Group 1B phospholipase A2 deficiency protects against diet-induced hyperlipidemia in mice

Excessive absorption of products of dietary fat digestion leads to type 2 diabetes and other obesity-related disorders. Mice deficient in the group 1B phospholipase A2 (Pla2g1b), a gut digestive enzyme, are protected against diet-induced obesity and type 2 diabetes without displaying dietary lipid malabsorption. This study tested the hypothesis that inhibition of Pla2g1b protects against diet-induced hyperlipidemia. Results showed that the Pla2g1b −/− mice had decreased plasma triglyceride and cholesterol levels compared with Pla2g1b +/+ mice subsequent to feeding a high-fat, high-carbohydrate (hypercaloric) diet. These differences were evident before differences in body weight gains were observed. Injection of Poloxamer 407 to inhibit lipolysis revealed decreased VLDL production in Pla2g1b −/− mice. Supplementation with lysophosphatidylcholine, the product of Pla2g1b hydrolysis, restored VLDL production rates in Pla2g1b −/− mice and further elevated VLDL production in Pla2g1b +/+ mice. The Pla2g1b −/− mice also displayed decreased postprandial lipidemia compared with Pla2g1b +/+ mice. These results show that, in addition to dietary fatty acids, gut-derived lysophospholipids derived from Pla2g1b hydrolysis of dietary and biliary phospholipids also promote hepatic VLDL production. Thus, the inhibition of lysophospholipid absorption via Pla2g1b inactivation may prove beneficial against diet-induced hyperlipidemia in addition to the protection against obesity and diabetes. Excessive absorption of products of dietary fat digestion leads to type 2 diabetes and other obesity-related disorders. Mice deficient in the group 1B phospholipase A2 (Pla2g1b), a gut digestive enzyme, are protected against diet-induced obesity and type 2 diabetes without displaying dietary lipid malabsorption. This study tested the hypothesis that inhibition of Pla2g1b protects against diet-induced hyperlipidemia. Results showed that the Pla2g1b −/− mice had decreased plasma triglyceride and cholesterol levels compared with Pla2g1b +/+ mice subsequent to feeding a high-fat, high-carbohydrate (hypercaloric) diet. These differences were evident before differences in body weight gains were observed. Injection of Poloxamer 407 to inhibit lipolysis revealed decreased VLDL production in Pla2g1b −/− mice. Supplementation with lysophosphatidylcholine, the product of Pla2g1b hydrolysis, restored VLDL production rates in Pla2g1b −/− mice and further elevated VLDL production in Pla2g1b +/+ mice. The Pla2g1b −/− mice also displayed decreased postprandial lipidemia compared with Pla2g1b +/+ mice. These results show that, in addition to dietary fatty acids, gut-derived lysophospholipids derived from Pla2g1b hydrolysis of dietary and biliary phospholipids also promote hepatic VLDL production. Thus, the inhibition of lysophospholipid absorption via Pla2g1b inactivation may prove beneficial against diet-induced hyperlipidemia in addition to the protection against obesity and diabetes. Obesity and diabetes-related disorders, including atherosclerosis and coronary artery disease, are rapidly reaching pandemic levels in industrialized countries, due at least in part to increasing consumption of high-fat diets in the general population (1Moller D.E. Kaufman K.D. Metabolic syndrome: a clinical and molecular perspective.Annu. Rev. Med. 2005; 56: 45-62Crossref PubMed Scopus (505) Google Scholar, 2Després J.P. Lemieux I. 