IL-6 and IL-8 are cytokines secreted by adipose tissue. IL-6 is pro-inflammatory and involved in host defense mechanisms. Ann Intern Med. 1998 Jan 15;128(2):127-37 Up to 25% of circulating IL-6 may be produced by adipose tissue, while other contributing sites include immune cells, fibroblasts, endothelial cells, and skeletal muscle. IL6 secretion is greater from visceral adipose tissue compared to subcutaneous tissues. J Clin Endocrinol Metab. 1998 Mar;83(3):847-50 with stromal immune cells contributing more than adipocytes. IL6 levels independently correlates with BMI and fasting insulin resistance index. Obes Res. 2001 Jul;9(7):414-7. and can predict development of type 2 diabetesJAMA. 2001 Jul 18;286(3):327-34 and myocardial infarctions Circulation. 2000 Apr 18;101(15):1767-72 . IL-6 gene polymorphisms also correlate with insulin resistance. Hum Genet. 2003 Apr;112(4):409-13 Weight loss results in significant reduction of IL-6 levels in adipose tissue and serum. J Clin Endocrinol Metab. 2000 Sep;85(9):3338-42 TNF alpha may control the secretion of IL-6 by adipose tissue.
IL-6 contributes to hepatic insulin resistance development through inhibition of insulin receptor signal transduction partly by induction of suppressor of cytokine signalling-3 (SOCS-3). J Biol Chem. 2003 Apr 18;278(16):13740-6 IL 6 reduces the activity of lipoprotein lipase (thus decreasing the availability of intracellular substrate for triglyceride synthesis). IL6 may also regulate thermogenesis and estrogen metabolism. IL6 increases lipolysis and NEFA release. IL-6 decreases Adiponectin secretion contributing to a decrease in insulin sensitivity. Biochem Biophys Res Commun. 2003 Feb 21;301(4):1045-50 IL-6 administration to healthy people results in dose-dependent hyperglycaemia due to increased insulin resistance, J Clin Endocrinol Metab. 1997 Dec;82(12):4167-70 although variable results with IL-6 administration have been demonstrated with no impairment of endogenous glucose production, whole-body glucose disposal or glucose uptake in healthy individuals. J Physiol. 2003 Apr 15;548(Pt 2):631-8 On a similar note, mice deficient in IL-6 were not protected against development of obesity or glucose intolerance. Nat Med. 2002 Jan;8(1):75-9
IL-8 exerts a direct effect on endothelial cells to attract monocytes and promote vascular smooth muscle cell migration. This might account for the link between adiposity, cytokine secretion and vascular disease. Targeting these cytokines may provide a means to improve insulin sensitivity.
IL-6 contributes to hepatic insulin resistance development through inhibition of insulin receptor signal transduction partly by induction of suppressor of cytokine signalling-3 (SOCS-3). J Biol Chem. 2003 Apr 18;278(16):13740-6 IL 6 reduces the activity of lipoprotein lipase (thus decreasing the availability of intracellular substrate for triglyceride synthesis). IL6 may also regulate thermogenesis and estrogen metabolism. IL6 increases lipolysis and NEFA release. IL-6 decreases Adiponectin secretion contributing to a decrease in insulin sensitivity. Biochem Biophys Res Commun. 2003 Feb 21;301(4):1045-50 IL-6 administration to healthy people results in dose-dependent hyperglycaemia due to increased insulin resistance, J Clin Endocrinol Metab. 1997 Dec;82(12):4167-70 although variable results with IL-6 administration have been demonstrated with no impairment of endogenous glucose production, whole-body glucose disposal or glucose uptake in healthy individuals. J Physiol. 2003 Apr 15;548(Pt 2):631-8 On a similar note, mice deficient in IL-6 were not protected against development of obesity or glucose intolerance. Nat Med. 2002 Jan;8(1):75-9
IL-8 exerts a direct effect on endothelial cells to attract monocytes and promote vascular smooth muscle cell migration. This might account for the link between adiposity, cytokine secretion and vascular disease. Targeting these cytokines may provide a means to improve insulin sensitivity.