Abstract
BackgroundObesity, the most common cause of insulin resistance, is increasingly recognized as a low-grade inflammatory state. Adipocyte-derived resistin is a circulating protein implicated in insulin resistance in rodents, but the role of human resistin is uncertain because it is produced largely by macrophages.Methods and FindingsThe effect of endotoxin and cytokines on resistin gene and protein expression was studied in human primary blood monocytes differentiated into macrophages and in healthy human participants.Inflammatory endotoxin induced resistin in primary human macrophages via a cascade involving the secretion of inflammatory cytokines that circulate at increased levels in individuals with obesity. Induction of resistin was attenuated by drugs with dual insulin-sensitizing and anti-inflammatory properties that converge on NF-κB. In human study participants, experimental endotoxemia, which produces an insulin-resistant state, causes a dramatic rise in circulating resistin levels. Moreover, in patients with type 2 diabetes, serum resistin levels are correlated with levels of soluble tumor necrosis factor α receptor, an inflammatory marker linked to obesity, insulin resistance, and atherosclerosis.ConclusionsInflammation is a hyperresistinemic state in humans, and cytokine induction of resistin may contribute to insulin resistance in endotoxemia, obesity, and other inflammatory states.
Highlights
Dietary and lifestyle changes during the last century have entailed an unprecedented epidemic of obesity and associated metabolic diseases, including type 2 diabetes and atherosclerosis [1]
Inflammation is a hyperresistinemic state in humans, and cytokine induction of resistin may contribute to insulin resistance in endotoxemia, obesity, and other inflammatory states
Similarities and overlap between obesity and inflammatory states are emerging. Inflammatory cytokines such as tumor necrosis factor a (TNF a) and interleukin (IL)-6 are produced by adipocytes as well as by monocytes and macrophages, and they circulate at increased levels in individuals with obesity [5,6]
Summary
Dietary and lifestyle changes during the last century have entailed an unprecedented epidemic of obesity and associated metabolic diseases, including type 2 diabetes and atherosclerosis [1]. Similarities and overlap between obesity and inflammatory states are emerging. Inflammatory cytokines such as tumor necrosis factor a (TNF a) and interleukin (IL)-6 are produced by adipocytes as well as by monocytes and macrophages, and they circulate at increased levels in individuals with obesity [5,6]. The interrelationships between obesity, insulin resistance, and atherosclerosis are of great scientific and clinical interest. The most common cause of insulin resistance, is increasingly recognized as a lowgrade inflammatory state. Adipocyte-derived resistin is a circulating protein implicated in insulin resistance in rodents, but the role of human resistin is uncertain because it is produced largely by macrophages
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