The role of adhydrolase domain containing protein 15 (ABHD15) in insulin-mediated suppression of lipolysis

Wenmin XIA, Ariane Pessentheiner, Evelyn Walenta, Thomas Rülicke, Renate Schreiber, Dina Hofer, Melina Amor, Juliane Gertrude Bogner-Strauß

Publikation: KonferenzbeitragPosterForschung

Abstract

Background and Aims: Adipose tissue (AT) is a multi-functional organ which plays an important role in lipid and glucose homeostasis. Dysfunction of lipid and glucose metabolism in AT leads to insulin resistance and contributes to the development of obesity and type II diabetes. In mouse 3T3L1 adipocytes, ABHD15 has been identified as a phosphorylation substrate of Akt/PKB in insulin signalling. Moreover, it interacts with phosphodiesterase 3B (PDE3B) by protein-protein interaction. PDE3B itself plays an important role in insulin-mediated suppression of lipolysis in adipocytes. Thereby, we hypothesize that ABHD15 plays a role in insulin-regulated lipolysis in AT. Results: ABHD15 is highly expressed in white adipose tissue (WAT) and to a lower extent in liver. In mice, fasting strongly decreased ABHD15 expression while refeeding increased its expression in WAT. We generated whole body ABHD15-knockout (KO) mice and characterized them with regard to lipid metabolism. Interestingly, after an insulin bolus, ABHD15-KO mice did not repress lipolysis as they showed highly increased plasma FFA and glycerol levels in comparison to wt mice. Accordingly, the phosphorylation of Akt and the dephosphorylation of protein kinase A (PKA) and HSL by insulin were strongly impaired in ABHD15-KO mice. Increased FFAs in the circulation often lead to insulin resistance. Young ABHD15-KO mice showed similar insulin sensitivity as wt mice. However, ABHD15-KO mice became insulin resistant upon aging. Further, ABHD15-KO mice showed decreased postprandial plasma adiponectin levels on chow or high glucose diet (HGD) at young age. In addition, HGD-challenged ABHD15-KO mice had higher postprandial plasma insulin and glucose levels. Consistently, also insulin-suppressed FFA release from WAT was impaired in HGD-fed ABHD15-KO mice. We explored the mechanism behind this phenotype and found that ABHD15 decreased the activity and expression of its interaction partner PDE3B in vitro. Interestingly, PDE3B expression was also substantially decreased in AT of ABHD15-KO mice. Conclusion: In WAT, ABHD15 is required for insulin-mediated suppression of lipolysis. The mechanism behind is still under investigation, however our data reveal that ABHD15 binds PDE3B and regulates its expression in vitro and that knock-down of ABHD15 in vivo strongly decreases PDE3B mRNA and protein expression and might thereby decrease insulin-mediated suppression of lipolysis by increasing pHSL and pPKA levels.
Originalspracheenglisch
PublikationsstatusEingereicht - 7 Mär 2017

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Lipolysis
Type 3 Cyclic Nucleotide Phosphodiesterases
Knockout Mice
Insulin
White Adipose Tissue
Glucose
Adipose Tissue
Insulin Resistance
Diet
Lipid Metabolism
Adipocytes
Phosphorylation
Protein Domains
Proteins
Adiponectin
Cyclic AMP-Dependent Protein Kinases
Glycerol
Type 2 Diabetes Mellitus
Fasting
Homeostasis

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XIA, W., Pessentheiner, A., Walenta, E., Rülicke, T., Schreiber, R., Hofer, D., ... Bogner-Strauß, J. G. (2017). The role of adhydrolase domain containing protein 15 (ABHD15) in insulin-mediated suppression of lipolysis.

The role of adhydrolase domain containing protein 15 (ABHD15) in insulin-mediated suppression of lipolysis. / XIA, Wenmin; Pessentheiner, Ariane; Walenta, Evelyn; Rülicke, Thomas; Schreiber, Renate; Hofer, Dina; Amor, Melina; Bogner-Strauß, Juliane Gertrude.

2017.

