) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Sundhed og Sygdom, Det Frie Forskningsråd
- Danmarks Grundforskningsfond (504–14)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- interleukin-6, lipolysis, fat oxidation, fatty acid content, triglycerides, lipid metabolism, substrate metabolism, hypertriglyceridemia
- MeSH terms
- Adult, Energy Metabolism, Epinephrine, Fatty Acids, Glucagon, Glycerol, Humans, Hydrocortisone, Insulin, Lipolysis, Male, Norepinephrine, Oxidation-Reduction, Oxygen Consumption, Recombinant Proteins, Triglycerides, Interleukin-6
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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