The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Interleukin-6-deficient mice develop hepatic inflammation and systemic insulin resistance
Open accessAbstract
Aims/hypothesis The role of IL-6 in the development of obesity and hepatic insulin resistance is unclear and still the subject of controversy. We aimed to determine whether global deletion of Il6 in mice (Il6 (-/-)) results in standard chow-induced and high-fat diet (HFD)-induced obesity, hepatosteatosis, inflammation and insulin resistance.Methods Male, 8-week-old Il6 (-/-) and littermate control mice were fed a standard chow or HFD for 12 weeks and phenotyped accordingly.Results Il6 (-/-) mice displayed obesity, hepatosteatosis, liver inflammation and insulin resistance when compared with control mice on a standard chow diet. When fed a HFD, the Il6 (-/-) and control mice had marked, equivalent gains in body weight, fat mass and ectopic lipid deposition in the liver relative to chow-fed animals. Despite this normalisation, the greater liver inflammation, damage and insulin resistance observed in chow-fed Il6 (-/-) mice relative to control persisted when both were fed the HFD. Microarray analysis from livers of mice fed a HFD revealed that genes associated with oxidative phosphorylation, the electron transport chain and tricarboxylic acid cycle were uniformly decreased in Il6 (-/-) relative to control mice. This coincided with reduced maximal activity of the mitochondrial enzyme β-hydroxyacyl-CoA-dehydrogenase and decreased levels of mitochondrial respiratory chain proteins.Conclusions/interpretation Our data suggest that IL-6 deficiency exacerbates HFD-induced hepatic insulin resistance and inflammation, a process that appears to be related to defects in mitochondrial metabolism.
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“The anti-inflammatory properties of IL-6 are illustrated by IL-6−/− mice, which exhibit hepatosteatosis, insulin resistance, and liver inflammation (44).”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [44]
In the citing paper
“On the other hand, in these same contexts, others have shown that IL6 induces insulin sensitivity (Carey et al., 2006; Findeisen et al., 2019; Matthews et al., 2010; Mauer et al., 2014; Steensberg et al., 2003; Timper et al., 2017), while IL6 has been shown to be insulin sensitizing in exercise (Benrick et al., 2012).”
From Origin and function of stress-induced IL-6 in murine models (2020) · cites this paper as Matthews et al., 2010
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Metadata
- Authors
- Matthews, V. B., Allen, T. L., Risis, S., Chan, M. H. S., Henstridge, D. C., Watson, N., Zaffino, L. A., Babb, J. R., Boon, J., Meikle, P. J., Jowett, J. B., Watt, M. J., Jansson, J.-O., Bruce, C. R., & Febbraio, M. A.
- Affiliations
- Baker Heart and Diabetes Institute (AU)
- Monash University (AU)
- University of Gothenburg (SE)
- Corresponding author
- Febbraio, M. A.
- ORCID
- Venue
- Diabetologia
- Published
- 2010-08-11
- Volume
- 53
- Issue
- 11
- Pages
- 2431-2441
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2089567564
- Cited by
- 334
- References
- 50
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 12 · 2023: 15 · 2022: 23 · 2021: 21 · 2020: 26 · 2019: 27 · 2018: 21 · 2017: 29 · 2016: 26 · 2015: 22 · 2014: 20 · 2013: 31 · 2012: 25
- FWCI
- 18.39
- Type
- journal article
- Language
- en
- Open access
- green
- figshare.com
- Licence
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- RMIT Research Repository (RMIT University Library) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Figshare (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- interleukin-6, hepatic insulin resistance, liver inflammation, obesity, high-fat diet, hepatic steatosis, mitochondrial metabolism, oxidative phosphorylation, beta-hydroxyacyl-CoA dehydrogenase, mitochondrial respiratory chain, liver fat deposition
- MeSH terms
- Animals, Body Composition, Calorimetry, Indirect, Diglycerides, Fatty Liver, Female, Inflammation, Insulin Resistance, Liver, Male, Mice, Inbred C57BL, Obesity, Triglycerides, Interleukin-6, Adipocytes, Mice, Knockout, Cell Size, Adiposity, Mice
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