Role of Gut Microbiota in the Aetiology of Obesity: Proposed Mechanisms and Review of the Literature

Figure 3

Proposed model for the role of LPS in generating inflammation and its relationship with obesity. Concept adapted from [9–12]. Altered mucosal barrier function due to reduced expression of glucagon like peptides 1 and 2 (GLP-1 and GLP-2) leads to altered mucosal function and reduced synthesis of tight junction proteins, Zonula Occludin-1 and Zonula Occludin-2 (ZO-1, ZO-2), increasing gut permeability. This allows LPS to enter the systemic circulation inducing the release of proinflammatory cytokines. Proinflammatory cytokines result in activation of a family of kinases JNK and IKK (inhibitor of NFkB kinase) that increase the expression of inflammatory and lipid metabolism genes. Subcutaneous administration of LPS, hyperglycaemia, and insulin resistance induces the same pathway by increasing the endoplasmic reticulum and mitochondrial stress. Type-2 diabetes, hyperglycaemia, and insulin resistance also cause macrophage infiltration and inflammatory cytokine release leading to the same process. HF: high fat diet [9–12].