Pancreatic acinar cell-specific overexpression of group 1B phospholipase A(2) exacerbates diet-induced obesity and insulin resistance in mice

Department of Pathology, Metabolic Diseases Institute, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA.
International journal of obesity (2005) (Impact Factor: 5). 10/2010; 35(6):877-81. DOI: 10.1038/ijo.2010.215
Source: PubMed


Genome-wide association studies have identified significant association between polymorphisms of the Group 1B phospholipase A(2) (PLA2G1B) gene and central obesity in humans. Previous studies have shown that Pla2g1b inactivation decreases post-prandial lysophospholipid absorption, and as a consequence increases hepatic fatty acid oxidation and protects against diet-induced obesity and glucose intolerance in mice. The present study showed that transgenic mice with pancreatic acinar cell-specific overexpression of the human PLA2G1B gene gained significantly more weight and displayed elevated insulin resistance characteristics, such as impaired glucose tolerance, compared with wild-type (WT) mice, when challenged with a high-fat/carbohydrate diet. Pre- and post-prandial plasma β-hydroxybutyrate levels were also lower, indicative of decreased hepatic fatty acid oxidation, in the hypercaloric diet-fed PLA2G1B transgenic mice. These, along with earlier observations of Pla2g1b-null mice, document that Pla2g1b expression level is an important determinant of susceptibility to diet-induced obesity and diabetes, suggesting that the relationship between PLA2G1B polymorphisms and obesity may be due to differences in PLA2G1B expression levels between these individuals. The ability of pancreas-specific overexpression of PLA2G1B to promote obesity and glucose intolerance suggests that target phospholipase activity in the digestive tract with non-absorbable inhibitors should be considered as a therapeutic option for metabolic disease therapy.

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Available from: David G Kuhel, Mar 10, 2015
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    • "PLA 2 Family Group Gene Name Source MW (kDa) Catalytic Residues [Ca 2+ ] Pathologies cPLA 2 IVA to F PLA2G4A to F Human/murine 60–85 Ser/Asp mM N/A iPLA 2 VIA to F PLA2GVIA to F Human/murine 28–146 Ser/Asp None N/A PAF-AH VIIA & VIIB PLA2G7A, PLA2G7B Human/murine/ porcine/bovine 40–45 Ser/His/Asp None N/A VIIIA & VIIIB PLA2G8A, PLA2G8B Human $26 Ser/His/Asp N/A Ly-PLA 2 XV PLA2G15 Human $45 Ser/His/Asp None N/A AdPLA 2 XVI PLA2G16 Human Adipocyte $18 His/Cys None N/A sPLA 2 IA PLA2G1A Cobras and Kraits $14 His/Asp mM N/A IB PLA2G1B Human/porcine pancreas $14 Pancreatic acinar carcinoma [93] "
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