ArticleCellular and molecular gastroenterology and hepatology2026
Cysteine 129 in Pla2g12b Is Critical for Intestinal and Hepatic Lipoprotein Secretion in Mice.
Article in Cellular and molecular gastroenterology and hepatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Dyslipidaemia and hepatic steatosis: mechanisms and implications for lipid-lowering therapy.Nature reviews. Cardiology · 2026Review
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9 authors.
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Abstract
BACKGROUND &
aimsLipoprotein assembly in the small intestine and liver is critical for the transport of dietary and endogenous lipids. Pla2g12b has recently been shown to play a role in lipoprotein assembly in mice livers and zebrafish larvae. Pla2g12b knockout and mutant (MUT) mice with the C129Y missense mutation have low plasma cholesterol levels. However, the role of Pla2g12b in the intestine and the reason why C129Y mutation decreases plasma lipids are unknown.
methodsBoth male and female 3-month-old chow fed Pla2g12b
resultsWe observed that Pla2g12b expression was the highest in the duodenum. Furthermore, male and female chow fed 3-month-old MUT mice and wildtype (WT) mice expressed similar amounts of Pla2g12b protein and several genes in lipid metabolism. Nonetheless, the MUT mice had significantly lower plasma triglyceride (TG), cholesterol, HDL-C, LDL-C, apoB48, and apoB100 levels than WT mice. Several mechanisms for lower plasma lipids and lipoproteins in MUT mice were investigated. C129Y mutation had no effect on the expression of Pla2g12b and several other proteins necessary for lipid transport. Therefore, the low plasma lipid levels in MUT mice were neither due to the absence of Pla2g12b protein nor due to reductions in critical proteins in lipid transport. Next, we addressed the role of Pla2g12b in hepatic lipid mobilization and intestinal lipid absorption. MUT livers exhibited normal TG synthesis, defective TG secretion, and enhanced fat accumulation. MUT mice also showed defective intestinal TG absorption, intracellular lipid accumulation, and elevated TG excretion in the feces.
conclusionsWe propose that C129 in Pla2g12b is critical for the assembly and secretion of lipoproteins by the liver and intestine.
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