Fat-specific Protein 27 (FSP27) Interacts with Adipose Triglyceride Lipase (ATGL) to Regulate Lipolysis and Insulin Sensitivity in Human Adipocytes

Grahn, Tan Hooi Min; Kaur, Rajween; Yin, Jun; Schweiger, Martina; Sharma, Vishva Mitra; Lee, Mi‐Jeong; Ido, Yasuo; Smas, Cynthia M.; Zechner, Rudolf; Lass, Achim; Puri, Vishwajeet

doi:10.1074/jbc.m113.539890

Cited by 110 publications

(109 citation statements)

References 64 publications

(103 reference statements)

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“…The latter protein plays an essential role in the regulation of LD morphology. Depletion of FSP27 in adipocytes leads to fragmentation of LDs (11,12), whereas overexpression of FSP27 increases the size of LDs while decreasing their number (8, 9, 12) by promoting LD fusion (13) and exchanging lipids from one droplet to another (14).It has also been demonstrated by us and others that FSP27 has anti-lipolytic activity (8,9,12,(15)(16)(17)(18). Lipolysis in adipose tissue is the major source of circulating .…”

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confidence: 97%

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Fat-specific Protein 27 Inhibits Lipolysis by Facilitating the Inhibitory Effect of Transcription Factor Egr1 on Transcription of Adipose Triglyceride Lipase

Singh

Kaur

Lee

et al. 2014

Journal of Biological Chemistry

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Background: FSP27 is a lipid droplet-associated protein.Results: Expression of FSP27 in human adipocytes reversely correlates with ATGL levels. Mechanistically, FSP27 increases the inhibitory effect of Egr1 on the ATGL promoter. Conclusion: FSP27 controls lipolysis by regulating ATGL transcription. Significance: Our study provides a new model of regulation of lipolysis in adipocytes. Current epidemics of metabolic diseases, such as type 2 diabetes, cardiac dysfunction, hypertension, hepatic steatosis, etc., are largely caused by widespread obesity. Although obesity can affect human health via several different mechanisms (1), the best established connection between obesity and metabolic disease is abnormal levels of circulating fatty acids (FA). 3 FA play important physiological roles in energy production and the synthesis of most lipids; nonetheless, their oversupply is highly detrimental as it leads to insulin resistance, oxidative stress, and other pathophysiological effects via mechanisms that are currently under intense investigation (1-5). Lipolysis in fat tissueNormally, dietary FA are partitioned into adipose tissue, converted into triglycerides, and stored in lipid droplets (LDs) that represent dynamic intracellular organelles consisting of a core of triglycerides and cholesterol esters, surrounded by a monolayer of phospholipids. Several proteins are associated with this monolayer, notably the PAT family proteins, PLIN 1-5 (6, 7), and fat-specific protein 27 (FSP27, also known as CIDEC) (8 -10). The latter protein plays an essential role in the regulation of LD morphology. Depletion of FSP27 in adipocytes leads to fragmentation of LDs (11,12), whereas overexpression of FSP27 increases the size of LDs while decreasing their number (8, 9, 12) by promoting LD fusion (13) and exchanging lipids from one droplet to another (14).It has also been demonstrated by us and others that FSP27 has anti-lipolytic activity (8,9,12,(15)(16)(17)(18). Lipolysis in adipose tissue is the major source of circulating . Correspondingly, unrestricted lipolysis in adipose tissue represents a serious metabolic defect and a causative factor of insulin resistance, diabetes mellitus, and other metabolic diseases (3,(25)(26)(27). As the mechanism of the anti-lipolytic activity of FSP27 is not completely clear, we decided to focus on this problem.Our recent study showed that FSP27 directly interacts with ATGL and regulates its lipase activity (18). Another study predicted that FSP27-mediated fusion of LDs might limit the access of intracellular lipases to the LD surface due to decreased surface area of larger LDs (17). As ATGL represents a major lipolytic enzyme (28), reducing its contact with LDs may suppress lipolysis.Here, we report another mechanism of the anti-lipolytic action of FSP27 in human adipocytes. We have found that FSP27 inhibits expression of ATGL at the level of transcription by stimulating the effect of its transcriptional repressor Egr1. EXPERIMENTAL PROCEDURESCell Culture-Human preadipocytes were procured from the ...

