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Interleukin-6-deficient mice develop hepatic inflammation and systemic insulin resistance.
V B Matthews1, T L Allen, S Risis
1Cellular and Molecular Metabolism Laboratory, Baker IDI Heart & Diabetes Institute, PO Box 6492, St Kilda Road Central, Melbourne, 3008, VIC, Australia.
Diabetologia
|August 11, 2010
Summary
Interleukin-6 (IL-6) deficiency worsens high-fat diet-induced obesity and liver inflammation in mice. This exacerbation is linked to impaired mitochondrial metabolism and function, highlighting IL-6
Area of Science:
- Metabolic diseases
- Immunology
- Mitochondrial biology
Background:
- The role of Interleukin-6 (IL-6) in obesity and hepatic insulin resistance is controversial.
- Understanding IL-6's impact is crucial for developing targeted therapies for metabolic disorders.
Purpose of the Study:
- To investigate the effect of global Interleukin-6 (IL-6) gene deletion (Il6 (-/-)) on diet-induced obesity.
- To determine the impact of IL-6 deficiency on hepatic insulin resistance, hepatosteatosis, and liver inflammation.
- To elucidate the role of mitochondrial metabolism in IL-6's influence on metabolic health.
Main Methods:
- Phenotyping of male, 8-week-old Il6 (-/-) mice and littermate controls fed standard chow or high-fat diet (HFD) for 12 weeks.
- Assessment of body weight, fat mass, liver steatosis, inflammation, and insulin resistance.
- Gene expression analysis (microarray) of liver tissues and measurement of mitochondrial enzyme activity and protein levels.
Main Results:
- Il6 (-/-) mice exhibited obesity, hepatosteatosis, liver inflammation, and insulin resistance on a standard chow diet compared to controls.
- Both Il6 (-/-) and control mice showed similar weight gain and fat deposition on HFD, but Il6 (-/-) mice had persistent liver inflammation and insulin resistance.
- HFD-fed Il6 (-/-) mice displayed decreased expression of genes involved in oxidative phosphorylation and mitochondrial function, alongside reduced mitochondrial enzyme activity and protein levels.
Conclusions:
- Interleukin-6 (IL-6) deficiency exacerbates high-fat diet-induced hepatic insulin resistance and inflammation.
- Impaired mitochondrial metabolism, including reduced oxidative phosphorylation and electron transport chain function, is implicated in this exacerbation.
- These findings suggest a critical role for IL-6 in maintaining metabolic homeostasis and mitigating diet-induced liver damage.
