Metabolic

The shortage of ANGPTL4 protein reduces ldl cholesterol and irritation

Atherosclerotic plaques from mice without ANGPTL4 in adipose tissue (bottom) are smaller and show less lipid accumulation (red) than in mice with ANGPTL4 (top).

Diet-related diabetes, obesity and heart disease are the leading causes of death worldwide. In their search for novel therapies for these related chronic diseases, Yale researchers examined a protein called ANGPTL4. The protein plays an essential role in regulating the metabolism of lipoproteins that carry fat and lipids in the blood and has been linked to an increased risk of heart disease in humans.

The senior authors Carlos Fernandez-Hernando and Yajaira Suárez and their colleagues had previously described the function of ANGPTL4 in immune cells, where it regulates lipid accumulation in the arteries and the development of atherosclerosis (hardened arteries). In order to understand the contribution of this protein to the control of lipid and glucose balance throughout the body, the research team created a novel mouse model in this follow-up study without ANGPTL4 in fat, where it is normally found in large quantities. They found that the mice with no ANGPTL4 in fat had improved sugar and lipid metabolism. These effects were observed not only in adipose tissue, but also in liver and muscle tissue.

In addition, in mice deficient in ANGPTL4, the researchers found reductions in cholesterol and inflammation, which decreased the formation of fats in arteries that can lead to heart disease. These results suggest that therapy that specifically targets the protein in adipose tissue can not only improve metabolism but also serve as a strategy for treating cardiovascular disease, the researchers said.

Binod Aryal and Abhishek Singh, the study’s first authors, plan to further investigate the protein in other metabolic tissues, including brown fat. Read the full article in JCI Insight.

Publication: Binod Aryal et al., “The absence of ANGPTL4 in adipose tissue improves glucose tolerance and weakens atherogenesis,” JCI Insight, 2018; doi: 10.1172 / jci.insight.97918

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