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
Human and Animal Cells 293(RCB1637)