Deletion of interleukin-6 improves pyruvate tolerance without altering hepatic insulin signaling in the leptin receptor-deficient mouse

Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA.
Metabolism: clinical and experimental (Impact Factor: 3.89). 05/2011; 60(11):1610-9. DOI: 10.1016/j.metabol.2011.04.004
Source: PubMed


Obesity is associated with increased circulating interleukin-6 (IL-6), which may contribute to hepatic insulin resistance by impairing insulin receptor signaling. This study was designed to assess the impact of the systemic absence of IL-6 on the development of insulin resistance and glucose intolerance in an obese mouse model. Systemic insulin, glucose, and pyruvate tolerance tests were performed in IL-6 knockout (IL6KO) mice that had been crossed with a genetically obese (leptin receptor-deficient mouse model [Lep(db)]) mouse model. Real-time reverse transcriptase polymerase chain reaction and Western blot analysis assessed cellular and molecular markers of insulin signaling, inflammation, and metabolism. Absence of IL-6 did not improve systemic glucose or insulin tolerance, but Lep(db) × IL6KO mice displayed a smaller blood glucose increase following a pyruvate challenge. These results suggest that loss of IL-6 in the context of obesity may locally reduce hepatic glucose production from a gluconeogenic precursor. Hepatic insulin-dependent insulin receptor autophosphorylation, Akt activation, and FoxO1 phosphorylation were similar between Lep(db) × IL6KO mice and Lep(db) controls. Basal gene expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase was reduced in male Lep(db) × IL6KO mice relative to Lep(db) controls; but gene expression of another regulatory enzyme, glucose-6-phosphatase, remained unaltered. Absence of IL-6 reduced gene expression of serum amyloid A and RelA in female Lep(db) mice, but did not alter hepatic triglyceride accumulation or lipogenic gene expression. Overall, our results suggest that IL-6 may be detrimental in obesity by contributing to elevated hepatic glucose output.

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Available from: Leonidas G Koniaris, Feb 25, 2015
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    • "Each mouse was weighed before fracture and again at sacrifice. Glucose tolerance testing (GTT) was performed on representative lean (n = 5) and HFD-fed (n = 5) mice preoperatively [24], [25]. Briefly, mice were fasted for 6 hours, anesthetized with isoflurane (5%) and tail vein blood was sampled using a commercially available glucometer (One Touch Ultra; Lifescan, Inc., Milpitas, CA, USA). "
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    Full-text · Article · Jun 2014 · PLoS ONE
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    • "Clementi et al. [5] reported that lack of IL-6 enhanced pyruvate tolerance and attenuated hepatic inflammation without making a significant difference in insulin signaling. "

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