| RRC ID |
72869
|
| Author |
Sakaguchi M, Okagawa S, Okubo Y, Otsuka Y, Fukuda K, Igata M, Kondo T, Sato Y, Yoshizawa T, Fukuda T, Yamagata K, Cai W, Tseng YH, Sakaguchi N, Kahn CR, Araki E.
|
| Title |
Phosphatase protector alpha4 (α4) is involved in adipocyte maintenance and mitochondrial homeostasis through regulation of insulin signaling.
|
| Journal |
Nat Commun
|
| Abstract |
Insulin signaling is mediated via a network of protein phosphorylation. Dysregulation of this network is central to obesity, type 2 diabetes and metabolic syndrome. Here we investigate the role of phosphatase binding protein Alpha4 (α4) that is essential for the serine/threonine protein phosphatase 2A (PP2A) in insulin action/resistance in adipocytes. Unexpectedly, adipocyte-specific inactivation of α4 impairs insulin-induced Akt-mediated serine/threonine phosphorylation despite a decrease in the protein phosphatase 2A (PP2A) levels. Interestingly, loss of α4 also reduces insulin-induced insulin receptor tyrosine phosphorylation. This occurs through decreased association of α4 with Y-box protein 1, resulting in the enhancement of the tyrosine phosphatase protein tyrosine phosphatase 1B (PTP1B) expression. Moreover, adipocyte-specific knockout of α4 in male mice results in impaired adipogenesis and altered mitochondrial oxidation leading to increased inflammation, systemic insulin resistance, hepatosteatosis, islet hyperplasia, and impaired thermogenesis. Thus, the α4 /Y-box protein 1(YBX1)-mediated pathway of insulin receptor signaling is involved in maintaining insulin sensitivity, normal adipose tissue homeostasis and systemic metabolism.
|
| Volume |
13(1)
|
| Pages |
6092
|
| Published |
2022-10-14
|
| DOI |
10.1038/s41467-022-33842-4
|
| PII |
10.1038/s41467-022-33842-4
|
| PMID |
36241662
|
| PMC |
PMC9568526
|
| MeSH |
Adipocytes / metabolism
Animals
Diabetes Mellitus, Type 2* / genetics
Diabetes Mellitus, Type 2* / metabolism
Homeostasis
Insulin / metabolism
Insulin Resistance*
Male
Mice
Phosphorylation
Protein Phosphatase 2 / metabolism
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / genetics
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Receptor, Insulin / genetics
Receptor, Insulin / metabolism
Serine / metabolism
Threonine / metabolism
Tyrosine / metabolism
|
| IF |
12.121
|
| Resource |
| Human and Animal Cells |
293(RCB1637) |
