Obesity, Inflammation, and Insulin Resistance

Harvard University, Cambridge, Massachusetts, United States
Gastroenterology (Impact Factor: 16.72). 06/2007; 132(6):2169-80. DOI: 10.1053/j.gastro.2007.03.059
Source: PubMed


Weight gain and obesity are major risk factors for conditions and diseases ranging from insulin resistance and type 2 diabetes mellitus to atherosclerosis and the sequelae of nonalcoholic fatty liver disease. A chronic, subacute state of inflammation often accompanies the accumulation of excess lipid in adipose tissue and liver (hepatic steatosis), evidenced by changes in both inflammatory cells and biochemical markers of inflammation. These changes can be seen in the involved tissues and systemically, in terms of elevated circulating levels of inflammatory markers. The link between obesity and inflammation has therefore raised the important question of whether obesity-induced inflammation plays a pathogenic role in the development and progression of these disorders. We review the rapidly expanding body of animal and clinical data that support potential roles for inflammation in the pathogenesis of insulin resistance and type 2 diabetes mellitus.

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Available from: Laura Herrero, Jan 23, 2015
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    • "These are associated with low-grade systematic inflammation , which is triggered by the activation of the immune system. Increased release of the adipocyte derived bioactive metabolites and proinflammatory cytokines also lead to the progression of disease [5] [6]. "
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    ABSTRACT: Sugar rich diet induces inflammation and insulin resistance mainly through gut microbiota alteration. Gut microflora dysbiosis increases plasma lipopolysaccharide and reduces short chain fatty acids to impair the insulin signaling cascades by different molecular pathways to progress into diabetes. Chitosan based formulations have major significance in insulin delivery system due to their ability to protect the insulin from enzymatic degradation and its efficient inter-epithelial transport. This study was designed to investigate the effect of chitosan administration on gut microflora mediated signaling pathways to prevent the diet induced diabetes. Male wistar rats were divided into non-diabetic group with a normal diet (CD), diabetic group with high sucrose diet (HSD) and treatment group with HSD and chitosan (60 mg/kg). After 8 weeks of the study, significant alterations in two major gut dominant microbial phyla i.e Firmicutes and Bacteroides and four dominant microbial species i.e. Lactobacilli, Bifidobacteria, Escherichia and Clostridia were observed in HSD group compared to CD. This microbial dysbiosis in dominant phyla was significantly prevented in chitosan administrated HSD group. Chitosan administration had also reduced the HSD induced activation of Toll like receptors and nod like receptors signaling pathways compared to HSD control group to reduce the inflammation. These suggest that chitosan can prevent the progression of Type 2 Diabetes through gut microbiota alteration, reducing endotoxin and microbes mediated inflammation.
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    ABSTRACT: Obesity is a worldwide problem that has reached epidemic proportions both in developed and developing countries. The excessive accumulation of fat poses a risk to health since it favours the development of metabolic alterations including insulin resistance and tissue inflammation, which further contribute to the progress of the complex pathological scenario observed in the obese. In this review we put together the different outcomes of fat accumulation and insulin resistance in the main insulin-responsive tissues, and discuss the role of some of the key molecular routes that control disease progression both in an organ-specific and also in a more systemic manner. In particular, we focus on the importance of studying the integrated regulation of different organs and pathways that contribute to the global pathophysiology of this condition with a specific emphasis on the role of emerging key molecular nodes such as the G protein-coupled receptor kinase 2 (GRK2) signalling hub.
    No preview · Article · Dec 2015 · Archives of Physiology and Biochemistry
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    • "control by diet alone is difficult, requiring therapy with drugs, but the adverse side effects associated with available drugs have become a limiting factor, demanding the discovery of novel molecules targeting various pathways involved in the pathogenesis of obesity (Bray, 2013). Adipose tissue is heterogeneous mix of adipocytes, preadipocytes, immune cells, and endothelium, and it responds rapidly and dynamically to alterations in nutrient excess through adipocyte hypertrophy and hyperplasia.In addition to functioning as the principal energy storage depot, adipose tissue secretes hormones that contribute to energy homeostasis(Friedman and Halaas 1998;Shoelson, Herrero et al., 2007).Thus, understanding the molecular mechanisms of adipocyte differentiation is necessaryfor designing effective drug therapies for the treatment of obesity. Several studies screening for antiobesity materials have focused to study the effect of drugs on the processes of adipocyte proliferation and differentiation(Lin, Della-Fera et al., 2005; Kim, Della- Fera et al., 2006;Yang, Della-Fera et al., 2006). "
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