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.

Highlights

  • Angiopoietin-like protein 4 (ANGPTL4) is a lipoprotein lipase inhibitor that is involved in lipid metabolism and angiogenesis

  • ANGPTL4 concentration, blood lipid profile, insulin or glucose concentration did not change during the high-fat milk or the inulin intervention period, compared with the control period, nor did the diets have any effect on resting energy expenditure and lipid oxidation (Table 2)

  • Microbiota analyses showed only minor effects of the diets where inulin increased the relative abundance of bifidobacteria, compared with control, and milk increased the relative abundance of Roseburia, compared with inulin

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Summary

Introduction

Angiopoietin-like protein 4 (ANGPTL4) is a lipoprotein lipase inhibitor that is involved in lipid metabolism and angiogenesis. A short-term (3 d) human study observed an up-regulation of plasma ANGPTL4 in response to a high-fat diet (69 % energy (E%) as fat), a very low-energy diet (471 kcal/d; 1971 kJ/d) and fasting[6], which suggests that an increased concentration of NEFA in the bloodstream up-regulates expression of ANGPTL4. This up-regulation has been shown in vitro as expression of ANGPTL4 is up-regulated in response to exposure to fatty acids, including 16 : 0, 18 : 1n-9 and 20 : 4n-6 in cell studies[12,13]

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