Mice Lacking Phosphatidylinositol Transfer Protein-α Exhibit Spinocerebellar Degeneration, Intestinal and Hepatic Steatosis, and Hypoglycemia

• Published in: The Journal of biological chemistry Vol. 278; no. 35; p. 33501
• Main Authors: James G. Alb, Jr, Jorge D. Cortese, Scott E. Phillips, Roger L. Albin, Tim R. Nagy, Bruce A. Hamilton, Vytas A. Bankaitis
• Format: Journal Article
• Language: English
• Published: American Society for Biochemistry and Molecular Biology 29.08.2003
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M303591200

Phosphatidylinositol transfer proteins (PITPs) regulate the interface between lipid metabolism and cellular functions. We now report that ablation of PITPα function leads to aponecrotic spinocerebellar disease, hypoglycemia, and intestinal and hepatic steatosis in mice. The data indicate that hypoglycemia is in part associated with reduced proglucagon gene expression and glycogenolysis that result from pancreatic islet cell defects. The intestinal and hepatic steatosis results from the intracellular accumulation of neutral lipid and free fatty acid mass in these organs and suggests defective trafficking of triglycerides and diacylglycerols from the endoplasmic reticulum. We propose that deranged intestinal and hepatic lipid metabolism and defective proglucagon gene expression contribute to hypoglycemia in PITP α – / – mice, and that hypoglycemia is a significant contributing factor in the onset of spinocerebellar disease. Taken together, the data suggest an unanticipated role for PITPα in with glucose homeostasis and in mammalian endoplasmic reticulum functions that interface with transport of specific luminal lipid cargoes.