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Leptin receptor-induced STAT3-independent signaling pathways are protective against atherosclerosis in a murine model of obesity and hyperlipidemia
W Luo, PF Bodary, Y Shen, KJ Wickenheiser... - Atherosclerosis, 2011 - Elsevier AIMS: Leptin is an adipocyte-derived hormone that has been shown to exert both beneficial metabolic effects and potentially adverse vascular effects in preclinical studies. The primary aim of this study was to determine the effects of leptin receptor signaling pathways on ...
Leptin is an adipocyte-derived hormone that has been shown to exert both beneficial metabolic effects and potentially adverse vascular effects in preclinical studies. The primary aim of this study was to determine the effects of leptin receptor signaling pathways on atherosclerosis in the setting of obesity and hyperlipidemia.
Mice were generated with deficiency of apolipoprotein E (Apo E / ) and either wild-type leptin receptor expression (Lepr+/+, Apo E / ), mutant leptin receptor expression defective in all leptin receptor signaling pathways (Leprdb/db, Apo E / ), or mutant leptin receptor expression with selective deficiency of leptin receptor-STAT3 signaling (Leprs/s, Apo E / ). At 27 weeks of age (including 7 weeks on a Western diet), Leprdb/db, Apo E / developed severe obesity, hypercholesterolemia, and increased atherosclerosis compared to Lepr+/+, Apo E / mice. Despite similar obesity and hyperlipidemia to Leprdb/db, Apo E / mice, Leprs/s, Apo E / developed less atherosclerosis than Leprdb/db, Apo E / mice. Adipose tissue macrophage content, monocyte chemoattractant protein-1 and fatty-acid-binding protein 4 levels were also reduced in Leprs/s, Apo E / mice compared to Leprdb/db, Apo E / mice.
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Leptin receptor-induced STAT3-independent signaling pathways are protective against atherosclerosis in a murine model of obesity and hyperlipidemia |
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