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

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Abstract

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-α, 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.

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Acknowledgments

Work in the authors’ laboratory was supported by the DST-INSPIRE Faculty Programme, INDIA (PAK) and NIH, USA (RKM).

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Authors and Affiliations

  1. National Institute of Nutrition, Hyderabad, 500007, India

    P. Anil Kumar

  2. IGNOU, New Delhi, India

    P. Swathi Chitra

  3. Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI, USA

    Chunxia Lu & Ram Menon

  4. Osmania University, Hyderabad, India

    J. Sobhanaditya

  5. Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA

    Ram Menon

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  1. P. Anil Kumar
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  2. P. Swathi Chitra
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  4. J. Sobhanaditya
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  5. Ram Menon
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Correspondence to P. Anil Kumar.

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Kumar, P.A., Chitra, P.S., Lu, C. et al. Growth hormone (GH) differentially regulates NF-kB activity in preadipocytes and macrophages: implications for GH’s role in adipose tissue homeostasis in obesity. J Physiol Biochem 70, 433–440 (2014). https://doi.org/10.1007/s13105-014-0321-8

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  • DOI: https://doi.org/10.1007/s13105-014-0321-8

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