Growth hormone acts along the PPARγ-FSP27 axis to stimulate lipolysis in human adipocytes

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Growth hormone acts along the PPARγ-FSP27 axis to stimulate lipolysis in human adipocytes. / Sharma, Vishva M.; Vestergaard, Esben Thyssen; Jessen, Niels; Kolind-Thomsen, Peter; Nellemann, Birgitte; Nielsen, Thomas S.; Vendelbo, Mikkel Holm; Møller, Niels; Sharma, Rita; Lee, Kevin Y.; Kopchick, John J.; Jørgensen, Jens Otto Lunde; Puri, Vishwajeet.

In: American Journal of Physiology: Endocrinology and Metabolism, Vol. 316, No. 1, 2019, p. E34-E42.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Sharma, VM, Vestergaard, ET, Jessen, N, Kolind-Thomsen, P, Nellemann, B, Nielsen, TS, Vendelbo, MH, Møller, N, Sharma, R, Lee, KY, Kopchick, JJ, Jørgensen, JOL & Puri, V 2019, 'Growth hormone acts along the PPARγ-FSP27 axis to stimulate lipolysis in human adipocytes', American Journal of Physiology: Endocrinology and Metabolism, vol. 316, no. 1, pp. E34-E42. https://doi.org/10.1152/ajpendo.00129.2018

APA

Sharma, V. M., Vestergaard, E. T., Jessen, N., Kolind-Thomsen, P., Nellemann, B., Nielsen, T. S., Vendelbo, M. H., Møller, N., Sharma, R., Lee, K. Y., Kopchick, J. J., Jørgensen, J. O. L., & Puri, V. (2019). Growth hormone acts along the PPARγ-FSP27 axis to stimulate lipolysis in human adipocytes. American Journal of Physiology: Endocrinology and Metabolism, 316(1), E34-E42. https://doi.org/10.1152/ajpendo.00129.2018

Vancouver

Sharma VM, Vestergaard ET, Jessen N, Kolind-Thomsen P, Nellemann B, Nielsen TS et al. Growth hormone acts along the PPARγ-FSP27 axis to stimulate lipolysis in human adipocytes. American Journal of Physiology: Endocrinology and Metabolism. 2019;316(1):E34-E42. https://doi.org/10.1152/ajpendo.00129.2018

Author

Sharma, Vishva M. ; Vestergaard, Esben Thyssen ; Jessen, Niels ; Kolind-Thomsen, Peter ; Nellemann, Birgitte ; Nielsen, Thomas S. ; Vendelbo, Mikkel Holm ; Møller, Niels ; Sharma, Rita ; Lee, Kevin Y. ; Kopchick, John J. ; Jørgensen, Jens Otto Lunde ; Puri, Vishwajeet. / Growth hormone acts along the PPARγ-FSP27 axis to stimulate lipolysis in human adipocytes. In: American Journal of Physiology: Endocrinology and Metabolism. 2019 ; Vol. 316, No. 1. pp. E34-E42.

Bibtex

@article{524a3dc36eb1410e8e5cf88917d1803a,
title = "Growth hormone acts along the PPARγ-FSP27 axis to stimulate lipolysis in human adipocytes",
abstract = "The lipolytic effects of growth hormone (GH) have been known for half a century and play an important physiological role for substrate metabolism during fasting. In addition, sustained GH-induced lipolysis is causally linked to insulin resistance. However, the underlying molecular mechanisms remain elusive. In the present study, we obtained experimental data in human subjects and used human adipose-derived stromal vascular cells (hADSCs) as a model system to elucidate GH-triggered molecular signaling that stimulates adipose tissue lipolysis and insulin resistance in human adipocytes. We discovered that GH downregulates the expression of fat-specific protein (FSP27), a negative regulator of lipolysis, by impairing the transcriptional ability of the master transcriptional regulator, peroxisome proliferator-activated receptor-γ (PPARγ) via MEK/ERK activation. Ultimately, GH treatment promotes phosphorylation of PPARγ at Ser273 and causes its translocation from nucleus to the cytosol. Surprisingly, FSP27 overexpression inhibited PPARγ Ser273 phosphorylation and promoted its nuclear retention. GH antagonist treatment had similar effects. Our study identifies a novel signaling mechanism by which GH transcriptionally induces lipolysis via the MEK/ERK pathway that acts along PPARγ-FSP27 in human adipose tissue.",
keywords = "ATGL, CIDEC, Diabetes, Fat metabolism, Growth hormone, Insulin resistance, Lipase, Lipid droplets, Obesity",
author = "Sharma, {Vishva M.} and Vestergaard, {Esben Thyssen} and Niels Jessen and Peter Kolind-Thomsen and Birgitte Nellemann and Nielsen, {Thomas S.} and Vendelbo, {Mikkel Holm} and Niels M{\o}ller and Rita Sharma and Lee, {Kevin Y.} and Kopchick, {John J.} and J{\o}rgensen, {Jens Otto Lunde} and Vishwajeet Puri",
year = "2019",
doi = "10.1152/ajpendo.00129.2018",
language = "English",
volume = "316",
pages = "E34--E42",
journal = "American Journal of Physiology - Endocrinology and Metabolism",
issn = "0193-1849",
publisher = "American Physiological Society",
number = "1",

