In this Chapter, the metabolic syndrome is a complex disorder caused by a combination of interrelated physiological, biochemical, clinical, and metabolic factors that increases the risk of cardiovascular diseases (CVD) and type 2 diabetes mellitus. Metabolic syndrome causes an increase in the risk of developing T2D and CVD by 5-fold and 2-fold, respectively. Our body's first defense mechanism against a long-term positive energy balance (arising from high-calorie diet and sedentary lifestyle) is the storage of excess energy in adipose tissues. However, when adipose tissues no longer buffer excess calorie intakes due to prolong excess energy consumption, ectopic fat starts to accumulate in the non-adipose tissues such as the liver, muscles, and other peripheral tissues.
In this Chapter, there are three major strategies to treat metabolic syndrome, lifestyle intervention, pharmacotherapy, and bariatric surgery. Most of the gut microbes are considered commensals since they perform beneficial functions through the maintenance of the harmonic relationship with its host. Most importantly, the gut microbes also maintain the integrity of colonic mucosa. Plant-derived food rich in dietary fibre undergoes microbial fermentation in the colon resulting in the formation of SCFA by specific groups of gut microbes. The highest SCFA concentration is found in the proximal colon, and the SCFA levels decrease towards the distal colon. The production of SCFA by gut microbes enables the extraction of carbon sources from dietary fibre, which are undigested in the upper GI tract. SCFA contributed to 5~15% of the total caloric requirement of a human. More importantly, SCFA also acts as signaling molecules that modulate various host metabolic processes and thus host physiology, and contribute to health and diseases. Also, SCFA is ligands for free fatty acid receptors (FFARs), types of G protein-coupled receptors (GPCRs).
One of the most critical roles exerted by microbiota is to modulate a wide of array of host metabolic processes, which plays a significant role in the development of metabolic syndrome. Also, a study has shown that the germ-free mice that received faecal transplant from obese mice exhibited obese phenotypes. Also, the bacterial fermentation products, SCFA, appear to play a critical role in this microbial modulation of host metabolism. The gut microbes exert its roles in the regulation of glucose homeostasis through the production of SCFA. Butyrate not only stimulates insulin secretion in pancreatic ss cells, through upregulating GLP-1 secretion but also confers protective roles. Besides downregulating the blood glucose levels via GLP-1 dependent pathway, butyrate also positively influence glucose homeostasis by upregulating the intestinal gluconeogenesis. Various mechanisms have evolved to modulate energy intake and energy expenditure, which are essential to maintain body weight and for the survival of organisms. A microbial metabolite, acetate, can cross the blood-brain barrier and reach the hypothalamus where acetate either is metabolized by the brain or stimulates appetite suppression, which results in decreased food intake.
Conclusion
The endocannabinoid system is ubiquitously expressed throughout our bodies and play various physiological functions including the regulation of host energy metabolism. The recent reviews propose the modulation of gut microbiota through the administration of probiotics could be a promising therapeutic approach for the management of metabolic syndrome. Several strains of lactic acid bacteria have been genetically modified to secrete anti-inflammatory compounds to target intestinal bowl diseases (IBD). IBD is characterized by severe chronic intestinal inflammation caused by defective innate and adaptive immune regulations. The prevalence of metabolic syndrome has been increasing during the last three decades where currently more than a billion people are suffering from this disease. Thus, there is a pressing need to develop a new therapeutic approach that overcomes the limitations of the currently available strategies to fight the global epidemic of metabolic syndrome.
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