Acute administration of IL-6 improves indices of hepatic glucose and insulin homeostasis in lean and obese mice
| Autor: | Logan K. Townsend, Matthew R. Panasevich, Grace M. Meers, Willem T. Peppler, R. Scott Rector, Rebecca E. K. MacPherson, David C. Wright |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Hepatic glucose Physiology medicine.medical_treatment Diet High-Fat 03 medical and health sciences 0302 clinical medicine Physiology (medical) Internal medicine Gene expression medicine Animals Homeostasis Insulin Obesity Interleukin 6 Obese Mice Hepatology biology Interleukin-6 business.industry Gastroenterology Single injection Glucose Tolerance Test Lipid Metabolism medicine.disease Mice Inbred C57BL Glucose 030104 developmental biology Endocrinology Liver Hepatocytes biology.protein 030211 gastroenterology & hepatology Insulin Resistance business |
| Zdroj: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 316:G166-G178 |
| ISSN: | 1522-1547 0193-1857 |
| DOI: | 10.1152/ajpgi.00097.2018 |
| Popis: | Obesity can lead to impairments in hepatic glucose and insulin homeostasis, and although exercise is an effective treatment, the molecular targets remain incompletely understood. As IL-6 is an exercise-inducible cytokine, we aimed to identify whether IL-6 itself influences hepatic glucose and insulin homeostasis and whether this response differs during obesity. In vivo, male mice were fed a low-fat diet (LFD; 10% kcal) or a high-fat diet (HFD; 60% kcal) for 7 wk, which induced obesity and hepatic lipid accumulation. LFD- and HFD-fed mice were injected with IL-6 (400 ng, 75 min) or PBS and then with insulin (1 U/kg; ~15 min) or saline, at which point livers were collected. In both LFD- and HFD-fed mice, IL-6 decreased blood glucose and mRNA expression of gluconeogenic genes alongside increased phosphorylation of AKT in comparison to PBS controls, and this occurred without changes in circulating insulin. To determine whether this effect of IL-6 was directly on the liver, we completed in vitro isolated primary hepatocyte experiments from chow-fed mice and cultured with or without exposure to free fatty acid (250 μm palmitate and 250 μm oleate, 24 h) to induce lipid accumulation. In both control and free fatty acid-treated hepatocytes, IL-6 (20 ng/ml, 75 min) slightly attenuated insulin-stimulated (10 nM; ~15 min) AKT phosphorylation. Together, these data suggest that IL-6 may lead to improvements in indices of hepatic glucose and insulin homeostasis in vivo; however, this is likely due to an indirect effect on the hepatocyte. NEW & NOTEWORTHY In this study, we used lean and obese mice and found that a single injection of IL-6 improved glucose tolerance, decreased hepatic gluconeogenic gene expression, and increased hepatic phosphorylation of AKT. In primary hepatocytes cultured under control and lipid-laden conditions, IL-6 had a mild, but deleterious, effect on phosphorylation of AKT. Our results show that the beneficial effects of IL-6 on glucose and insulin homeostasis, in vivo, are maintained in obesity. |
| Databáze: | OpenAIRE |
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