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The lipid emulsions are hydrolyzed by pancreas-secreted lipolytic enzymes into fatty acids, monoacylglycerol, cholesterol, and lysophospholipids prior to the absorption of these lipid nutrients by the enterocytes (4Carey M.C. Small D.M. Bliss C.M. Lipid digestion and absorption.Annu. Rev. Physiol. 1983; 45: 651-677Crossref PubMed Scopus (639) Google Scholar, 5Hui D.Y. Howles P.N. Molecular mechanisms of cholesterol absorption and transport.Semin. Cell Dev. Biol. 2005; 16: 183-192Crossref PubMed Scopus (91) Google Scholar, 6Mansbach C.M. Siddiqi S.A. The biogenesis of chylomicrons.Annu. Rev. Physiol. 2010; 72: 315-333Crossref PubMed Scopus (144) Google Scholar). The lipid nutrients in the enterocytes are repackaged and then secreted into plasma circulation as triglyceride-rich lipoproteins (6Mansbach C.M. Siddiqi S.A. The biogenesis of chylomicrons.Annu. Rev. Physiol. 2010; 72: 315-333Crossref PubMed Scopus (144) Google Scholar). These chylomicrons, which are secreted by the intestine, supply lipid nutrients as an energy source to peripheral tissues, and excess fat is deposited in adipose tissues for storage as energy reserve (7Gesta S. Tseng Y-H. Kahn C.R. Developmental origin of fat: tracking obesity to its source.Cell. 2007; 131: 242-256Abstract Full Text Full Text PDF PubMed Scopus (1094) Google Scholar). The intestinal-derived chylomicrons and their remnants also transport dietary lipids to the liver, where they are reutilized for VLDL synthesis and further dissipation of the lipid nutrients to extrahepatic tissues (8Mahley R.W. Hussain M.M. Chylomicron and chylomicron remnant catabolism.Curr. Opin. Lipidol. 1991; 2: 170-176Crossref Scopus (105) Google Scholar). Fatty acids stored in adipose tissues as triglycerides can also be liberated from the storage pool and transported to the liver (9Iozzo P. Bucci M. Roivainen A. Nagren K. Jarvisalo M.J. Kiss J. Guiducci L. Fielding B. Naum A.G. 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Obesity and obesity-related metabolic complications ensue when dietary fat intake exceeds the energy requirement of each tissue. The excess fat stored in adipose tissues increases adiposity and promotes inflammation (13Hotamisligil G.S. Shargill N.S. Spiegelman B.M. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance.Science. 1993; 259: 87-91Crossref PubMed Scopus (6147) Google Scholar, 14Weisberg S.P. McCann D. Desai M. Rosenbaum M. Leibel R.L. Ferrante Jr., A.W. Obesity is associated with macrophage accumulation in adipose tissue.J. Clin. Invest. 2003; 112: 1796-1808Crossref PubMed Scopus (7473) Google Scholar). Excess fat uptake into skeletal muscle causes insulin resistance, and excessive fat deposited in the heart leads to lipotoxicity and cardiomyopathy (15Olefsky J.M. Glass C.K. Macrophages, inflammation, and insulin resistance.Annu. Rev. Physiol. 2010; 72: 219-246Crossref PubMed Scopus (1990) Google Scholar, 16Unger R.H. Minireview: weapons of lean body mass destruction: the role of ectopic lipids in the metabolic syndrome.Endocrinology. 2003; 144: 5159-5165Crossref PubMed Scopus (568) Google Scholar). Lipotoxicity of pancreatic islet cells due to excess fat uptake also reduces insulin secretion, resulting in robust hyperglycemia (16Unger R.H. Minireview: weapons of lean body mass destruction: the role of ectopic lipids in the metabolic syndrome.Endocrinology. 2003; 144: 5159-5165Crossref PubMed Scopus (568) Google Scholar). Recent genome-wide association studies have identified significant association (P < 0.01) between polymorphisms of the group 1B phospholipase A2 (PLA2G1B) gene PLA2G1B with central adiposity in humans (17Pérusse L. Rice T. Chagnon Y.C. Despres J-P. Lemieux S. Roy S. Lacaille M. Ho-Kim M-A. Chagnon M. Province M.A. et al.A genome-wide scan for abdominal fat assessed by computed tomography in the Quebec family study.Diabetes. 