A randomised, controlled, crossover study of the effect of diet on angiopoietin-like protein 4 (ANGPTL4) through modification of the gut microbiome

Abstract

Angiopoietin-like protein 4 (ANGPTL4) is a lipoprotein lipase inhibitor that is involved in lipid metabolism and angiogenesis. Animal studies have suggested that the ANGPTL4 protein is modulated by the gut microbiota, possibly through increased concentrations of SCFA, such as C4, found in whole-fat milk or as a result of fermentation of inulin. This study investigated whether a standardised diet either high in fat content or supplemented with inulin powder would increase plasma ANGPTL4 in overweight men and whether this increase was mediated through a compositional change of the gut microbiota. The study had a crossover design with three arms, where participants were given a standardised isoenergetic diet supplemented with inulin powder, whole-fat milk or water (control). Plasma and urine samples were collected before and after each intervention period. Faecal samples and adipose tissue biopsies were collected after each intervention period. The study included twenty-one participants of whom eighteen completed the study. The dietary interventions did not change ANGPTL4 plasma concentration, nor was plasma ANGPTL4 associated with plasma lipids, TAG or NEFA concentration. The relative abundance of bifidobacteria following the inulin diet was higher, compared with the control diet. However, the changes in microbiota were not associated with plasma ANGPTL4 and the overall composition of the microbiota did not change between the dietary periods. Although weight was maintained throughout the dietary periods, weight was negatively associated with plasma ANGPTL4 concentration. In the adipose tissue, ANGPTL4 expression was correlated with leptin expression, but not with hypoxia-inducible factor 1α (HIF-1α) expression.

The Role of Gut Microbiota and Its Produced Metabolites in Obesity, Dyslipidemia, Adipocyte Dysfunction, and Its Interventions

“…In humans, few studies have investigated Angptl4 modulation by GM through SCFA or other metabolites. One study failed to illustrate associations between changes in the microbiota and Angptl4, did not find an influence of changes in diet on Angptl4 concentrations, and did not find a correlation between Angptl4 and plasma lipid levels [ 96 ]. However, this study investigated 18 participants, and larger studies evaluating the effect of GM or its metabolites including SCFAs on Angptl4 are therefore likely of added value.…”

A review of the multifunctionality of angiopoietin-like 4 in eye disease

“…Recent research also demonstrated that ANGPTL4 promotes bile acid (BA) absorption via the gut microbiota mechanism [ 59 ]. Later, Larsen and co-workers [ 60 ] pointed out that ANGPTL4 can not be effectively regulated by modifying the gut microbiota composition. Furthermore, E40K nucleotide polymorphisms of the ANGPTL4 gene decreased oligomer formation, which is correlated with decreased LPL inhibition activity and significantly lower triglyceride levels [ 17 ].…”

Pre-Weaning Inulin Supplementation Alters the Ileal Transcriptome in Pigs Regarding Lipid Metabolism

“…ANGPTL4 is a lipoprotein lipase inhibitor involved in both lipid metabolism and angiogenesis [27]. It is secreted by entero-endocrine cells and has been proposed as a mediator between gut microbiota and fat storage in adipose tissue [28], by inhibiting the circulating lipoprotein lipase that regulates the uptake of triglycerides in adipocytes [29].…”