Cellular calcium levels may influence cholesterol production, study suggests

Calcium levels within cells may play an important role in controlling cholesterol production, according to recent research using roundworms.

The study, which appears in Scientific Reports, was a collaboration between the University of Alberta; McGill University, Quebec; and Hanyang University, Seoul.

Following an unexpected finding that low levels of a calcium binding protein - calreticulin, caused extreme rises in cholesterol levels in mice, the research team replicated the findings using roundworms - Caenorhabditis elegans (C.elegans).

The researchers discovered that when cellular levels of calcium in the worms became depleted - following calreticulin deficiency, the worms were unable to detect that adequate cholesterol was already present. Consequently, they continued to produce additional amounts of the lipid, leading to a large increase in blood cholesterol level.

"There is a mechanism inside the cell that senses when there is not enough cholesterol present and turns on the machinery to make more,"commented lead researcher Professor Marek Michalak, from the University of Alberta.  

"What we found is that a lack of calcium can hide cholesterol from this machinery. If you lose calcium, your synthetic machinery thinks there's no cholesterol and it starts making more even if there is already enough."

Cholesterol management implications

High blood cholesterol is a known risk factor for developing heart disease. Therefore, the discovery that cellular levels of calcium may be involved in regulating the production of cholesterol may facilitate new methods of controlling blood lipid levels.

“Factors that affect blood cholesterol concentration have been studied for a long time," said Professor Luis Agellon, from McGill University School of Human Nutrition.

"The general belief was that cholesterol controlled its own synthesis inside of cells, and then we discovered in our labs that calcium can control that function too. Finding this link potentially opens a door to developing new ways of controlling cholesterol metabolism," he added.

The researchers stressed the need for further work to clarify exactly how calcium and cholesterol communicate within the cell; and to replicate the effect in humans.  

Source: Scientific Reports

Volume 7, article number 5941. Published online, doi: 10.1038/s41598-017-05734-x

“Loss of Calreticulin Uncovers a Critical Role for Calcium in Regulating Cellular Lipid Homeostasis”

Authors:  Wen-An Wang, Wen-Xin Liu, et al