2001; 50: 614-621Crossref PubMed Scopus (129) Google Scholar, 18Chagnon Y.C. Merette C. Bouchard R.H. Emond C. Roy M.A. Maziade M. A genome wide linkage study of obesity as secondary effect of antipsychotics in multigenerational families of eastern Quebec affected by psychoses.Mol. Psychiatry. 2004; 9: 1067-1074Crossref PubMed Scopus (63) Google Scholar, 19Wilson S.G. Adam G. Langdown M. Reneland R. Braun A. Andrew T. Surdulescu G.L. Norberg M. Dudbridge F. Reed P.W. et al.Linkage and potential association of obesity-related phenotypes with two genes on chromosome 12q24 in a female dizygous twin cohort.Eur. J. Hum. Genet. 2006; 14: 340-348Crossref PubMed Scopus (52) Google Scholar). Previous studies from our laboratory have shown that Pla2g1b inactivation is protective against diet-induced obesity and hyperglycemia in mice (20Huggins K.W. Boileau A.C. Hui D.Y. Protection against diet-induced obesity and obesity-related insulin resistance in Group 1B PLA2-deficient mice.Am. J. Physiol. Endocrinol. Metab. 2002; 283: E994-E1001Crossref PubMed Scopus (103) Google Scholar, 21Hui D.Y. Cope M.J. Labonté E.D. Chang H-T. Shao J. Goka E. Abousalham A. Charmot D. Buysse J. The phospholipase A2 inhibitor methyl indoxam suppresses diet-induced obesity and glucose intolerance in mice.Br. J. Pharmacol. 2009; 157: 1263-1269Crossref PubMed Scopus (39) Google Scholar), suggesting that Pla2g1b to these diet-induced metabolic disorders. The Pla2g1b −/− mice are to diet-induced obesity due to their to elevated energy via increased hepatic fatty acid when a E.D. Hui D.Y. lysophospholipid suppresses hepatic fatty acid the molecular between group 1B phospholipase A2 and diet-induced J. 2010; PubMed Scopus Google Scholar). The elevated fatty acid in the liver of Pla2g1b −/− mice also reduces dietary fat to other tissues, increasing their on glucose as a source and resulting in protection against diet-induced glucose intolerance and hyperglycemia E.D. K.W. Hui D.Y. Group 1B phospholipase lysophospholipid absorption to postprandial 2006; PubMed Scopus Google Scholar). The group 1B phospholipase A2 is a in the and secreted into the intestinal lumen in to feeding Hui D.Y. Molecular and expression of the pancreatic phospholipase A2 PubMed Scopus Google Scholar). The of PLA2G1B is to phospholipids into fatty acids and lysophospholipids prior to intestinal absorption of other enzymes in the intestinal lumen can for digestion in the of Pla2g1b in mice Boileau A.C. S. K.W. P. Hui D.Y. digestion is for cholesterol absorption in pancreatic phospholipase A2 deficient 2001; Full Text Full Text PDF PubMed Scopus Google Scholar), they lysophospholipids to the the digestive E.D. K.W. Hui D.Y. Group 1B phospholipase lysophospholipid absorption to postprandial 2006; PubMed Scopus Google Scholar). lysophospholipid levels in mice deficient in Pla2g1b −/− the metabolic of obesity and diabetes resistance in these as elevated hepatic fatty acid and glucose in Pla2g1b −/− mice can be with E.D. Hui D.Y. lysophospholipid suppresses hepatic fatty acid the molecular between group 1B phospholipase A2 and diet-induced J. 2010; PubMed Scopus Google Scholar, E.D. K.W. Hui D.Y. Group 1B phospholipase lysophospholipid absorption to postprandial 2006; PubMed Scopus Google Scholar). the of and Pla2g1b inactivation glucose and had Pla2g1b inactivation also plasma lipid in to feeding The of hepatic fatty acid in Pla2g1b −/− mice their lipid in to This study to plasma lipid hepatic lipoprotein and postprandial triglyceride-rich lipoprotein between Pla2g1b +/+ and Pla2g1b −/− mice in to high-fat, high-carbohydrate