Abstract
Despite extensive studies implicating tumor necrosis factor (TNF)-α as a contributing cause of insulin resistance, the mechanism(s) by which TNF-α alters energy metabolism in vivo and the tissue specificity of TNF-α action are unclear. Here, we investigated the effects of TNF-α infusion on gene expression and energy metabolism in adult rats. A 1-day TNF-α treatment decreased overall insulin sensitivity and caused a 70% increase (P = 0.005) in plasma levels of free fatty acids (FFAs) and a 46% decrease (P = 0.01) in ACRP30. A 4-day TNF-α infusion caused insulin resistance and significant elevation of plasma levels of FFAs and triglycerides and reduction of ACRP30. Plasma glucose concentration was not altered following TNF-α infusion for up to 4 days. As revealed by oligonucleotide microarrays, TNF-α evoked major and rapid changes in adipocyte gene expression, favoring FFA release and cytokine production, and fewer changes in liver gene expression, but favoring FFA and cholesterol synthesis and VLDL production. There was only a moderate repressive effect on skeletal muscle gene expression. We demonstrate that TNF-α antagonizes the actions of insulin, at least in part, through regulation of adipocyte gene expression including reduction in ACRP30 mRNA and induction of lipolysis resulting in increased plasma FFAs. TNF-α later alters systemic energy homeostasis that closely resembles the insulin resistance phenotype. Our data suggest that blockade of TNF-α action in adipose tissue may prevent TNF-α-induced insulin resistance in vivo.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3176-3188 |
| Number of pages | 13 |
| Journal | Diabetes |
| Volume | 51 |
| Issue number | 11 |
| State | Published - Nov 1 2002 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism
Cite this
Profiling gene transcription in vivo reveals adipose tissue as an immediate target of tumor necrosis factor-α : Implications for insulin resistance. / Ruan, Hong; Miles, Philip D G; Ladd-Acosta, Christine Marie; Ross, Kenneth; Golub, Todd R.; Olefsky, Jerrold M.; Lodish, Harvey F.
In: Diabetes, Vol. 51, No. 11, 01.11.2002, p. 3176-3188.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Profiling gene transcription in vivo reveals adipose tissue as an immediate target of tumor necrosis factor-α
T2 - Implications for insulin resistance
AU - Ruan, Hong
AU - Miles, Philip D G
AU - Ladd-Acosta, Christine Marie
AU - Ross, Kenneth
AU - Golub, Todd R.
AU - Olefsky, Jerrold M.
AU - Lodish, Harvey F.
PY - 2002/11/1
Y1 - 2002/11/1
N2 - Despite extensive studies implicating tumor necrosis factor (TNF)-α as a contributing cause of insulin resistance, the mechanism(s) by which TNF-α alters energy metabolism in vivo and the tissue specificity of TNF-α action are unclear. Here, we investigated the effects of TNF-α infusion on gene expression and energy metabolism in adult rats. A 1-day TNF-α treatment decreased overall insulin sensitivity and caused a 70% increase (P = 0.005) in plasma levels of free fatty acids (FFAs) and a 46% decrease (P = 0.01) in ACRP30. A 4-day TNF-α infusion caused insulin resistance and significant elevation of plasma levels of FFAs and triglycerides and reduction of ACRP30. Plasma glucose concentration was not altered following TNF-α infusion for up to 4 days. As revealed by oligonucleotide microarrays, TNF-α evoked major and rapid changes in adipocyte gene expression, favoring FFA release and cytokine production, and fewer changes in liver gene expression, but favoring FFA and cholesterol synthesis and VLDL production. There was only a moderate repressive effect on skeletal muscle gene expression. We demonstrate that TNF-α antagonizes the actions of insulin, at least in part, through regulation of adipocyte gene expression including reduction in ACRP30 mRNA and induction of lipolysis resulting in increased plasma FFAs. TNF-α later alters systemic energy homeostasis that closely resembles the insulin resistance phenotype. Our data suggest that blockade of TNF-α action in adipose tissue may prevent TNF-α-induced insulin resistance in vivo.
AB - Despite extensive studies implicating tumor necrosis factor (TNF)-α as a contributing cause of insulin resistance, the mechanism(s) by which TNF-α alters energy metabolism in vivo and the tissue specificity of TNF-α action are unclear. Here, we investigated the effects of TNF-α infusion on gene expression and energy metabolism in adult rats. A 1-day TNF-α treatment decreased overall insulin sensitivity and caused a 70% increase (P = 0.005) in plasma levels of free fatty acids (FFAs) and a 46% decrease (P = 0.01) in ACRP30. A 4-day TNF-α infusion caused insulin resistance and significant elevation of plasma levels of FFAs and triglycerides and reduction of ACRP30. Plasma glucose concentration was not altered following TNF-α infusion for up to 4 days. As revealed by oligonucleotide microarrays, TNF-α evoked major and rapid changes in adipocyte gene expression, favoring FFA release and cytokine production, and fewer changes in liver gene expression, but favoring FFA and cholesterol synthesis and VLDL production. There was only a moderate repressive effect on skeletal muscle gene expression. We demonstrate that TNF-α antagonizes the actions of insulin, at least in part, through regulation of adipocyte gene expression including reduction in ACRP30 mRNA and induction of lipolysis resulting in increased plasma FFAs. TNF-α later alters systemic energy homeostasis that closely resembles the insulin resistance phenotype. Our data suggest that blockade of TNF-α action in adipose tissue may prevent TNF-α-induced insulin resistance in vivo.
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UR - http://www.scopus.com/inward/citedby.url?scp=0036828912&partnerID=8YFLogxK
M3 - Article
C2 - 12401708
AN - SCOPUS:0036828912
VL - 51
SP - 3176
EP - 3188
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 11
ER -