The role of gut microbiota in the development of obesity: molecular mechanisms and therapeutic implications

Abstract

Dramatičan porast prevalence gojaznosti u populaciji dece i adolescenata predstavlja vodeći zdravstveni problem savremenog društva. Prema dosadašnjim istraživanjima, glavni oblik dijetetskog lečenja gojaznosti kod dece i adolescenata predstavlja uravnotežena hipokalorijska ishrana koju karakteriše povećan unos hrane koja sadrži vlakna, pre svega voće, povrće i cela zrna žitarica. Kako se sastav crevne mikrobiote menja u zavisnosti od režima ishrane, brojne studije su pokazale postojanje veze između sastava mikrobiote u fecesu gojaznih i njihove telesne težine. Imajući to na umu nameće se pitanje da li je smanjenje gojaznosti nakon hipokalorijske ishrane posledica promena u količini i sastavu crevne mikrobiote i produkata njene aktivnosti kao što su masne kiseline kratkog lanca (eng. Short chain fatty acid, SCFA). Masne kiseline kratkog lanca, pre svega sirćetna, propionska i buterna, nastaju procesom fermentacije nerastvorljivih biljnih vlakana u debelom crevu od strane crevne mikrobiote, a pored uloge u održavanja crevne homeostaze svoju biološku funkciju ostvaruju i kao signalni molekuli koji modulišu metabolizam lipida u masnom tkivu. Interesantno je da u zavisnosti od tipa i zastupljenosti, masne kiseline kratkog lanca mogu da stimulišu kako proces lipolize, tako i procese adipogeneze i lipogeneze. U procesu regulacije lipolize glavnu ulogu ima enzim HSL (eng. hormone sensitive lipase), dok su ključni regulatori procesa adipo- i lipogeneze u masnom tkivu transkripcioni regulatori PPARγ (eng. peroxisome proliferator-activated receptor γ), SREBP-1 (eng. sterol regulatory element binding protein-1) i ChREBP (eng. carbohydrate response element binding protein). Rasvetljavanje molekularnih mehanizama delovanja masnih kiselina kratkog lanca na ćelije masnog tkiva, pre svega na procese regulacije adipogeneze i lipidnog metabolizma može doprineti uspešnijoj prevenciji i lečenju gojaznosti putem promena u sastavu crevne mikrobiote i njenih produkata koje se mogu kontrolisati različitim režimima ishrane.

The dramatic increase in the prevalence of obesity in the population of children and adolescents represents the leading health problem of modern society. According to previous research, the main form of dietary treatment of obesity in children and adolescents is a balanced hypocaloric diet characterized by an increased intake of food containing fiber, primarily fruits, vegetables and whole grains. As the composition of the intestinal microbiota changes depending on the diet, numerous studies have shown the existence of a relationship between the composition of the microbiota in the feces of obese people and their body weight. Bearing this in mind, the question arises whether the reduction of obesity after a hypocaloric diet is a consequence of changes in the amount and composition of the intestinal microbiota and the products of its activity, such as short chain fatty acids (SCFA). Short-chain fatty acids, primarily acetic, propionic and butyric, are produced by the process of fermentation of insoluble plant fibers in the large intestine by intestinal microbiota, and in addition to their role in maintaining intestinal homeostasis, they also perform their biological function as signaling molecules that modulate lipid metabolism in adipose tissue. It is interesting that, depending on the type and abundance, short-chain fatty acids can stimulate the process of lipolysis as well as the processes of adipogenesis and lipogenesis. In the process of regulating lipolysis, the main role is played by the enzyme HSL (hormone sensitive lipase), while the key regulators of the process of adipo- and lipogenesis in adipose tissue are the transcriptional regulators PPARγ (eng. peroxisome proliferator-activated receptor γ), SREBP-1 (eng. sterol regulatory element binding protein-1) and ChREBP (eng. carbohydrate response element binding protein). Elucidation of the molecular mechanisms of action of short-chain fatty acids on adipose tissue cells, primarily on the processes of regulation of adipogenesis and lipid metabolism, can contribute to more successful prevention and treatment of obesity through changes in the composition of intestinal microbiota and its products that can be controlled by different dietary regimes.