feeding of weight The Pla2g1b −/− mice were by in cells and with mice to Pla2g1b −/− mice in E.D. K.W. Hui D.Y. Group 1B phospholipase lysophospholipid absorption to postprandial 2006; PubMed Scopus Google Scholar, Boileau A.C. S. K.W. P. Hui D.Y. digestion is for cholesterol absorption in pancreatic phospholipase A2 deficient 2001; Full Text Full Text PDF PubMed Scopus Google Scholar). Mice from Pla2g1b +/+ and Pla2g1b −/− were used to Pla2g1b +/+ and Pla2g1b −/− mice for were in a and with with to and mice were used for were or a which of fat from and at of for the as for each and were by the and at the of were from mice through the or via into by and cholesterol levels were measured from plasma in and Lipid lipoproteins by of plasma to on two as C. of plasma lipoprotein PubMed Scopus Google Scholar). for triglyceride and cholesterol were for at into the were to plasma lipid levels at The mice were then an of Poloxamer 407 at a of body weight to inhibit each of a shown to levels in Pla2g1b −/− mice to in Pla2g1b +/+ mice E.D. Hui D.Y. lysophospholipid suppresses hepatic fatty acid the molecular between group 1B phospholipase A2 and diet-induced J. 2010; PubMed Scopus Google Scholar, E.D. K.W. Hui D.Y. Group 1B phospholipase lysophospholipid absorption to postprandial 2006; PubMed Scopus Google Scholar), prior to blood were for plasma triglyceride to hepatic VLDL production rates hepatic triglyceride production in of 407 with Lipid 2005; Full Text Full Text PDF PubMed Scopus Google Scholar). the by and levels were measured by an of as to potential of as for VLDL mice were on for The were then and blood were to plasma lipid an of and blood were for plasma triglyceride by and results are as of an used of < were significant differences between a with < used to with results (20Huggins K.W. Boileau A.C. Hui D.Y. Protection against diet-induced obesity and obesity-related insulin resistance in Group 1B PLA2-deficient mice.Am. J. Physiol. Endocrinol. Metab. 2002; 283: E994-E1001Crossref PubMed Scopus (103) Google Scholar), Pla2g1b +/+ and Pla2g1b −/− mice displayed body when diet. the were with a high significant body weight in the Pla2g1b +/+ mice in a the Pla2g1b −/− mice were to body weight with in body weight compared with the in Pla2g1b +/+ mice of feeding the plasma triglyceride levels were between Pla2g1b +/+ and Pla2g1b −/− mice. the Pla2g1b +/+ mice showed of plasma triglyceride levels a plasma triglyceride levels in the Pla2g1b −/− mice and were in Pla2g1b +/+ mice Thus, feeding the for plasma triglyceride levels were in Pla2g1b −/− mice compared with the Pla2g1b +/+ mice. The Pla2g1b −/− mice also displayed plasma cholesterol levels compared with Pla2g1b +/+ dietary the Pla2g1b +/+ mice a on the as plasma cholesterol levels in the Pla2g1b −/− mice were to dietary with 2 and before and feeding the Thus, at the of the plasma cholesterol in Pla2g1b −/− mice compared with the Pla2g1b +/+ mice. of plasma from mice showed that in VLDL for the plasma triglyceride levels between Pla2g1b +/+ and Pla2g1b −/− mice. the Pla2g1b −/− mice also elevated plasma levels which are in mice high-fat feeding T. K. A. fat increases high density lipoprotein levels by increasing the transport rates and the rates of cholesteryl ester and Clin. Invest. 