Abstract
Background and ObjectivesIdentification of new targets for metabolic diseases treatment or prevention is required. In this context, FIAF/ANGPTL4 appears as a crucial regulator of energy homeostasis. Lactobacilli are often considered to display beneficial effect for their hosts, acting on different regulatory pathways. The aim of the present work was to study the effect of several lactobacilli strains on Fiaf gene expression in human intestinal epithelial cells (IECs) and on mice tissues to decipher the underlying mechanisms.Subjects and MethodsNineteen lactobacilli strains have been tested on HT–29 human intestinal epithelial cells for their ability to regulate Fiaf gene expression by RT-qPCR. In order to determine regulated pathways, we analysed the whole genome transcriptome of IECs. We then validated in vivo bacterial effects using C57BL/6 mono-colonized mice fed with normal chow.ResultsWe identified one strain (Lactobacillus rhamnosus CNCMI–4317) that modulated Fiaf expression in IECs. This regulation relied potentially on bacterial surface-exposed molecules and seemed to be PPAR-γ independent but PPAR-α dependent. Transcriptome functional analysis revealed that multiple pathways including cellular function and maintenance, lymphoid tissue structure and development, as well as lipid metabolism were regulated by this strain. The regulation of immune system and lipid and carbohydrate metabolism was also confirmed by overrepresentation of Gene Ontology terms analysis. In vivo, circulating FIAF protein was increased by the strain but this phenomenon was not correlated with modulation Fiaf expression in tissues (except a trend in distal small intestine).ConclusionWe showed that Lactobacillus rhamnosus CNCMI–4317 induced Fiaf expression in human IECs, and increased circulating FIAF protein level in mice. Moreover, this effect was accompanied by transcriptome modulation of several pathways including immune response and metabolism in vitro.
Highlights
Over the last decades, increased obesity is associated with increased metabolic syndromes characterized by type-2-diabetes (T2D), cardiovascular diseases (CVD) or low-grade inflammation
We identified one strain (Lactobacillus rhamnosus CNCMI–4317) that modulated Fiaf expression in intestinal epithelial cells (IECs)
In vivo, circulating FIAF protein was increased by the strain but this phenomenon was not correlated with modulation Fiaf expression in tissues
Summary
Over the last decades, increased obesity is associated with increased metabolic syndromes characterized by type-2-diabetes (T2D), cardiovascular diseases (CVD) or low-grade inflammation. Regarding the increased prevalence of these diseases, scientific interest has emerged in developing new therapeutic approaches. The recognition of FIAF (Fasting Induced Adipose Factor) protein as a central regulator of energy homeostasis emphasized it as a strong candidate in obesity-associated disorders treatment and/or prevention. FIAF known as ANGTPL4 (angiopoietin-like 4), is an adipokine expressed in several tissues including adipose tissue, liver, intestine and heart. With increasing studies on FIAF, it seems that its physiological effects are tissues dependent. FIAF inhibits lipoprotein lipase (LPL) and promotes lipolysis resulting in increased triglycerides (TGs) serum level and decreased free fatty acids (FA) and cholesterol uptake into different tissues [1, 2]. A direct interaction has been established, exact mechanism of LPL inhibition is still not fully elucidated [3,4,5]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
