New-found link between microbiota and obesity

Abstract

Due to the grave pathological role of obesity, worldwide research is being continued to find out the causative factors involved in it. Recent advances in this field reveal a possible relationship between the compositional pattern of gut microbiota and genesis of obesity. Several study results have shown that short-chain fatty acids (SCFAs, microbiota-induced fermentation products) and lipopolysaccharides (LPS, an integral component of Gram negative microorganisms) play the key role in linking the two. Though several SCFAs are produced as microbiota-fermentation products, three of them, i.e., butyrate, propionate and acetate have been found to be definitely involved in obesity; though individually they are neither purely obesogenic nor antiobesogenic. Out of these, butyrate and propionate are predominantly antiobesogenic. Butyrate, though a major energy source for colonocytes, has been found to increase mitochondrial activity, prevent metabolic endotoxemia, improve insulin sensitivity, possess anti-inflammatory potential, increase intestinal barrier function and protect against diet-induced obesity without causing hypophagia. Propionate has been found to inhibit cholesterol synthesis, thereby antagonizing the cholesterol increasing action of acetate, and to inhibit the expression of resistin in adipocytes. Moreover, both these SCFAs have been found to cause weight regulation through their stimulatory effect on anorexigenic gut hormones and to increase the synthesis of leptin. Unlike butyrate and propionate, acetate, which is substantially absorbed, shows more obesogenic potential, as it acts as a substrate for hepatic and adipocyte lipogenesis. High fat diet increases the absorption of LPS, which, in turn, has been found to be associated with metabolic endotoxemia and to induce inflammation resulting in obesity. Multiple independent and interrelated mechanisms have been found to be involved in such linking processes which are discussed in this review work along with some possible remedial measures for prevention of weight gain and obesity.

Keywords: Microbiota; Obesity; Butyrate; Propionate; Acetate

Core tip: The objective of this article is to relate gastrointestinal microbiota with obesity positively. This idea itself is most innovative. In this article, probable mechanisms involved in relating microbiota with obesity have been discussed. Its key findings are: (1) The gut microbiota play a definite role both in genesis and retardation of obesity; (2) Microbiota-derived lipopolysaccharides and short-chain fatty acids mediate the obesogenic action; (3) Fatty diet not only adds calories but also shifts microbiota compositional pattern in favour of obesity; and (4) The obesogenic actions are mediated through receptor activation, modification of cytokine and endocrine function and gene expression.