1993; PubMed Scopus Google Scholar). The the differences in plasma lipid levels between Pla2g1b +/+ and Pla2g1b −/− mice by hepatic VLDL production rates in these and dietary these mice were for to of triglycerides and then with to inhibit lipolysis of VLDL secreted by the were at and triglyceride levels were measured hepatic triglyceride production in of 407 with Lipid 2005; Full Text Full Text PDF PubMed Scopus Google Scholar). the were on a plasma triglyceride levels were between Pla2g1b +/+ and Pla2g1b −/− mice before and of in plasma triglyceride levels revealed significant in hepatic VLDL production rates between Pla2g1b +/+ mice and Pla2g1b +/+ mice also revealed in the of triglyceride secreted by Pla2g1b +/+ and Pla2g1b −/− mice significant differences in hepatic VLDL production were between Pla2g1b +/+ and Pla2g1b −/− mice feeding the the for two increased hepatic VLDL production rates in Pla2g1b +/+ mice to the hepatic VLDL production rates decreased in Pla2g1b −/− mice to the of the in the plasma of Pla2g1b +/+ mice compared with that in Pla2g1b −/− mice These differences in of hepatic VLDL production rates between Pla2g1b +/+ and Pla2g1b −/− mice were prior to in their body The differences in VLDL production of when differences in body weight gains were also observed. the of VLDL secretion a and VLDL production rates were in Pla2g1b +/+ mice compared with in Pla2g1b −/− mice that VLDL production a 2 in the Pla2g1b −/− mice. Previous in our laboratory shown that Pla2g1b −/− mice on have plasma levels of the product of compared with Pla2g1b +/+ mice on E.D. Hui D.Y. lysophospholipid suppresses hepatic fatty acid the molecular between group 1B phospholipase A2 and diet-induced J. 2010; PubMed Scopus Google Scholar). of plasma lysophospholipid in Pla2g1b −/− mice to that in Pla2g1b +/+ mice by of to the protective of Pla2g1b inactivation against glucose intolerance and postprandial hyperglycemia E.D. Hui D.Y. lysophospholipid suppresses hepatic fatty acid the molecular between group 1B phospholipase A2 and diet-induced J. 2010; PubMed Scopus Google Scholar). in the of to Pla2g1b −/− mice prior to also the of the VLDL production results showed that also increased the and of VLDL accumulation to levels in Pla2g1b +/+ which were that in Pla2g1b −/− mice without Injection of also increased levels in Pla2g1b +/+ mice to levels in mice without these results that promotes hepatic VLDL production and that the differences in plasma lipoprotein levels and VLDL production between Pla2g1b +/+ and Pla2g1b −/− mice are due to absorption and transport of lysophospholipids in the of the of into mice prior to and plasma to as for VLDL of the in plasma to be associated with VLDL in Pla2g1b +/+ and Pla2g1b −/− mice the lipoprotein associated The of from into VLDL due to association of the with in of with plasma showed that of the associated with and of the associated with the in VLDL in the triglyceride that the used as for VLDL lipid with in the VLDL of Pla2g1b +/+ mice compared with Pla2g1b −/− mice of plasma levels by between Pla2g1b +/+ and Pla2g1b −/− mice that the of particles secreted by the Thus, increases the production of VLDL particles with triglyceride of increasing the of lipoproteins secreted by the lipid levels are by lipoprotein synthesis and were to potential differences in triglyceride-rich lipoprotein between Pla2g1b +/+ and Pla2g1b −/− mice. these the mice were and then a of by triglyceride levels were at without Results showed plasma triglyceride levels between Pla2g1b +/+ and Pla2g1b −/− mice at and lipid plasma triglyceride levels were in Pla2g1b −/− mice compared with Pla2g1b +/+ mice lipid feeding plasma triglyceride levels to their levels in Pla2g1b −/− mice lipid plasma triglyceride levels in the Pla2g1b +/+ mice elevated compared with the the study of the revealed a in postprandial lipidemia in the Pla2g1b −/− mice compared with Pla2g1b +/+ mice Pla2g1b +/+ and Pla2g1b −/− mice are in lipid absorption (20Huggins K.W. Boileau A.C. Hui D.Y. Protection against diet-induced obesity and obesity-related insulin resistance in Group 1B PLA2-deficient mice.Am. J. Physiol. Endocrinol. Metab. 