ASK1 signalling regulates brown and beige adipocyte function

Kazuki Hattori; Isao Naguro; Kohki Okabe; Takashi Funatsu; Shotaro Furutani; Kohsuke Takeda; Hidenori Ichijo

doi:10.1038/ncomms11158

ASK1 signalling regulates brown and beige adipocyte function

Nat Commun. 2016 Apr 5:7:11158. doi: 10.1038/ncomms11158.

Authors

Kazuki Hattori¹, Isao Naguro¹, Kohki Okabe^{2

3}, Takashi Funatsu², Shotaro Furutani¹, Kohsuke Takeda⁴, Hidenori Ichijo¹

Affiliations

¹ The laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
² The laboratory of Bioanalytical Chemistry, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
³ JST, PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
⁴ Division of Cell Regulation, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.

Abstract

Recent studies suggest that adult humans have active brown or beige adipocytes, the activation of which might be a therapeutic strategy for the treatment of diverse metabolic diseases. Here we show that the protein kinase ASK1 regulates brown and beige adipocytes function. In brown or white adipocytes, the PKA-ASK1-p38 axis is activated in response to cAMP signalling and contributes to the cell-autonomous induction of genes, including Ucp1. Global and fat-specific ASK1 deficiency leads to impaired metabolic responses, including thermogenesis and oxygen consumption, at the cell and whole-body levels, respectively. Our data thus indicate that the ASK1 signalling axis is a regulator of brown and beige adipocyte gene expression and function.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3T3-L1 Cells
Adipocytes, Brown / cytology
Adipocytes, Brown / metabolism*
Adipocytes, White / cytology
Adipocytes, White / metabolism
Adipose Tissue, Brown / cytology
Adipose Tissue, Brown / metabolism*
Adipose Tissue, White / cytology
Adipose Tissue, White / metabolism
Animals
Cell Differentiation
Cyclic AMP / metabolism
Cyclic AMP-Dependent Protein Kinases / genetics
Cyclic AMP-Dependent Protein Kinases / metabolism
Female
Gene Expression Regulation
HEK293 Cells
Humans
Ion Channels / genetics
Ion Channels / metabolism
MAP Kinase Kinase Kinase 5 / genetics
MAP Kinase Kinase Kinase 5 / metabolism*
Male
Mice
Mice, Inbred C57BL
Mitochondrial Proteins / genetics
Mitochondrial Proteins / metabolism
Oxygen Consumption / genetics
Signal Transduction*
Thermogenesis / genetics*
Uncoupling Protein 1
p38 Mitogen-Activated Protein Kinases / genetics
p38 Mitogen-Activated Protein Kinases / metabolism

Substances

Ion Channels
Mitochondrial Proteins
UCP1 protein, human
Ucp1 protein, mouse
Uncoupling Protein 1
Cyclic AMP
Cyclic AMP-Dependent Protein Kinases
p38 Mitogen-Activated Protein Kinases
MAP Kinase Kinase Kinase 5
MAP3K5 protein, human