Abstract
BackgroundIntervention strategies for obesity are global issues that require immediate attention. One approach is to exploit the growing consensus that beneficial gut microbiota could be of use in intervention regimes. Our objective was to determine the mechanism by which the probiotic bacteria Lactobacillus paracasei ssp paracasei F19 (F19) could alter fat storage. Angiopoietin-like 4 (ANGPTL4) is a circulating lipoprotein lipase (LPL) inhibitor that controls triglyceride deposition into adipocytes and has been reported to be regulated by gut microbes.Methodology/Principal FindingsA diet intervention study of mice fed high-fat chow supplemented with F19 was carried out to study potential mechanistic effects on fat storage. Mice given F19 displayed significantly less body fat, as assessed by magnetic resonance imaging, and a changed lipoprotein profile. Given that previous studies on fat storage have identified ANGPTL4 as an effector, we also investigated circulating levels of ANGPTL4, which proved to be higher in the F19-treated group. This increase, together with total body fat and triglyceride levels told a story of inhibited LPL action through ANGPTL4 leading to decreased fat storage. Co-culture experiments of colonic cell lines and F19 were set up in order to monitor any ensuing alterations in ANGPTL4 expression by qPCR. We observed that potentially secreted factors from F19 can induce ANGPTL4 gene expression, acting in part through the peroxisome proliferator activated receptors alpha and gamma. To prove validity of in vitro findings, germ-free mice were monocolonized with F19. Here we again found changes in serum triglycerides as well as ANGPTL4 in response to F19.Conclusions/SignificanceOur results provide an interesting mechanism whereby modifying ANGPTL4, a central player in fat storage regulation, through manipulating gut flora could be an important gateway upon which intervention trials of weight management can be based.
Highlights
Despite continuing efforts to educate the public on the link between being excessively overweight and developing chronic diseases, the prevalence of obesity continues to increase
Conclusions/Significance: Our results provide an interesting mechanism whereby modifying Angiopoietin-like 4 (ANGPTL4), a central player in fat storage regulation, through manipulating gut flora could be an important gateway upon which intervention trials of weight management can be based
ANGPTL4 is a downstream target gene of peroxisome proliferator activated receptors (PPAR), the agonists of which are widely used for the treatment of type 2 diabetes and dyslipidemia [4,5]
Summary
Despite continuing efforts to educate the public on the link between being excessively overweight and developing chronic diseases, the prevalence of obesity continues to increase (reviewed in [1]). This rapid increase and its significant health and economic burden have motivated a search for better prevention and treatment strategies. A critical event in the fasting response is its metabolic adaptations and the liberation of fatty acids from adipose tissue governed by numerous endocrine and cellular factors. Angiopoietin-like 4 (ANGPTL4) is a circulating lipoprotein lipase (LPL) inhibitor that controls triglyceride deposition into adipocytes and has been reported to be regulated by gut microbes
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