Metabolic endotoxaemia triggers body weight gain and diabetes in mice
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Insulin resistance and low grade inflammation are characteristic features of both diabetes and obesity. In an attempt to identify a causative inflammatory factor, the authors identified bacterial lipopolysaccharide (LPS) as triggering factor. LPS, a normal membrane component of many bacteria, is also an endotoxin that may activate the secretion of proinflammatory cytokines. The authors found that normal endotoxaemia increased or decreased on a nutritional basis during the fed and fasted state. In mice, a four-week high-fat feeding (HF) chronically increased plasma LPS concentration by a factor 2-3, a threshold defined as “metabolic endotoxaemia”. In LPS-infused mice, fasting glucose, insulinaemia and weight gain were increased to a similar extent than in HF mice as were markers of inflammation and liver triglyceride content. In addition, liver – but not whole body – insulin resistance was induced as well. By contrast, CD14* mutant mice were exempt from most of LPS and HF-induced metabolic changes. Based on these results, the authors conclude that the LPS/CD14 system is involved in setting the tone of insulin sensitivity, and that variations within this system can trigger body weight gain and diabetes. In this context, lowering plasma LPS concentration could be a potent strategy for the management of both medical conditions. (*CD14 acts as a receptor for LPS.)
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