Management of Hypercholesterolemia Through Dietary ß-glucans–Insights From a Zebrafish Model

Adnan Hussain Gora,Prabhugouda Siriyappagouder,Jorge Dias,Saima Rehman,Pål Asgeir Olsvik,Jorge M O Fernandes,Ulrike Schmid-Staiger,Viswanath Kiron,Ioannis Vatsos,Konstantin Frick,Miguel Cardoso

doi:10.3389/fnut.2021.797452

Abstract

Consumption of lipid-rich foods can increase the blood cholesterol content. β-glucans have hypocholesterolemic effect. However, subtle changes in their molecular branching can influence bioactivity. Therefore, a comparative investigation of the cholesterol-lowering potential of two β-glucans with different branching patterns and a cholesterol-lowering drug, namely simvastatin was undertaken employing the zebrafish (Danio rerio) model of diet-induced hypercholesterolemia. Fish were allocated to 5 dietary treatments; a control group, a high cholesterol group, two β-glucan groups, and a simvastatin group. We investigated plasma total cholesterol, LDL and HDL cholesterol levels, histological changes in the tissues, and explored intestinal transcriptomic changes induced by the experimental diets. Dietary cholesterol likely caused the suppression of endogenous cholesterol biosynthesis, induced dysfunction of endoplasmic reticulum and mitochondria, and altered the histomorphology of the intestine. The two β-glucans and simvastatin significantly abated the rise in plasma cholesterol levels and restored the expression of specific genes to alleviate the endoplasmic reticulum-related effects induced by the dietary cholesterol. Furthermore, the distinct patterns of transcriptomic changes in the intestine elicited by the oat and microalga β-glucans impacted processes such as fatty acid metabolism, protein catabolic processes, and nuclear division. Oat and microalgal β-glucans also altered the pattern of lipid deposition in the liver. Our study provides insights into the effectiveness of different β-glucans to alleviate dysfunctions in lipid metabolism caused by dietary cholesterol.

Highlights

The drastic shift in the global food system has driven a new trend in consuming calorie-rich and highly processed foods [1]
We examined the effect of purified dietary cholesterol on different cholesterol species that are present in the plasma of adult zebrafish
We found a significant reduction of total cholesterol in the AG and oat glucan (OG) groups compared to the high cholesterol diet (HC) group (Figure 2A)

Summary

Introduction

The drastic shift in the global food system has driven a new trend in consuming calorie-rich and highly processed foods [1]. HDL performs cholesterol efflux from peripheral tissues to the liver, and the lipoprotein is known to possess antiinflammatory and antioxidative effects as well as LDL oxidation lowering ability [7]. The liver and intestine are the two principal organs that regulate the circulating lipoproteins and cholesterol homeostasis in the body, and specific receptors are known to facilitate metabolism linked to bile and dietary cholesterol [8, 9]. If the cholesterol content of the hepatocytes is high, LDL receptor activity is decreased [13], causing a reduction in the uptake of LDL by the hepatocytes. This in turn increases the amounts of LDL in circulation. Higher LDL cholesterol content in the blood is directly associated with lifestyle diseases like ischemic heart disease and stroke [3, 14]

Methods

Results

Conclusion