SIK2 is critical in the regulation of lipid homeostasis and adipogenesis in vivo

Jinyoung Park, Young Sil Yoon, Hye Sook Han, Yong Hoon Kim, Yoshihiro Ogawa, Keun Gyu Park, Chul Ho Lee, Seong Tae Kim, Seung-Hoi Koo

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Cyclic AMP promotes chronic expression of target genes mainly by protein kinase A-dependent activation of CREB transcription factor machineries in the metabolic tissues. Here, we wanted to elaborate whether CREB-regulated transcription factor (CRTC)2 and its negative regulator salt-inducible kinase (SIK)2 are involved in the transcriptional control of the metabolic pathway in adipocytes. SIK2 knockout (SIK2 KO) mice exhibited higher blood glucose levels that were associated with impaired glucose and insulin tolerance. Hypertriglyceridemia was apparent in SIK2 KO mice, mainly due to the increased lipolysis from white adipocytes and the decreased fatty acid uptake in the peripheral tissues. Investigation of white adipocytes revealed the increases in fat cell size and macrophage infiltration, which could be linked to the metabolic anomaly that is associated in these mice. Interestingly, SIK2 KO promoted the enhancement in the CRTC2-CREB transcriptional pathway in white adipocytes. SIK2 KO mice displayed increased expression of activating transcription factor (ATF)3 and subsequent downregulation of GLUT4 expression and reduction in high-molecular weight adiponectin levels in the plasma, leading to the reduced glucose uptake in the muscle and white adipocytes. The effect of SIK2-dependent regulation of adipocyte metabolism was further confirmed by in vitro cell cultures of 3T3 L1 adipocytes and the differentiated preadipocytes from the SIK2 or CRTC2 KO mice. Collectively, these data suggest that SIK2 is critical in regulating whole-body glucose metabolism primarily by controlling the CRTC2-CREB function of the white adipocytes.

Original languageEnglish
Pages (from-to)3659-3673
Number of pages15
JournalDiabetes
Volume63
Issue number11
DOIs
Publication statusPublished - 2014 Jan 1

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White Adipocytes
Adipogenesis
Homeostasis
Adipocytes
Lipids
Knockout Mice
Activating Transcription Factor 3
Transcription Factors
Glucose
Glucose Intolerance
Hypertriglyceridemia
Lipolysis
Adiponectin
Cyclic AMP-Dependent Protein Kinases
Metabolic Networks and Pathways
Cell Size
Cyclic AMP
Blood Glucose
Phosphotransferases
Fatty Acids

Cite this

Park, J., Yoon, Y. S., Han, H. S., Kim, Y. H., Ogawa, Y., Park, K. G., ... Koo, S-H. (2014). SIK2 is critical in the regulation of lipid homeostasis and adipogenesis in vivo. Diabetes, 63(11), 3659-3673. https://doi.org/10.2337/db13-1423

SIK2 is critical in the regulation of lipid homeostasis and adipogenesis in vivo. / Park, Jinyoung; Yoon, Young Sil; Han, Hye Sook; Kim, Yong Hoon; Ogawa, Yoshihiro; Park, Keun Gyu; Lee, Chul Ho; Kim, Seong Tae; Koo, Seung-Hoi.

In: Diabetes, Vol. 63, No. 11, 01.01.2014, p. 3659-3673.

Research output: Contribution to journalArticle

Park, J, Yoon, YS, Han, HS, Kim, YH, Ogawa, Y, Park, KG, Lee, CH, Kim, ST & Koo, S-H 2014, 'SIK2 is critical in the regulation of lipid homeostasis and adipogenesis in vivo', Diabetes, vol. 63, no. 11, pp. 3659-3673. https://doi.org/10.2337/db13-1423
Park J, Yoon YS, Han HS, Kim YH, Ogawa Y, Park KG et al. SIK2 is critical in the regulation of lipid homeostasis and adipogenesis in vivo. Diabetes. 2014 Jan 1;63(11):3659-3673. https://doi.org/10.2337/db13-1423
Park, Jinyoung ; Yoon, Young Sil ; Han, Hye Sook ; Kim, Yong Hoon ; Ogawa, Yoshihiro ; Park, Keun Gyu ; Lee, Chul Ho ; Kim, Seong Tae ; Koo, Seung-Hoi. / SIK2 is critical in the regulation of lipid homeostasis and adipogenesis in vivo. In: Diabetes. 2014 ; Vol. 63, No. 11. pp. 3659-3673.
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