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

Consumption of lipid-rich foods can increase the blood cholesterol content.
b-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 b-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 b-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 b-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 b-glucans impacted processes
such as fatty acid metabolism, protein catabolic processes, and nuclear division. Oat
and microalgal b-glucans also altered the pattern of lipid deposition in the liver. Our study
provides insights into the effectiveness of different b-glucans to alleviate dysfunctions in
lipid metabolism caused by dietary cholesterol.