西亚试剂：Salicylate Blocks Lipolytic Actions of Tumor Necrosis Facto

Salicylate Blocks Lipolytic Actions of Tumor Necrosis Factor-TNF- in Primary Rat Adipocytes

Luxia Zu 1, Hongfeng Jiang 1, Jinhan He 1, Chong Xu 1, Shenshen Pu 1, Meifang Liu 1, Guoheng Xu 1*

1 Peking University Health Science Center

* Address correspondence to: E-mail: xug@bjmu.edu.cn

Abstract

Increased systemic free fatty acids (FFA) impair insulin sensitivity. In obese and diabetic subjects, production of a proinflammatory cytokine, tumor necrosis factor- (TNF-), is elevated. TNF- has a variety of effects by inducing inflammation, decreasing glucose utilization, and also stimulating adipocyte lipolysis to release FFA to plasma. High doses of nonsteroidal anti-inflammatory drug salicylates have been long recognized to lower blood FFA and glucose in humans, although the mechanisms are not fully understood. In this report, we show that sodium salicylate at therapeutic concentrations directly blocks TNF--stimulated lipolysis and therefore inhibits FFA release from primary rat adipocytes. To elucidate the cellular basis of this action, we show that salicylate suppresses TNF--induced extracellular signal-related kinase activation and intracellular cAMP elevation, two early events during the lipolysis response to TNF-. Further, salicylate prevents the downregulation of cyclic-nucleotide phosphodiesterase 3B, an enzyme responsible for cAMP hydrolysis. Perilipins coat intracellular lipid droplet surface by restricting lipase access to the triacylglycerol substrates. TNF- downregulates perilipin but promotes its phosphorylation during lipolysis stimulation; these actions are efficiently reversed by salicylate. Salicylate slightly reduces basal but completely inhibits TNF--liberated lipase activity. In contrast, neither salicylate nor TNF- alters the protein levels of hormone-sensitive lipase and adipose triglyceride lipase. In addition, sodium salicylate restricts basal lipolysis simulated by a high concentration of glucose and significantly diminishes the high glucose-enhanced lipolysis response to TNF-. These results provide novel evidence that salicylate directly blocks TNF--mediated FFA efflux from adipocytes, hence reducing plasma FFA levels and increasing insulin sensitivity.

Key words: Tumor necrosis factor, cAMP, Protein Kinase A, MAP Kinase

• 以上资料由西亚试剂：http://www.xiyashiji.com/ 提供此产品的详细信息如密度,含量,分子式,分子量等均可在西亚官网查询   
• 相关产品如溴化汞硝酸亚汞氯化亚汞乙酸苯汞氯化钾汞 碘化汞钾硫氰酸汞硫酸亚汞氧化汞氯化汞碘化汞硝酸汞三氯氧磷三氯化磷碘甲烷二碘甲烷三碘甲烷三氟碘甲烷氘代碘甲烷碘乙烷1,2-二碘乙烷甲酸铷碘化铷溴化铷铬酸铷硫酸铷氟化铷硝酸铷氯化铷碳酸铷硫酸镱 碳酸镱氯化镱硝酸镱氧化镱等均有销售.欢迎订购