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 language | English (US) |
|---|---|
| Article number | e16446 |
| Journal | PLoS One |
| Volume | 6 |
| Issue number | 1 |
| DOIs | |
| State | Published - 2011 |
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ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Medicine(all)
Cite this
Regulation of brown fat adipogenesis by protein tyrosine phosphatase 1B. / Matsuo, Kosuke; Bettaieb, Ahmed; Nagata, Naoto; Matsuo, Izumi; Keilhack, Heike; Haj, Fawaz.
In: PLoS One, Vol. 6, No. 1, e16446, 2011.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Regulation of brown fat adipogenesis by protein tyrosine phosphatase 1B
AU - Matsuo, Kosuke
AU - Bettaieb, Ahmed
AU - Nagata, Naoto
AU - Matsuo, Izumi
AU - Keilhack, Heike
AU - Haj, Fawaz
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79551639002&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79551639002&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0016446
DO - 10.1371/journal.pone.0016446
M3 - Article
C2 - 21305007
AN - SCOPUS:79551639002
VL - 6
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 1
M1 - e16446
ER -