An inhibitor of phospholipase A2 group IIA modulates adipocyte signaling and protects against diet-induced metabolic syndrome in rats
Article
Article Title | An inhibitor of phospholipase A2 group IIA modulates adipocyte signaling and protects against diet-induced metabolic syndrome in rats |
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ERA Journal ID | 16015 |
Article Category | Article |
Authors | Iyer, Abishek (Author), Lim, Junxian (Author), Poudyal, Hemant (Author), Reid, Robert C. (Author), Suen, Jacky Y. (Author), Webster, Julie (Author), Prins, Johannes B. (Author), Whitehead, Jonathan P. (Author), Fairlie, David P. (Author) and Brown, Lindsay (Author) |
Journal Title | Diabetes |
Journal Citation | 61 (9), pp. 2320-2329 |
Number of Pages | 10 |
Year | 2012 |
Place of Publication | Alexandria, VA. United States |
ISSN | 0012-1797 |
1939-327X | |
Digital Object Identifier (DOI) | https://doi.org/10.2337/db11-1179 |
Web Address (URL) | http://diabetes.diabetesjournals.org/content/61/9/2320.abstract?sid=70f368c8-15ea-4f4d-8682-8085ade847ad |
Abstract | Obesity, type 2 diabetes, and cardiovascular disease correlate with infiltration to adipose tissue of different immune cells, with uncertain influences on metabolism. Rats were fed a diet high in carbohydrates and saturated fats to develop diet-induced obesity over 16 weeks. This nutritional overload caused overexpression and secretion of phospholipase A2 group IIA (pla2g2a) from immune cells in adipose tissue rather than adipocytes, whereas expression of adipose-specific phospholipase A2 (pla2g16) was unchanged. These immune cells produce prostaglandin E2 (PGE2), which influences adipocyte signaling. We found that a selective inhibitor of human pla2g2a (5-(4-benzyloxyphenyl)-(4S)-(phenyl-heptanoylamino)-pentanoic acid [KH064]) attenuated secretion of PGE2 from human immune cells stimulated with the fatty acid, palmitic acid, or with lipopolysaccharide. Oral administration of KH064 (5 mg/kg/day) to rats fed the high-carbohydrate, high-fat diet prevented the overexpression of pla2g2a and the increased macrophage infiltration and elevated PGE2 concentrations in adipose tissue. The treatment also attenuated visceral adiposity and reversed most characteristics of metabolic syndrome, producing marked improvements in insulin sensitivity, glucose intolerance, and cardiovascular abnormalities. We suggest that pla2g2a may have a causal relationship with chronic adiposity and metabolic syndrome and that its inhibition in vivo may be a valuable new approach to treat obesity, type 2 diabetes, and metabolic dysfunction in humans. |
Keywords | fatty tissue; high-fat diet; rats; obese |
ANZSRC Field of Research 2020 | 320502. Medical biochemistry - carbohydrates |
320507. Metabolic medicine | |
320699. Medical biotechnology not elsewhere classified | |
Byline Affiliations | University of Queensland |
Mater Group, Australia | |
Department of Biological and Physical Sciences | |
Institution of Origin | University of Southern Queensland |
https://research.usq.edu.au/item/q17vz/an-inhibitor-of-phospholipase-a2-group-iia-modulates-adipocyte-signaling-and-protects-against-diet-induced-metabolic-syndrome-in-rats
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