Associations between hepatic miRNA expression, liver triacylglycerols and gut microbiota during metabolic adaptation to high-fat diet in mice

Abstract

Aims/hypothesis Despite the current pandemic of metabolic diseases, our understanding of the diverse nature of the development of metabolic alterations in people who eat a high-fat diet (HFD) is still poor. We recently demonstrated a cardiometabolic adaptation in mice fed an HFD, which was characterised by a specific gut and periodontal microbiota profile. Since the severity of hepatic disease is characterised by specific microRNA (miRNA) signatures and the gut microbiota is a key driver of both hepatic disease and miRNA expression, we analysed the expression of three hepatic miRNA and studied their correlation with hepatic triacylglycerol content and gut microbiota.Methods Two cohorts of C57BL/6 4-week-old wild-type (WT) male mice (n = 62 and n = 96) were fed an HFD for 3 months to provide a model of metabolic adaptation. Additionally 8-week-old C57BL/6 mice, either WT or of different genotypes, with diverse gut microbiota (ob/ob, Nod1, Cd14 knockout [Cd14KO] and Nod2) or without gut microbiota (axenic mice) were fed a normal chow diet. Following which, glycaemic index, body weight, blood glucose levels and hepatic triacylglycerol levels were measured. Gut (caecum) microbiota taxa were analysed by pyrosequencing. To analyse hepatic miRNA expression, real-time PCR was performed on total extracted miRNA samples. Data were analysed using two-way ANOVA followed by the Dunnett's post hoc test, or by the unpaired Student's t test. A cluster analysis and multivariate analyses were also performed. Results Our results demonstrated that the expression of miR-181a, miR-666 and miR-21 in primary murine hepatocytes is controlled by lipopolysaccharide in a dose-dependent manner. Of the gut microbiota, Firmicutes were positively correlated and Proteobacteria and Bacteroides acidifaciens were negatively correlated with liver triacylglycerol levels. Furthermore, the relative abundance of Firmicutes was negatively correlated with hepatic expression of miR-666 and miR-21. In contrast, the relative abundance of B. acidifaciens was positively correlated with miR-21. Conclusions/interpretation We propose the involvement of hepatic miRNA, liver triacylglycerols and gut microbiota as a new triad that underlies the molecular mechanisms by which gut microbiota governs hepatic pathophysiology during metabolic adaptation to HFD.

Dietary Exposure to the Environmental Chemical, PFOS on the Diversity of Gut Microbiota, Associated With the Development of Metabolic Syndrome

“…B. acidifaciens is one of the predominant bacterial species responsible for promoting IgA production in the large intestine and is a specific commensal bacterium associated with amelioration of metabolic disorders in mice ( Yanagibashi et al, 2013 ; Yang et al, 2017 ). The abundance of B. acidifaciens was found to be negatively correlated with liver TG levels in mice fed with a high-fat diet ( Blasco-Baque et al, 2017 ), which supports our data indicating negative correlation between the levels of hepatic and serum TG in PFOS-exposed mice. The family Dehalobacteriaceae showed reduced abundance only in the high-dose group, which was contributed by the decrease in Dehalobacterium .…”

Interactions between the MicroRNAs and Microbiota in Cancer Development: Roles and Therapeutic Opportunities

“…For instance, lung cancer microbiota is enriched in Proteobacteria and is more diverse in adenocarcinoma and squamous cell carcinoma, particularly in males and heavier smokers [91]. On the other hand, numerous miRNAs are differently expressed in lung disease [92,93], and miRNA-21 is overexpressed in lung cancer [94], and it is well known that numerous elements of the microbiota such as Bacteroides, Lactococcus lactis and Fusobacterium nucleatum are able to modify the expression of this miRNA [31,43,50].…”

“…Moreover, Firmicutes are negatively correlated with hepatic concentrations of miRNA-21 and miRNA-666, while B. acidifaciens is positively correlated with miR-21. Hepatic miRNAs, liver triacylglycerols and gut microbiota could be a novel triad that can explain the mechanism by which gut microbiota regulates hepatic pathophysiology [43].…”

Differences in Gut Microbiome Composition between Senior Orienteering Athletes and Community-Dwelling Older Adults

“…Parasutterella excrementihominis belongs to the class Betaproteobacteria (one of eight classes of Proteobacteria). The relative abundance of Parasutterella excrementihominis has previously been associated with different host health outcomes such as inflammatory bowel disease, irritable bowel syndrome, obesity, diabetes, and fatty liver disease [60][61][62][63]. Bilophila is a member of the hydrogen sulphide (H 2 S)-producing family Desulfovibrionaceae.…”