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

Hollie, Norris I.; Hui, David Y.

doi:10.1194/jlr.m019463

Cited by 40 publications

(38 citation statements)

References 36 publications

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“…The in vitro data collected in this study has direct physiological relevance, adding mechanistic information to our previous observations that PLA2G1B-mediated phospholipid digestion in the intestinal lumen after meal consumption contributes LPC to the liver to inhibit fatty acid oxidation and promote triglyceride synthesis for storage and/or VLDL secretion [8-10]. Herein we showed that meal-induced repression of fatty acid oxidation is likely caused by LPC-mediated suppression of mitochondrial function, thereby partitioning fatty acids absorbed from the meal to intracellular sites for triglyceride biosynthesis.…”

Section: Discussionmentioning

confidence: 63%

“…Systemic supplementation of LPC prior to oral lipid load decreases hepatic fatty acid oxidation to levels similar to those observed in Pla2g1b +/+ mice, as well as cause stimulation of triglyceride production in fasting Pla2g1b −/− and Pla2g1b +/+ mice [9, 10]. These observations suggest a direct and acute effect of LPC on hepatocytes and that Pla2g1b-mediated LPC absorption may play a role in postprandial partitioning of dietary fatty acids to triglyceride (TG) production instead of β-oxidation.…”

Section: Introductionmentioning

confidence: 99%

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Micromolar changes in lysophosphatidylcholine concentration cause minor effects on mitochondrial permeability but major alterations in function

Hollie

Cash

Matlib

et al. 2014

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Mice deficient in group 1b phospholipase A2 have decreased plasma lysophosphatidylcholine and increased hepatic oxidation that is inhibited by intraperitoneal lysophosphatidylcholine injection. This study sought to identify a mechanism for lysophosphatidylcholine-mediated inhibition of hepatic oxidative function. Results showed that in vitro incubation of isolated mitochondria with 40-200 μM lysophosphatidylcholine caused cyclosporine A-resistant swelling in a concentration-dependent manner. However, when mitochondria were challenged with 220 μM CaCl2, cyclosporine A protected against permeability transition induced by 40 μM, but not 80 μM lysophosphatidylcholine. Incubation with 40-120 μM lysophosphatidylcholine also increased mitochondrial permeability to 75 μM CaCl2 in a concentration-dependent manner. Interestingly, despite incubation with 80 μM lysophosphatidylcholine, the mitochondrial membrane potential was steady in the presence of succinate, and oxidation rates and respiratory controls indices were similar to controls in the presence of succinate, glutamate/malate, and palmitoyl-carnitine. However, mitochondrial oxidation rates were inhibited by 30-50% at 100 μM lysophosphatidylcholine. Finally, while 40 μM lysophosphatidylcholine has no effect on fatty acid oxidation and mitochondria remained impermeable in intact hepatocytes, 100 μM lysophosphatidylcholine inhibited fatty-acid stimulated oxidation and caused intracellular mitochondrial permeability. Taken together, these present data demonstrated that LPC concentration-dependently modulates mitochondrial microenvironment, with low micromolar concentrations of lysophosphatidylcholine sufficient to change hepatic oxidation rate whereas higher concentrations are required to disrupt mitochondrial integrity.

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Section: Discussionmentioning

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Micromolar changes in lysophosphatidylcholine concentration cause minor effects on mitochondrial permeability but major alterations in function

Hollie

Cash

Matlib

et al. 2014

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

Self Cite

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“…Accordingly, the reduced gastrointestinal production and absorption of lysophosphatidylcholine (LPC), a causal factor for insulin resistance, confers protection against diet-induced obesity, glucose intolerance, hyperlipidemia, and atherosclerosis in Pla2g1b Ϫ / Ϫ mice (40)(41)(42)(43).…”

Section: S Participate In Diverse Biologicalmentioning

confidence: 99%

A new era of secreted phospholipase A2

Murakami

Sato

Miki

et al. 2015

Journal of Lipid Research

204

170

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More than one third of the phospholipase A 2 (PLA 2 ) enzymes belong to the secreted PLA 2 (sPLA 2 ) family, which contains 10 catalytically active isoforms (IB, IIA, IIC, IID, IIE, IIF, III, V, X, and XIIA) and one inactive isoform (XIIB) in mammals ( 1-4 ). Individual sPLA 2 s exhibit unique tissue and cellular distributions and substrate selectivity, suggesting their distinct biological roles. Because sPLA 2 s are secreted and require millimolar Ca 2+ for their catalytic action, they principally target phospholipids in the extracellular space. Individual sPLA 2 s participate in diverse biological This work was supported by

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“…One of the major pathways for the formation of LPA is through the action of autotaxin on LysoPC ( 23 ). A major source of intestinal LysoPC is through the action of PLA2G1B (45)(46)(47)(48)(49)(50). PLA2G1B is a pancreatic PLA 2 that hydrolyzes fatty acids at the sn -2 position of phospholipids in the lumen of the small intestine.…”

Section: Searching For Natural Sources Of Intestinally Derived Lpamentioning

confidence: 99%

Source and role of intestinally derived lysophosphatidic acid in dyslipidemia and atherosclerosis

Navab

Chattopadhyay

Hough

et al. 2015

Journal of Lipid Research

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

Cited by 40 publications

References 36 publications

Micromolar changes in lysophosphatidylcholine concentration cause minor effects on mitochondrial permeability but major alterations in function

Micromolar changes in lysophosphatidylcholine concentration cause minor effects on mitochondrial permeability but major alterations in function

A new era of secreted phospholipase A2

Source and role of intestinally derived lysophosphatidic acid in dyslipidemia and atherosclerosis

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