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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 ; Grände, Mats ; Cederberg, Anna ; Ahrén, Bo ; Enerbäck, Sven

American journal of physiology: endocrinology and metabolism, 2010-03, Vol.298 (3), p.E548-E554 [Periódico revisado por pares]

United States: American Physiological Society

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Título:
Overexpression of Foxf2 in adipose tissue is associated with lower levels of IRS1 and decreased glucose uptake in vivo
Autor: Westergren, Rickard ; Nilsson, Daniel ; Heglind, Mikael ; Arani, Zahra ; Grände, Mats ; Cederberg, Anna ; Ahrén, Bo ; Enerbäck, Sven
Assuntos: 3T3 Cells ; adipocyte metabolism ; Adipocytes ; Adipose Tissue ; Adipose Tissue - metabolism ; Animals ; Basic Medicine ; Cell and Molecular Biology ; Cell- och molekylärbiologi ; Down-Regulation ; forkhead genes ; Forkhead Transcription Factors ; Forkhead Transcription Factors - metabolism ; Fysiologi ; Gene Expression ; genetics ; Glucose ; Glucose - metabolism ; glucose uptake ; Homeostasis ; Homeostasis - genetics ; Humans ; Inbred C57BL ; Insulin ; Insulin Receptor Substrate Proteins ; Insulin Receptor Substrate Proteins - metabolism ; insulin signaling ; Medical and Health Sciences ; Medicin och hälsovetenskap ; Medicinska och farmaceutiska grundvetenskaper ; Metabolism ; Mice ; Mice, Inbred C57BL ; Physiology ; resistance ; Tissues ; transcriptional regulation ; type 2 diabetes
É parte de: American journal of physiology: endocrinology and metabolism, 2010-03, Vol.298 (3), p.E548-E554
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: 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 overexpressing 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.
Editor: United States: American Physiological Society
Idioma: Inglês

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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 ; Grände, Mats ; Cederberg, Anna ; Ahrén, Bo ; Enerbäck, Sven

United States: American Physiological Society

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