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Overexpression of Foxf2 in adipose tissue is associated with lower levels of IRS1 and decreased glucose uptake in vivo

Westergren, Rickard; Nilsson, Daniel; Heglind, Mikael; Arani, Zahra; Grande, Mats; Cederberg, Anna; Ahrén, Bo LU and Enerback, Sven (2010) In American Journal of Physiology: Endocrinology and Metabolism 298(3). p.548-554
Abstract
Westergren R, Nilsson D, Heglind M, Arani Z, Grande M, Cederberg A, Ahren B, Enerback S. Overexpression of Foxf2 in adipose tissue is associated with lower levels of IRS1 and decreased glucose uptake in vivo. Am J Physiol Endocrinol Metab 298: E548-E554, 2010. First published December 15, 2009; doi:10.1152/ajpendo.00395.2009.-Many members of the forkhead genes family of transcription factors have been implicated as important regulators of metabolism, in particular, glucose homeostasis, e. g., Foxo1, Foxa3, and Foxc2. The purpose of this study was to exploit the possibility that yet unknown members of this gene family play a role in regulating glucose tolerance in adipocytes. We identified Foxf2 in a screen for adipose-expressed forkhead... (More)
Westergren R, Nilsson D, Heglind M, Arani Z, Grande M, Cederberg A, Ahren B, Enerback S. Overexpression of Foxf2 in adipose tissue is associated with lower levels of IRS1 and decreased glucose uptake in vivo. Am J Physiol Endocrinol Metab 298: E548-E554, 2010. First published December 15, 2009; doi:10.1152/ajpendo.00395.2009.-Many members of the forkhead genes family of transcription factors have been implicated as important regulators of metabolism, in particular, glucose homeostasis, e. g., Foxo1, Foxa3, and Foxc2. The purpose of this study was to exploit the possibility that yet unknown members of this gene family play a role in regulating glucose tolerance in adipocytes. We identified Foxf2 in a screen for adipose-expressed forkhead genes. In vivo overexpression of Foxf2 in an adipose tissue-restricted fashion demonstrated that such mice display a significantly induced insulin secretion in response to an intravenous glucose load compared with wild-type littermates. In response to increased Foxf2 expression, insulin receptor substrate 1 (IRS1) mRNA and protein levels are significantly downregulated in adipocytes; however, the ratio of serine vs. tyrosine phosphorylation of IRS1 seems to remain unaffected. Furthermore, adipocytes over-expressing Foxf2 have a significantly lower insulin-mediated glucose uptake compared with wild-type adipocytes. These findings argue that Foxf2 is a previously unrecognized regulator of cellular and systemic whole body glucose tolerance, at least in part, due to lower levels of IRS1. Foxf2 and its downstream target genes can provide new insights with regard to identification of novel therapeutic targets. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
type 2 diabetes, resistance, insulin, insulin signaling, forkhead genes, transcriptional regulation, adipocyte metabolism, glucose uptake
in
American Journal of Physiology: Endocrinology and Metabolism
volume
298
issue
3
pages
548 - 554
publisher
American Physiological Society
external identifiers
  • wos:000274705200018
  • scopus:77349109255
ISSN
1522-1555
DOI
10.1152/ajpendo.00395.2009
language
English
LU publication?
yes
id
703056bc-f4fb-4df3-80a0-4d957d4fab1d (old id 1568702)
date added to LUP
2010-03-17 13:23:13
date last changed
2018-05-29 11:13:30
@article{703056bc-f4fb-4df3-80a0-4d957d4fab1d,
  abstract     = {Westergren R, Nilsson D, Heglind M, Arani Z, Grande M, Cederberg A, Ahren B, Enerback S. Overexpression of Foxf2 in adipose tissue is associated with lower levels of IRS1 and decreased glucose uptake in vivo. Am J Physiol Endocrinol Metab 298: E548-E554, 2010. First published December 15, 2009; doi:10.1152/ajpendo.00395.2009.-Many members of the forkhead genes family of transcription factors have been implicated as important regulators of metabolism, in particular, glucose homeostasis, e. g., Foxo1, Foxa3, and Foxc2. The purpose of this study was to exploit the possibility that yet unknown members of this gene family play a role in regulating glucose tolerance in adipocytes. We identified Foxf2 in a screen for adipose-expressed forkhead genes. In vivo overexpression of Foxf2 in an adipose tissue-restricted fashion demonstrated that such mice display a significantly induced insulin secretion in response to an intravenous glucose load compared with wild-type littermates. In response to increased Foxf2 expression, insulin receptor substrate 1 (IRS1) mRNA and protein levels are significantly downregulated in adipocytes; however, the ratio of serine vs. tyrosine phosphorylation of IRS1 seems to remain unaffected. Furthermore, adipocytes over-expressing Foxf2 have a significantly lower insulin-mediated glucose uptake compared with wild-type adipocytes. These findings argue that Foxf2 is a previously unrecognized regulator of cellular and systemic whole body glucose tolerance, at least in part, due to lower levels of IRS1. Foxf2 and its downstream target genes can provide new insights with regard to identification of novel therapeutic targets.},
  author       = {Westergren, Rickard and Nilsson, Daniel and Heglind, Mikael and Arani, Zahra and Grande, Mats and Cederberg, Anna and Ahrén, Bo and Enerback, Sven},
  issn         = {1522-1555},
  keyword      = {type 2 diabetes,resistance,insulin,insulin signaling,forkhead genes,transcriptional regulation,adipocyte metabolism,glucose uptake},
  language     = {eng},
  number       = {3},
  pages        = {548--554},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology: Endocrinology and Metabolism},
  title        = {Overexpression of Foxf2 in adipose tissue is associated with lower levels of IRS1 and decreased glucose uptake in vivo},
  url          = {http://dx.doi.org/10.1152/ajpendo.00395.2009},
  volume       = {298},
  year         = {2010},
}