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confidence: 97%

“…It has also been demonstrated by us and others that FSP27 has anti-lipolytic activity (8,9,12,(15)(16)(17)(18). Lipolysis in adipose tissue is the major source of circulating FA (19 -24).…”

mentioning

confidence: 99%

Fat-specific Protein 27 Inhibits Lipolysis by Facilitating the Inhibitory Effect of Transcription Factor Egr1 on Transcription of Adipose Triglyceride Lipase

Singh

Kaur

Lee

et al. 2014

Journal of Biological Chemistry

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“…Fsp27 is a protein in adipocytes and regulates both basal and stimulated lipolysis by interacting with adipose triacylglycerol lipase (ATGL). FSP27-ATGL interactions play a crucial role in regulating lipolysis, triacylglycerol accumulation and insulin signaling in human adipocytes (89). So far, the effect of niacin treatment has not been explicitly proven in patients with NAFLD.…”

Section: Impact Of Niacin On Non-alcoholic Fatty Liver Diseasementioning

confidence: 99%

Pleiotropic effects of niacin: Current possibilities for its clinical use

et al. 2016

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Niacin was the first hypolipidemic drug to significantly reduce both major cardiovascular events and mortality in patients with cardiovascular disease. Niacin favorably influences all lipoprotein classes, including lipoprotein [a],and belongs to the most potent hypolipidemic drugs for increasing HDL-C. Moreover, niacin causes favorable changes to the qualitative composition of lipoprotein HDL. In addition to its pronounced hypolipidemic action, niacin exerts many other, non-hypolipidemic effects (e.g., antioxidative, anti-inflammatory, antithrombotic), which favorably influence the development and progression of atherosclerosis. These effects are dependent on activation of the specific receptor HCA2. Recent results published by the two large clinical studies, AIM-HIGH and HPS2-THRIVE, have led to the impugnation of niacin's role in future clinical practice. However, due to several methodological flaws in the AIM-HIGH and HPS2-THRIVE studies, the pleiotropic effects of niacin now deserve thorough evaluation. This review summarizes the present and possible future use of niacin in clinical practice in light of its newly recognized pleiotropic effects.

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“…Under basal conditions, Plin1 is associated with CGI-58 on the LD surface, and when Plin1 is phosphorylated by PKA, CGI-58 is released and can interact with ATGL, thereby increasing its activity (Lass et al, 2006). Fsp27 also plays a double role in the regulation of ATGL activity: in the LD it inhibits lipolysis by binding to ATGL (Grahn et al, 2014), whereas in the nucleus it potentiates Erg1-negative regulation of the ATGL promoter (Singh et al, 2014).…”

Section: Lipid Dropletsmentioning

confidence: 99%

Role of bioactive lipid mediators in obese adipose tissue inflammation and endocrine dysfunction

Lopategi

López‐Vicario

Alcaraz‐Quiles

et al. 2016

Molecular and Cellular Endocrinology

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a b s t r a c tWhite adipose tissue is recognized as an active endocrine organ implicated in the maintenance of metabolic homeostasis. However, adipose tissue function, which has a crucial role in the development of obesity-related comorbidities including insulin resistance and non-alcoholic fatty liver disease, is dysregulated in obese individuals. This review explores the physiological functions and molecular actions of bioactive lipids biosynthesized in adipose tissue including sphingolipids and phospholipids, and in particular fatty acids derived from phospholipids of the cell membrane. Special emphasis is given to polyunsaturated fatty acids of the omega-6 and omega-3 families and their conversion to bioactive lipid mediators through the cyclooxygenase and lipoxygenase pathways. The participation of omega-3-derived lipid autacoids in the resolution of adipose tissue inflammation and in the prevention of obesity-associated hepatic complications is also thoroughly discussed.

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Fat-specific Protein 27 (FSP27) Interacts with Adipose Triglyceride Lipase (ATGL) to Regulate Lipolysis and Insulin Sensitivity in Human Adipocytes

Cited by 110 publications

References 64 publications

Fat-specific Protein 27 Inhibits Lipolysis by Facilitating the Inhibitory Effect of Transcription Factor Egr1 on Transcription of Adipose Triglyceride Lipase

Fat-specific Protein 27 Inhibits Lipolysis by Facilitating the Inhibitory Effect of Transcription Factor Egr1 on Transcription of Adipose Triglyceride Lipase

Pleiotropic effects of niacin: Current possibilities for its clinical use

Role of bioactive lipid mediators in obese adipose tissue inflammation and endocrine dysfunction

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