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Review
, 2016, 7353642

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

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Review

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

Muhammad Jaffar Khan et al. J Obes.

Abstract

The aetiology of obesity has been attributed to several factors (environmental, dietary, lifestyle, host, and genetic factors); however none of these fully explain the increase in the prevalence of obesity worldwide. Gut microbiota located at the interface of host and environment in the gut are a new area of research being explored to explain the excess accumulation of energy in obese individuals and may be a potential target for therapeutic manipulation to reduce host energy storage. Several mechanisms have been suggested to explain the role of gut microbiota in the aetiology of obesity such as short chain fatty acid production, stimulation of hormones, chronic low-grade inflammation, lipoprotein and bile acid metabolism, and increased endocannabinoid receptor system tone. However, evidence from animal and human studies clearly indicates controversies in determining the cause or effect relationship between the gut microbiota and obesity. Metagenomics based studies indicate that functionality rather than the composition of gut microbiota may be important. Further mechanistic studies controlling for environmental and epigenetic factors are therefore required to help unravel obesity pathogenesis.

Figures

Figure 1
Figure 1
Modulation of bile acid circulation by gut microbiota and its effect on glucose metabolism. Concept adapted from [–8]. TGR5: G protein coupled receptor 5, VLDL: very low density lipoprotein, TG: triglycerides, GLP-1: glucagon like peptide-1, and FXR: farnesoid x receptor.
Figure 2
Figure 2
Proposed mechanism of the changes in gut hormonal axis by gut microbiota. TG: triglycerides, LPL: lipoprotein lipase, Fiaf: fasting induced adipocyte factor, ANGPTL-4: angiopoitein-like protein-4, GLP-1: glucagon like peptide-1, GPR43 and GPR41: G protein coupled receptors 43 and 41, PYY: peptide YY, and SCFA: short chain fatty acids. Minus sign indicates inhibitory effect; plus sign indicates stimulatory effect.
Figure 3
Figure 3
Proposed model for the role of LPS in generating inflammation and its relationship with obesity. Concept adapted from [–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 [–12].

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