The protective effect of fat specific protein 27 on tumor necrosis factor-alpha induced lipolysis and insulin resistance in human adipocytes
Adipose tissue is a key regulator of energy metabolism and glucose homeostasis by promoting triglyceride storage and breakdown in various physiological states. Obesity, however, alters adipose tissue metabolism, inducing chronic inflammation, followed by excessive lipolysis. This results in higher s...
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ndltd-bu.edu-oai-open.bu.edu-2144-139462019-12-07T03:02:52Z The protective effect of fat specific protein 27 on tumor necrosis factor-alpha induced lipolysis and insulin resistance in human adipocytes Lim, Amber Hyesuk Nutrition Cytokine Diabetes Fatty acid FSP27 Lipid droplet Obesity Adipose tissue is a key regulator of energy metabolism and glucose homeostasis by promoting triglyceride storage and breakdown in various physiological states. Obesity, however, alters adipose tissue metabolism, inducing chronic inflammation, followed by excessive lipolysis. This results in higher systemic free fatty acid (FFA) levels, leading to desensitization of insulin signaling and ultimately to insulin resistance. Although the link between obesity and progression of insulin resistance and type 2 diabetes mellitus (T2DM) remains unclear, tumor necrosis factor-alpha (TNF-alpha) has been proposed to be a key player in promoting obesity-related development of T2DM through chronic inflammation of adipose tissue. TNF-alpha has direct and indirect mechanisms by which it elicits insulin resistance in adipocytes. TNF-alpha attenuates insulin signaling by directly inhibiting insulin-stimulated tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 (IRS-1). Indirectly, TNF-alpha activates signaling pathways to increase lipolysis and FFA release into circulation, leading to insulin resistance. Lipid droplet-associated fat specific protein 27 (FSP27) protects adipocytes from lipolysis by regulating the lipolytic capacity as well as transcription of adipose triglyceride lipase (ATGL). It has been observed that TNF-alpha promotes lipolysis by reducing the expression of FSP27 in murine adipocytes. The effect of TNF-alpha on lipolysis human adipocytes has also been studied; yet its effect on promoting insulin resistance in human adipocytes still remains elusive. In the present study, we examined the effect of FSP27 on TNF-alpha induced lipolysis and insulin resistance in human adipocytes. TNF-alpha enhanced lipolysis in cultured human adipocytes. In addition, TNF-alpha reduced the expression of endogenous FSP7 and the phosphorylation of AKT, inhibiting the activation of insulin signaling pathway in cultured human adipocytes. FSP27 overexpression, however, attenuated TNF-alpha induced lipolysis and restored activation of insulin signaling through phosphorylation of AKT in cultured human adipocytes. Taken together, these data suggest that FSP27 has a protective effect against TNF-alpha induced lipolysis and insulin resistance through regulating lipolysis and insulin signaling in human adipocytes. 2016-01-08T18:40:03Z 2016-01-08T18:40:03Z 2015 2015-11-03T17:11:02Z Thesis/Dissertation https://hdl.handle.net/2144/13946 en_US |
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Nutrition Cytokine Diabetes Fatty acid FSP27 Lipid droplet Obesity |
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Nutrition Cytokine Diabetes Fatty acid FSP27 Lipid droplet Obesity Lim, Amber Hyesuk The protective effect of fat specific protein 27 on tumor necrosis factor-alpha induced lipolysis and insulin resistance in human adipocytes |
description |
Adipose tissue is a key regulator of energy metabolism and glucose homeostasis by promoting triglyceride storage and breakdown in various physiological states. Obesity, however, alters adipose tissue metabolism, inducing chronic inflammation, followed by excessive lipolysis. This results in higher systemic free fatty acid (FFA) levels, leading to desensitization of insulin signaling and ultimately to insulin resistance. Although the link between obesity and progression of insulin resistance and type 2 diabetes mellitus (T2DM) remains unclear, tumor necrosis factor-alpha (TNF-alpha) has been proposed to be a key player in promoting obesity-related development of T2DM through chronic inflammation of adipose tissue. TNF-alpha has direct and indirect mechanisms by which it elicits insulin resistance in adipocytes. TNF-alpha attenuates insulin signaling by directly inhibiting insulin-stimulated tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 (IRS-1). Indirectly, TNF-alpha activates signaling pathways to increase lipolysis and FFA release into circulation, leading to insulin resistance. Lipid droplet-associated fat specific protein 27 (FSP27) protects adipocytes from lipolysis by regulating the lipolytic capacity as well as transcription of adipose triglyceride lipase (ATGL). It has been observed that TNF-alpha promotes lipolysis by reducing the expression of FSP27 in murine adipocytes. The effect of TNF-alpha on lipolysis human adipocytes has also been studied; yet its effect on promoting insulin resistance in human adipocytes still remains elusive. In the present study, we examined the effect of FSP27 on TNF-alpha induced lipolysis and insulin resistance in human adipocytes. TNF-alpha enhanced lipolysis in cultured human adipocytes. In addition, TNF-alpha reduced the expression of endogenous FSP7 and the phosphorylation of AKT, inhibiting the activation of insulin signaling pathway in cultured human adipocytes. FSP27 overexpression, however, attenuated TNF-alpha induced lipolysis and restored activation of insulin signaling through phosphorylation of AKT in cultured human adipocytes. Taken together, these data suggest that FSP27 has a protective effect against TNF-alpha induced lipolysis and insulin resistance through regulating lipolysis and insulin signaling in human adipocytes. |
author |
Lim, Amber Hyesuk |
author_facet |
Lim, Amber Hyesuk |
author_sort |
Lim, Amber Hyesuk |
title |
The protective effect of fat specific protein 27 on tumor necrosis factor-alpha induced lipolysis and insulin resistance in human adipocytes |
title_short |
The protective effect of fat specific protein 27 on tumor necrosis factor-alpha induced lipolysis and insulin resistance in human adipocytes |
title_full |
The protective effect of fat specific protein 27 on tumor necrosis factor-alpha induced lipolysis and insulin resistance in human adipocytes |
title_fullStr |
The protective effect of fat specific protein 27 on tumor necrosis factor-alpha induced lipolysis and insulin resistance in human adipocytes |
title_full_unstemmed |
The protective effect of fat specific protein 27 on tumor necrosis factor-alpha induced lipolysis and insulin resistance in human adipocytes |
title_sort |
protective effect of fat specific protein 27 on tumor necrosis factor-alpha induced lipolysis and insulin resistance in human adipocytes |
publishDate |
2016 |
url |
https://hdl.handle.net/2144/13946 |
work_keys_str_mv |
AT limamberhyesuk theprotectiveeffectoffatspecificprotein27ontumornecrosisfactoralphainducedlipolysisandinsulinresistanceinhumanadipocytes AT limamberhyesuk protectiveeffectoffatspecificprotein27ontumornecrosisfactoralphainducedlipolysisandinsulinresistanceinhumanadipocytes |
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