Mechanism of hypertriglyceridemia in CTP:phosphoethanolamine cytidylyltransferase-deficient mice.

Abstract

Phosphatidylethanolamine is an important inner-leaflet phospholipid, and CTP:phosphoethanolamine cytidylyltransferase-Pcyt2 acts as the main regulator of the de novo phosphatidylethanolamine synthesis from ethanolamine and diacylglycerol. Complete deletion of the mouse Pcyt2 gene is embryonic lethal, and the single-allele deficiency leads to development of the metabolic syndrome phenotype, including liver steatosis, hypertriglyceridemia, obesity, and insulin resistance. This study aimed to specifically elucidate the mechanisms of hypertriglyceridemia in Pcyt2 heterozygous mice (Pcyt2(+/-)). Evidence here shows that unlike 8 week-old mice, 32 week- and 42 week-old Pcyt2(+/-) mice experience increased VLDL secretion and liver microsomal triglyceride transfer protein activity. Older Pcyt2(+/-) mice also demonstrate increased levels of postprandial plasma TAGs, increased stimulation of genes responsible for intestinal lipid absorption, transport and chylomicron secretion, and dramatically elevated plasma Angptl4, apoB-100, and apoB-48 content. In addition, plasma HL and LPL activities and TAG clearance following a lipid challenge were significantly reduced in Pcyt2(+/-) mice relative to control littermates. Collectively, these results establish that the hypertriglyceridemia that accompanies Pcyt2 deficiency is the result of multiple metabolic adaptations, including elevated hepatic and intestinal lipoprotein secretion and stimulated expression and/or activity of genes involved in lipid absorption and transport and lipoprotein assembly, together with reduced plasma TAG clearance and utilization with peripheral tissues.

• Authors: Ratnesh Kumar Singh, Morgan D Fullerton, Donna Vine, Marica Bakovic
• Journal: Journal of lipid research (J Lipid Res) Vol. 53 Issue 9 Pg. 1811-22 (Sep 2012) ISSN: 1539-7262 [Electronic] United States
• PMID: 22764088 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiopoietin-Like Protein 4
• Angiopoietins
• Angptl4 protein, mouse
• Apolipoproteins B
• Carrier Proteins
• Chylomicrons
• Fatty Acids
• Triglycerides
• microsomal triglyceride transfer protein
• RNA Nucleotidyltransferases
• Ethanolamine-phosphate cytidylyltransferase
• Lipase
• Lipc protein, mouse
• Lipoprotein Lipase

Topics

• Angiopoietin-Like Protein 4
• Angiopoietins (genetics)
• Animals
• Apolipoproteins B (blood)
• Carrier Proteins (metabolism)
• Chylomicrons (biosynthesis, metabolism)
• Fatty Acids (metabolism)
• Gene Expression Regulation, Enzymologic
• Homeostasis
• Hypertriglyceridemia (blood, enzymology, metabolism)
• Intestinal Absorption (genetics)
• Intestinal Mucosa (metabolism)
• Lipase (blood)
• Lipoprotein Lipase (blood, genetics)
• Liver (metabolism)
• Mice
• Postprandial Period
• RNA Nucleotidyltransferases (deficiency)
• Triglycerides (blood, metabolism)