Growth hormone (GH) differentially regulates NF-kB activity in preadipocytes and macrophages: implications for GH�s role in adipose tissue homeostasis in obesity

• Autores: P. Anil Kumar, P. Swathi Chitra, Chunxia Lu, J. Sobhanaditya, Ram K. Menon
• Localización: Journal of physiology and biochemistry, ISSN-e 1877-8755, ISSN 1138-7548, Vol. 70, Nº. 2, 2014 (Ejemplar dedicado a: Special Section on the CTP network: Original papers from the 10th meeting of the CTPIOD (Contribution To Progress in Obesity and Diabetes Research), 22th of May 2013, Reus, Spain.), págs. 433-440
• Idioma: inglés
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• Resumen

  • Adipose tissue remodeling in obesity involves macrophage infiltration and chronic inflammation. NF-kB-mediated chronic inflammation of the adipose tissue is directly implicated in obesity-associated insulin resistance. We have investigated the effect of growth hormone (GH) on NF-kB activity in preadipocytes (3T3-F442A) and macrophages (J774A.1). Our studies indicate that whereas GH increases NF-kB activity in preadipocytes, it decreases NF-kB activity in macrophages. This differential response of NF-kB activity to GH correlates with the GH-dependent expression of a cadre of NF-kB-activated cytokines in these two cell types. Activation of NF-kB by GH in preadipocytes heightens inflammatory response by stimulating production of multiple cytokines including TNF-?, IL-6, and MCP-1, the mediators of both local and systemic insulin resistance and chemokines that recruit macrophages. Our studies also suggest differential regulation of miR132 and SIRT1 expression as a mechanism underlying the observed variance in GH-dependent NF-kB activity and altered cytokine profile in preadipocytes and macrophages. These findings further our understanding of the complex actions of GH on adipocytes and insulin sensitivity.