Publikation: KonferenzbeitragPosterForschung

XIA W, Pessentheiner A, Walenta E, Rülicke T, Schreiber R, Hofer D et al. The role of adhydrolase domain containing protein 15 (ABHD15) in insulin-mediated suppression of lipolysis. 2017.
XIA, Wenmin ; Pessentheiner, Ariane ; Walenta, Evelyn ; Rülicke, Thomas ; Schreiber, Renate ; Hofer, Dina ; Amor, Melina ; Bogner-Strauß, Juliane Gertrude. / The role of adhydrolase domain containing protein 15 (ABHD15) in insulin-mediated suppression of lipolysis.
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abstract = "Background and Aims: Adipose tissue (AT) is a multi-functional organ which plays an important role in lipid and glucose homeostasis. Dysfunction of lipid and glucose metabolism in AT leads to insulin resistance and contributes to the development of obesity and type II diabetes. In mouse 3T3L1 adipocytes, ABHD15 has been identified as a phosphorylation substrate of Akt/PKB in insulin signalling. Moreover, it interacts with phosphodiesterase 3B (PDE3B) by protein-protein interaction. PDE3B itself plays an important role in insulin-mediated suppression of lipolysis in adipocytes. Thereby, we hypothesize that ABHD15 plays a role in insulin-regulated lipolysis in AT. Results: ABHD15 is highly expressed in white adipose tissue (WAT) and to a lower extent in liver. In mice, fasting strongly decreased ABHD15 expression while refeeding increased its expression in WAT. We generated whole body ABHD15-knockout (KO) mice and characterized them with regard to lipid metabolism. Interestingly, after an insulin bolus, ABHD15-KO mice did not repress lipolysis as they showed highly increased plasma FFA and glycerol levels in comparison to wt mice. Accordingly, the phosphorylation of Akt and the dephosphorylation of protein kinase A (PKA) and HSL by insulin were strongly impaired in ABHD15-KO mice. Increased FFAs in the circulation often lead to insulin resistance. Young ABHD15-KO mice showed similar insulin sensitivity as wt mice. However, ABHD15-KO mice became insulin resistant upon aging. Further, ABHD15-KO mice showed decreased postprandial plasma adiponectin levels on chow or high glucose diet (HGD) at young age. In addition, HGD-challenged ABHD15-KO mice had higher postprandial plasma insulin and glucose levels. Consistently, also insulin-suppressed FFA release from WAT was impaired in HGD-fed ABHD15-KO mice. We explored the mechanism behind this phenotype and found that ABHD15 decreased the activity and expression of its interaction partner PDE3B in vitro. Interestingly, PDE3B expression was also substantially decreased in AT of ABHD15-KO mice. Conclusion: In WAT, ABHD15 is required for insulin-mediated suppression of lipolysis. The mechanism behind is still under investigation, however our data reveal that ABHD15 binds PDE3B and regulates its expression in vitro and that knock-down of ABHD15 in vivo strongly decreases PDE3B mRNA and protein expression and might thereby decrease insulin-mediated suppression of lipolysis by increasing pHSL and pPKA levels.",
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T1 - The role of adhydrolase domain containing protein 15 (ABHD15) in insulin-mediated suppression of lipolysis