2002; 283: E994-E1001Crossref PubMed Scopus (103) Google Scholar, Boileau A.C. S. K.W. P. Hui D.Y. digestion is for cholesterol absorption in pancreatic phospholipase A2 deficient 2001; Full Text Full Text PDF PubMed Scopus Google Scholar), the postprandial triglyceride levels in Pla2g1b −/− mice their of triglyceride-rich lipoproteins compared with Pla2g1b +/+ mice. Thus, the significant differences in plasma triglyceride and cholesterol levels between Pla2g1b +/+ and Pla2g1b −/− mice were due to hepatic production as as increased of triglyceride-rich lipoproteins in the Pla2g1b −/− mice. This study showed that inactivation of the intestinal digestive Pla2g1b protects mice against elevated plasma triglyceride and cholesterol levels by a (hypercaloric) diet. The protection is of is a direct of hepatic VLDL production and increased triglyceride-rich lipoprotein in Pla2g1b −/− mice. This is by in hepatic VLDL production in Pla2g1b −/− mice compared with Pla2g1b +/+ mice prior to differences in body weight The group 1B phospholipase A2 phospholipids in the intestinal lumen to lipid absorption through the (4Carey M.C. Small D.M. Bliss C.M. Lipid digestion and absorption.Annu. Rev. Physiol. 1983; 45: 651-677Crossref PubMed Scopus (639) Google Scholar). The products of are nonesterified fatty acids and The in hepatic VLDL production between Pla2g1b +/+ and Pla2g1b −/− mice be to differences in nonesterified fatty acid absorption other in the digestive can for the of Pla2g1b in digestion in fat absorption in Pla2g1b −/− mice Boileau A.C. S. K.W. P. Hui D.Y. digestion is for cholesterol absorption in pancreatic phospholipase A2 deficient 2001; Full Text Full Text PDF PubMed Scopus Google Scholar), The in products in hydrolysis is that which are rapidly and transported to the liver through the E.D. K.W. Hui D.Y. Group 1B phospholipase lysophospholipid absorption to postprandial 2006; PubMed Scopus Google Scholar, P. M. T. of in of and atherosclerosis in Lipid Full Text PDF PubMed Google Scholar), are in the Pla2g1b −/− mice E.D. K.W. Hui D.Y. Group 1B phospholipase lysophospholipid absorption to postprandial 2006; PubMed Scopus Google Scholar). Results of the study show is a direct for the of reduces synthesis VLDL production can be restored by Thus, these results that absorption of in addition to fatty acids, also an role in hepatic VLDL production. The of lysophospholipid absorption with VLDL synthesis is Previous studies that hepatic secretion via of J. M. J. G. A. C. G. J. C. reduces and may secretion in human PubMed Scopus Google Scholar). the study showed in secretion between Pla2g1b +/+ and Pla2g1b −/− lysophospholipids may to hepatic VLDL production through other Previous in that can be to in hepatocytes, the for VLDL synthesis Z. D.E. metabolism and lipoprotein secretion by deficient in J. PubMed Scopus Google Scholar). also inhibit fatty acid in the liver E.D. Hui D.Y. lysophospholipid suppresses hepatic fatty acid the molecular between group 1B phospholipase A2 and diet-induced J. 2010; PubMed Scopus Google Scholar), increasing for may also to promote triglyceride and synthesis in D. G.F. of hepatic lipoprotein the of J. PubMed Scopus Google Scholar), of and VLDL secretion Z. J. A. Hussain M.M. increases secretion by lipid synthesis and its in PubMed Scopus Google Scholar). in are with the in that levels of VLDL synthesis and results showed that VLDL secretion between Pla2g1b +/+ and Pla2g1b −/− mice the of lipolysis The differences were due to VLDL production by Pla2g1b −/− mice at VLDL production in Pla2g1b +/+ mice at a The of to the Pla2g1b −/− mice restored VLDL production to levels as that in Pla2g1b +/+ mice The to the as lipid for VLDL and of further increased VLDL production in Pla2g1b +/+ mice. studies showed that the phospholipase A2 in the liver is for VLDL and secretion K. Z. Z. The of very low density lipoproteins in cells is by phospholipase A2 Biol. Full Text Full Text PDF PubMed Scopus Google Scholar), the study revealed that of lysophospholipid absorption via Pla2g1b gene inactivation is also in VLDL addition to VLDL secretion, Pla2g1b −/− mice also displayed of triglyceride-rich lipoproteins compared with Pla2g1b +/+ mice. Typically, triglyceride-rich lipoprotein via lipoprotein hydrolysis of the triglycerides to nonesterified fatty acids, which are then by extrahepatic tissues as nutrients or stored in adipose tissues as energy and via uptake of remnant the the in triglyceride-rich lipoprotein between Pla2g1b +/+ and Pla2g1b −/− mice a in lipoprotein between these is lipoprotein in adipose tissues and to fat uptake from triglyceride-rich lipoproteins are to promote obesity and insulin resistance, H. R.H. from gene to J. Physiol. Endocrinol. Metab. 2009; PubMed Scopus Google Scholar, K.W. of plasma triglyceride metabolism on lipid storage in adipose studies 2009; PubMed Scopus Google Scholar). the Pla2g1b −/− mice are to diet-induced obesity and glucose intolerance (20Huggins K.W. Boileau A.C. Hui D.Y. Protection against diet-induced obesity and obesity-related insulin resistance in Group 1B PLA2-deficient mice.Am. J. Physiol. Endocrinol. Metab. 2002; 283: E994-E1001Crossref PubMed Scopus (103) Google Scholar, E.D. K.W. Hui D.Y. Group 1B phospholipase lysophospholipid absorption to postprandial 2006; PubMed Scopus Google Scholar). the in hepatic fatty acid E.D. Hui D.Y. lysophospholipid suppresses hepatic fatty acid the molecular between group 1B phospholipase A2 and diet-induced J. 2010; PubMed Scopus Google and plasma lipid levels in Pla2g1b −/− mice that these are to diet-induced of expression in the Thus, the plasma of triglyceride-rich lipoproteins in Pla2g1b −/− mice is due to increased by the these results that Pla2g1b inactivation reduces diet-induced hyperlipidemia by VLDL production and the of triglyceride-rich inhibition of phospholipase A2 in the digestive may be to diet-induced hyperlipidemia in addition to the beneficial on obesity and diabetes D.Y. Cope M.J. Labonté E.D. Chang H-T. Shao J. Goka E. Abousalham A. Charmot D. Buysse J. The phospholipase A2 inhibitor methyl indoxam suppresses diet-induced obesity and glucose intolerance in mice.Br. J. Pharmacol. 2009; 157: 1263-1269Crossref PubMed Scopus (39) Google Scholar). Results of the study also showed plasma levels in Pla2g1b −/− mice compared with Pla2g1b +/+ mice. these results may an effect of Pla2g1b that Pla2g1b inactivation as levels were between Pla2g1b −/− mice and Pla2g1b +/+ and Pla2g1b −/− mice. The Pla2g1b −/− mice were to the in levels feeding of a suggesting that these were the increased supply of dietary lipids with lipid metabolism and glucose metabolism E.D. K.W. Hui D.Y. Group 1B phospholipase lysophospholipid absorption to postprandial 2006; PubMed Scopus Google to in the dietary lipids were in the liver and to the metabolism in Pla2g1b −/− mice E.D. Hui D.Y. lysophospholipid suppresses hepatic fatty acid the molecular between group 1B phospholipase A2 and diet-induced J. 2010; PubMed Scopus Google Scholar). The of Pla2g1b inactivation to the synthesis of the lipoprotein of the levels direct clinical for of plasma lipoprotein in the 407 group 1B phospholipase A2

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