AGPAT2

The AGPAT2 gene provides instructions for making an enzyme that plays a critical role in the growth and development of adipocytes, which are the body's fat-storing cells.

The AGPAT2 enzyme is part of a chemical pathway that produces two important types of fats (lipids): glycerophospholipids and triacylglycerols. Glycerophospholipids are the major component of cell membranes throughout the body; they are also involved in chemical signaling within cells. Triacylglycerols (also known as triglycerides) are molecules in adipocytes that store fats for later conversion to energy.

The AGPAT2 enzyme is responsible for a particular chemical reaction in the production of these two types of lipids. Specifically, the enzyme helps convert a molecule called lysophosphatidic acid (LPA) to another molecule, phosphatidic acid (PA). Additional reactions convert phosphatidic acid to glycerophospholipids and triacylglycerols.

Berardinelli-Seip congenital lipodystrophy - caused by mutations in the AGPAT2 gene

At least 26 mutations in the AGPAT2 gene have been identified in people with Berardinelli-Seip congenital lipodystrophy type 1. These mutations alter the structure and function of the AGPAT2 enzyme.

Studies have shown that a defective AGPAT2 enzyme interferes with the normal development and function of adipocytes, which prevents the body from using and storing fats properly. Researchers propose that the abnormal AGPAT2 enzyme may reduce the production and storage of triacylglycerols in adipocytes, which would make these cells unable to store fats. The defective enzyme may also reduce the levels of glycerophospholipids in adipocytes, which would change the structure of the cell membrane and disrupt normal signaling within these cells. A lack of functional adipocytes leads to an almost total absence of body fat, which underlies most of the features of Berardinelli-Seip congenital lipodystrophy.