Regulation of brown fat adipogenesis by protein tyrosine phosphatase 1B

Kosuke Matsuo, Ahmed Bettaieb, Naoto Nagata, Izumi Matsuo, Heike Keilhack, Fawaz Haj

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25 Scopus citations

Abstract

Background: Protein-tyrosine phosphatase 1B (PTP1B) is a physiological regulator of insulin signaling and energy balance, but its role in brown fat adipogenesis requires additional investigation. Methodology/Principal Findings: To precisely determine the role of PTP1B in adipogenesis, we established preadipocyte cell lines from wild type and PTP1B knockout (KO) mice. In addition, we reconstituted KO cells with wild type, substratetrapping (D/A) and sumoylation-resistant (K/R) PTP1B mutants, then characterized differentiation and signaling in these cells. KO, D/A- and WT-reconstituted cells fully differentiated into mature adipocytes with KO and D/A cells exhibiting a trend for enhanced differentiation. In contrast, K/R cells exhibited marked attenuation in differentiation and lipid accumulation compared with WT cells. Expression of adipogenic markers PPARγ, C/EBPα, C/EBPδ, and PGC1α mirrored the differentiation pattern. In addition, the differentiation deficit in K/R cells could be reversed completely by the PPARγ activator troglitazone. PTP1B deficiency enhanced insulin receptor (IR) and insulin receptor substrate 1 (IRS1) tyrosyl phosphorylation, while K/R cells exhibited attenuated insulin-induced IR and IRS1 phosphorylation and glucose uptake compared with WT cells. In addition, substrate-trapping studies revealed that IRS1 is a substrate for PTP1B in brown adipocytes. Moreover, KO, D/A and K/R cells exhibited elevated AMPK and ACC phosphorylation compared with WT cells. Conclusions: These data indicate that PTP1B is a modulator of brown fat adipogenesis and suggest that adipocyte differentiation requires regulated expression of PTP1B.

Original languageEnglish (US)
Article numbere16446
JournalPLoS One
Volume6
Issue number1
DOIs
StatePublished - 2011

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Matsuo, K., Bettaieb, A., Nagata, N., Matsuo, I., Keilhack, H., & Haj, F. (2011). Regulation of brown fat adipogenesis by protein tyrosine phosphatase 1B. PLoS One, 6(1), [e16446]. https://doi.org/10.1371/journal.pone.0016446