Gut Microbiota and Metabolic Health: The Potential Beneficial Effects of a Medium Chain Triglyceride Diet in Obese Individuals

Abstract

Obesity and associated metabolic complications, such as non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D), are in constant increase around the world. While most obese patients show several metabolic and biometric abnormalities and comorbidities, a subgroup of patients representing 3% to 57% of obese adults, depending on the diagnosis criteria, remains metabolically healthy. Among many other factors, the gut microbiota is now identified as a determining factor in the pathogenesis of metabolically unhealthy obese (MUHO) individuals and in obesity-related diseases such as endotoxemia, intestinal and systemic inflammation, as well as insulin resistance. Interestingly, recent studies suggest that an optimal healthy-like gut microbiota structure may contribute to the metabolically healthy obese (MHO) phenotype. Here, we describe how dietary medium chain triglycerides (MCT), previously found to promote lipid catabolism, energy expenditure and weight loss, can ameliorate metabolic health via their capacity to improve both intestinal ecosystem and permeability. MCT-enriched diets could therefore be used to manage metabolic diseases through modification of gut microbiota.

Association between body mass index and Firmicutes/Bacteroidetes ratio in an adult Ukrainian population

“…There are: (1) increased caloric intake from indigestible polysaccharides, combined with effect on hepatic de novo lipogenesis via carbohydrate and sterol response-element binding proteins; (2) enhanced cellular uptake of fatty acids and storage of triglycerides in adipocytes via suppression of intestinal expression of fasting-induced adipocyte factor which is circulating inhibitor of lipoprotein lipase; (3) suppression the skeletal muscle fatty acid oxidation through a metabolic pathway involving phosphorylation of adenosine monophosphate-activated protein kinase; and (4) interaction between short chain fatty acids products of microbial fermentation of dietary polysaccharides and G-protein-coupled receptor 41 which results in increased levels of enteroendocrine cell-derived hormone PYY, thus, reducing gut motility with subsequently increased intestinal transit time and absorption rate of short-chain fatty acids [7–9]. Microbiota can also promote obesity and metabolic syndrome by inducing low-grade inflammation [7, 10]. Currently, gut microbiota is increasingly considered as a “metabolic organ” greatly affecting the organism’s metabolism [11].…”

Cooperative Cobinding of Synthetic and Natural Ligands to the Nuclear Receptor PPARγ

“…We solved the crystal structure of the PPARγ LBD bound to edaglitazone at the orthosteric pocket, which unexpectedly revealed a bacterial MCFA cobound to the alternate site. MCFAs are not only present in bacteria; they are also dietary mammalian natural PPARγ ligands obtained from foods such as oils and dairy products (31) that display high serum concentrations (µM-mM) and activate PPARγ transcription, regulate the expression of PPARγ target genes, and influence cellular differentiation, adipogenesis, and insulin sensitization in mice (15,32,33). The cobound MCFA provides a "ligand link" to the flexible Ω-loop, and crystal structures of PPARγ bound to covalent orthosteric antagonists revealed that synthetic ligands extensions within the orthosteric pocket can push fatty acid cobinding modes towards the Ω-loop.…”

Strategies to increase the efficacy of using gut microbiota for the modulation of obesity

“…In addition to carbohydrates and lipids, the relative amount of dietary nitrogen was found to fundamentally shape the gut microbiota structure and influence healthy host-microbiome outcomes (32,33). Some minor molecules in diets, such as polyphenols, flavonoids and medium-chain triglycerides, are also able to shift gut microbiota and consequently alleviate obesity (34)(35)(36)(37)(38)(39).…”