Reduced mRNA and Protein Expression of Perilipin A and G0/G1 Switch Gene 2 (G0S2) in Human Adipose Tissue in Poorly Controlled Type 2 Diabetes

Nielsen, Thomas S.; Kampmann, Ulla; Nielsen, Roni; Jessen, Niels; Ørskov, L.; Pedersen, Steen B.; Jørgensen, Jens Otto Lunde; Lund, Sten; Møller, Niels

doi:10.1210/jc.2012-1159

Cited by 28 publications

(26 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The fi nding that G0S2 mRNA and protein expression is reduced in adipose tissue of type 2 diabetic humans suggests that enhanced ATGL activity may contribute to elevated lipolysis and plasma FA levels in type 2 diabetic patients ( 20 ). Considering the nutritional and hormonal regulation of G0S2, downregulation of this protein could represent one of the underlying mechanisms causing increased lipolysis in the insulinresistant state.…”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, the antilipolytic hormone insulin increases G0S2 expression in murine 3T3 cells, whereas stimulation of lipolysis by ␤ -adrenergic agonists and tumor necrosis factor-␣ has the opposite effect ( 13,19 ). Importantly, a recent report demonstrated that G0S2 mRNA and protein expression is reduced in adipose tissue of type 2 diabetic humans, indicating that enhanced ATGL activity contributes to elevated lipolysis and plasma fatty acid (FA) levels in type 2 diabetes ( 20 ).…”

Section: Sequence Analysismentioning

confidence: 99%

See 1 more Smart Citation

G0/G1 switch gene-2 regulates human adipocyte lipolysis by affecting activity and localization of adipose triglyceride lipase

Schweiger

Paar

Eder

et al. 2012

Journal of Lipid Research

View full text Add to dashboard Cite

Supplementary key words comparative gene identifi cation-58 • human lipolysis • regulation • insulin resistanceIn periods of nutrient scarcity or in response to increased energy demand, triglyceride (TG) stores are mobilized to provide free fatty acids (FFAs) as energy fuel. The mobilization of TGs is performed in three consecutive reactions, catalyzed by three lipases: adipose triglyceride lipase (ATGL) ( 1-3 ), hormone-sensitive lipase (HSL) ( 4 ), and monoglyceride lipase (MGL) ( 5 ). The crucial physiological role of ATGL (also annotated as patatin-like phospholipase domain containing 2, desnutrin, phospholipase A2 , and transport secretion protein 2.2) in lipolysis became evident by the phenotype of ATGL-defi cient (ATGL-ko) mice. ATGL-ko mice display increased whole-body fat mass, enlarged adipose fat depots, and TG accumulation in many tissues. Massive TG deposition in cardiomyocytes leads to cardiac insuffi ciency and premature death ( 6 ). In humans, the lack of ATGL activity, caused by mutations in the ATGL gene, is associated with a rare inherited disorder, annotated as neutral lipid storage disease with myopathy (NLSDM) ( 7 ). This disease is characterized by TG deposition in multiple tissues and cardiac myopathy.ATGL activity is strongly infl uenced by regulatory proteins. In 2006, Lass et al. identifi ed comparative gene identifi cation-58 (CGI-58, also known as ABHD5) as coactivator of Abstract The hydrolysis of triglycerides in adipocytes, termed lipolysis, provides free fatty acids as energy fuel. Murine lipolysis largely depends on the activity of adipose triglyceride lipase (ATGL), which is regulated by two proteins annotated as comparative gene identifi cation-58 (CGI-58) and G0/G1 switch gene-2 (G0S2). CGI-58 activates and G0S2 inhibits ATGL activity. In contrast to mice, the functional role of G0S2 in human adipocyte lipolysis is poorly characterized. Here we show that overexpression or silencing of G0S2 in human SGBS adipocytes decreases and increases lipolysis, respectively. Human G0S2 is upregulated during adipocyte differentiation and inhibits ATGL activity in a dose-dependent manner. Interestingly, C-terminally truncated ATGL mutants, which fail to localize to lipid droplets, translocate to the lipid droplet upon coexpression with G0S2, suggesting that G0S2 anchors ATGL to lipid droplets independent of ATGL's C-terminal lipid binding domain. Taken together, our results indicate that G0S2 also regulates human lipolysis by affecting enzyme activity and intracellular localization of ATGL. Increased lipolysis is known to contribute to the pathogenesis of insulin resistance, and G0S2 expression has been shown to be reduced in poorly controlled type 2 diabetic patients. Our data indicate that downregulation of G0S2 in adipose tissue could represent one of the underlying causes leading to increased lipolysis in the insulin-resistant state. -Schweiger, M., M. Paar, C. Eder, J. Brandis, E. Moser, G. Gorkiewicz, S. Grond, F. P. W. Radner, I. Cerk, I. Cornaciu, M. Oberer, S. Kersten, R. Zechner, ...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Sequence Analysismentioning

confidence: 99%

G0/G1 switch gene-2 regulates human adipocyte lipolysis by affecting activity and localization of adipose triglyceride lipase

Schweiger

Paar

Eder

et al. 2012

Journal of Lipid Research

View full text Add to dashboard Cite

show abstract

“…Similarly, increased FFA mobilization was found in type 2 diabetic patients following 16 h of hypoinsulinemia (15). Notably, no change was found in adipose tissue HSL phosphorylation while G0S2 was decreased, clearly suggesting a distinct increase in basal lipolysis (15). Importantly, G0S2 does indeed regulate ATGL activity in human fat cells (9), and fasting-induced reductions in G0S2 expression have also been found in adipose tissue from birds (16) and pigs (17), indicating that this regulatory mechanism is highly conserved.…”

mentioning

confidence: 73%

“…Indeed, it has previously been shown in humans that elevated FFA mobilization during prolonged fasting is associated with a substantial decrease in G0S2 in adipose tissue (14). Similarly, increased FFA mobilization was found in type 2 diabetic patients following 16 h of hypoinsulinemia (15). Notably, no change was found in adipose tissue HSL phosphorylation while G0S2 was decreased, clearly suggesting a distinct increase in basal lipolysis (15).…”

mentioning

confidence: 84%

Adipose Triglyceride Lipase and G0/G1 Switch Gene 2: Approaching Proof of Concept

Nielsen

Møller

2014

Diabetes

Self Cite

View full text Add to dashboard Cite

“…Yet, it has been shown that human G0S2 inhibits human ATGL in a dosedependent manner [20]. Furthermore, human G0S2 is downregulated in WAT by fasting and in individuals with poorly controlled type 2 diabetes [21,22]. Unfortunately, to date, Fig.…”

mentioning

confidence: 99%

The sparing use of fat: G0s2 controls lipolysis and fatty acid oxidation

Heier

Zimmermann

2014

Diabetologia

View full text Add to dashboard Cite

Reduced mRNA and Protein Expression of Perilipin A and G0/G1 Switch Gene 2 (G0S2) in Human Adipose Tissue in Poorly Controlled Type 2 Diabetes

Cited by 28 publications

References 20 publications

G0/G1 switch gene-2 regulates human adipocyte lipolysis by affecting activity and localization of adipose triglyceride lipase

G0/G1 switch gene-2 regulates human adipocyte lipolysis by affecting activity and localization of adipose triglyceride lipase

Adipose Triglyceride Lipase and G0/G1 Switch Gene 2: Approaching Proof of Concept

The sparing use of fat: G0s2 controls lipolysis and fatty acid oxidation

Contact Info

Product

Resources

About