}

RIS

TY - JOUR

T1 - Growth hormone acts along the PPARγ-FSP27 axis to stimulate lipolysis in human adipocytes

AU - Sharma, Vishva M.

AU - Vestergaard, Esben Thyssen

AU - Jessen, Niels

AU - Kolind-Thomsen, Peter

AU - Nellemann, Birgitte

AU - Nielsen, Thomas S.

AU - Vendelbo, Mikkel Holm

AU - Møller, Niels

AU - Sharma, Rita

AU - Lee, Kevin Y.

AU - Kopchick, John J.

AU - Jørgensen, Jens Otto Lunde

AU - Puri, Vishwajeet

PY - 2019

Y1 - 2019

N2 - The lipolytic effects of growth hormone (GH) have been known for half a century and play an important physiological role for substrate metabolism during fasting. In addition, sustained GH-induced lipolysis is causally linked to insulin resistance. However, the underlying molecular mechanisms remain elusive. In the present study, we obtained experimental data in human subjects and used human adipose-derived stromal vascular cells (hADSCs) as a model system to elucidate GH-triggered molecular signaling that stimulates adipose tissue lipolysis and insulin resistance in human adipocytes. We discovered that GH downregulates the expression of fat-specific protein (FSP27), a negative regulator of lipolysis, by impairing the transcriptional ability of the master transcriptional regulator, peroxisome proliferator-activated receptor-γ (PPARγ) via MEK/ERK activation. Ultimately, GH treatment promotes phosphorylation of PPARγ at Ser273 and causes its translocation from nucleus to the cytosol. Surprisingly, FSP27 overexpression inhibited PPARγ Ser273 phosphorylation and promoted its nuclear retention. GH antagonist treatment had similar effects. Our study identifies a novel signaling mechanism by which GH transcriptionally induces lipolysis via the MEK/ERK pathway that acts along PPARγ-FSP27 in human adipose tissue.

AB - The lipolytic effects of growth hormone (GH) have been known for half a century and play an important physiological role for substrate metabolism during fasting. In addition, sustained GH-induced lipolysis is causally linked to insulin resistance. However, the underlying molecular mechanisms remain elusive. In the present study, we obtained experimental data in human subjects and used human adipose-derived stromal vascular cells (hADSCs) as a model system to elucidate GH-triggered molecular signaling that stimulates adipose tissue lipolysis and insulin resistance in human adipocytes. We discovered that GH downregulates the expression of fat-specific protein (FSP27), a negative regulator of lipolysis, by impairing the transcriptional ability of the master transcriptional regulator, peroxisome proliferator-activated receptor-γ (PPARγ) via MEK/ERK activation. Ultimately, GH treatment promotes phosphorylation of PPARγ at Ser273 and causes its translocation from nucleus to the cytosol. Surprisingly, FSP27 overexpression inhibited PPARγ Ser273 phosphorylation and promoted its nuclear retention. GH antagonist treatment had similar effects. Our study identifies a novel signaling mechanism by which GH transcriptionally induces lipolysis via the MEK/ERK pathway that acts along PPARγ-FSP27 in human adipose tissue.

KW - ATGL

KW - CIDEC

KW - Diabetes

KW - Fat metabolism

KW - Growth hormone

KW - Insulin resistance

KW - Lipase

KW - Lipid droplets

KW - Obesity

U2 - 10.1152/ajpendo.00129.2018

DO - 10.1152/ajpendo.00129.2018

M3 - Journal article

C2 - 30325658

AN - SCOPUS:85059499963

VL - 316

SP - E34-E42

JO - American Journal of Physiology - Endocrinology and Metabolism

JF - American Journal of Physiology - Endocrinology and Metabolism

SN - 0193-1849

IS - 1

ER -

ID: 213862257