AU - XIA, Wenmin

AU - Pessentheiner, Ariane

AU - Walenta, Evelyn

AU - Rülicke, Thomas

AU - Schreiber, Renate

AU - Hofer, Dina

AU - Amor, Melina

AU - Bogner-Strauß, Juliane Gertrude

PY - 2017/3/7

Y1 - 2017/3/7

N2 - Background and Aims: Adipose tissue (AT) is a multi-functional organ which plays an important role in lipid and glucose homeostasis. Dysfunction of lipid and glucose metabolism in AT leads to insulin resistance and contributes to the development of obesity and type II diabetes. In mouse 3T3L1 adipocytes, ABHD15 has been identified as a phosphorylation substrate of Akt/PKB in insulin signalling. Moreover, it interacts with phosphodiesterase 3B (PDE3B) by protein-protein interaction. PDE3B itself plays an important role in insulin-mediated suppression of lipolysis in adipocytes. Thereby, we hypothesize that ABHD15 plays a role in insulin-regulated lipolysis in AT. Results: ABHD15 is highly expressed in white adipose tissue (WAT) and to a lower extent in liver. In mice, fasting strongly decreased ABHD15 expression while refeeding increased its expression in WAT. We generated whole body ABHD15-knockout (KO) mice and characterized them with regard to lipid metabolism. Interestingly, after an insulin bolus, ABHD15-KO mice did not repress lipolysis as they showed highly increased plasma FFA and glycerol levels in comparison to wt mice. Accordingly, the phosphorylation of Akt and the dephosphorylation of protein kinase A (PKA) and HSL by insulin were strongly impaired in ABHD15-KO mice. Increased FFAs in the circulation often lead to insulin resistance. Young ABHD15-KO mice showed similar insulin sensitivity as wt mice. However, ABHD15-KO mice became insulin resistant upon aging. Further, ABHD15-KO mice showed decreased postprandial plasma adiponectin levels on chow or high glucose diet (HGD) at young age. In addition, HGD-challenged ABHD15-KO mice had higher postprandial plasma insulin and glucose levels. Consistently, also insulin-suppressed FFA release from WAT was impaired in HGD-fed ABHD15-KO mice. We explored the mechanism behind this phenotype and found that ABHD15 decreased the activity and expression of its interaction partner PDE3B in vitro. Interestingly, PDE3B expression was also substantially decreased in AT of ABHD15-KO mice. Conclusion: In WAT, ABHD15 is required for insulin-mediated suppression of lipolysis. The mechanism behind is still under investigation, however our data reveal that ABHD15 binds PDE3B and regulates its expression in vitro and that knock-down of ABHD15 in vivo strongly decreases PDE3B mRNA and protein expression and might thereby decrease insulin-mediated suppression of lipolysis by increasing pHSL and pPKA levels.

AB - Background and Aims: Adipose tissue (AT) is a multi-functional organ which plays an important role in lipid and glucose homeostasis. Dysfunction of lipid and glucose metabolism in AT leads to insulin resistance and contributes to the development of obesity and type II diabetes. In mouse 3T3L1 adipocytes, ABHD15 has been identified as a phosphorylation substrate of Akt/PKB in insulin signalling. Moreover, it interacts with phosphodiesterase 3B (PDE3B) by protein-protein interaction. PDE3B itself plays an important role in insulin-mediated suppression of lipolysis in adipocytes. Thereby, we hypothesize that ABHD15 plays a role in insulin-regulated lipolysis in AT. Results: ABHD15 is highly expressed in white adipose tissue (WAT) and to a lower extent in liver. In mice, fasting strongly decreased ABHD15 expression while refeeding increased its expression in WAT. We generated whole body ABHD15-knockout (KO) mice and characterized them with regard to lipid metabolism. Interestingly, after an insulin bolus, ABHD15-KO mice did not repress lipolysis as they showed highly increased plasma FFA and glycerol levels in comparison to wt mice. Accordingly, the phosphorylation of Akt and the dephosphorylation of protein kinase A (PKA) and HSL by insulin were strongly impaired in ABHD15-KO mice. Increased FFAs in the circulation often lead to insulin resistance. Young ABHD15-KO mice showed similar insulin sensitivity as wt mice. However, ABHD15-KO mice became insulin resistant upon aging. Further, ABHD15-KO mice showed decreased postprandial plasma adiponectin levels on chow or high glucose diet (HGD) at young age. In addition, HGD-challenged ABHD15-KO mice had higher postprandial plasma insulin and glucose levels. Consistently, also insulin-suppressed FFA release from WAT was impaired in HGD-fed ABHD15-KO mice. We explored the mechanism behind this phenotype and found that ABHD15 decreased the activity and expression of its interaction partner PDE3B in vitro. Interestingly, PDE3B expression was also substantially decreased in AT of ABHD15-KO mice. Conclusion: In WAT, ABHD15 is required for insulin-mediated suppression of lipolysis. The mechanism behind is still under investigation, however our data reveal that ABHD15 binds PDE3B and regulates its expression in vitro and that knock-down of ABHD15 in vivo strongly decreases PDE3B mRNA and protein expression and might thereby decrease insulin-mediated suppression of lipolysis by increasing pHSL and pPKA levels.

M3 - Poster

ER -