Fatty acids, triglycerides, and glucose metabolism: recent insights from knockout mice

Cellular lipid metabolism plays an important role in modulating glucose metabolism. Recent models of mice with disruptions in genes involved in cellular fatty acid and triglyceride metabolism have provided insight into the long recognized but incompletely understood relationship between fatty acid metabolism and glucose metabolism.

Here we review findings from mice with deficiency in selected genes involved in the cellular uptake, storage, and hydrolysis of fatty acids. Our review is organized from the perspective of a fatty acid, as it makes its way from the circulation into the anabolic and then catabolic pathways in the cell. Although we focus primarily on the phenotypes of knockout mice, we also point out several transgenic models in which the overexpression phenotype provides complementary information.

The inactivation of enzymes in the anabolic process of fatty acid uptake and storage is more likely to enhance tissue glucose disposal or insulin secretion, whereas disruptions in the catabolic process tend to impair insulin action or secretion. These findings suggest that pharmacological inhibition of fatty acid uptake or storage may be an effective strategy for treating insulin resistance and diabetes.