Resistin / Fizz3 Expression in Relation to Obesity and Peroxisome Proliferator - Activated Receptor-γ Action in Humans

David B. Savage, Ciaran P. Sewter, Ellen S. Klenk, David G. Segal, Antonio Vidal-Puig, Robert Considine, Stephen O'Rahilly

Research output: Contribution to journalArticle

641 Citations (Scopus)

Abstract

Recent studies in murine models suggest that resistin (also called Fizz3 [1]), a novel cysteine-rich protein secreted by adipocytes, may represent the long-sought link between obesity and insulin resistance (2). Furthermore, peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists appear to inhibit resistin expression in murine adipocytes, providing a possible explanation for the mode of action of this class of insulin sensitizers (2). Using a fluorescent real-time reverse transcriptase-polymerase chain reaction-based assay, we found that resistin mRNA levels in whole adipose tissue samples were increased in morbidly obese humans compared with lean control subjects. However, in freshly isolated human adipocytes, resistin mRNA levels were very low and showed no correlation with BMI. Resistin mRNA was undetectable in preadipocytes, endothelial cells, and vascular smooth muscle cells, but it was readily detectable in circulating mononuclear cells. Although exposure of human mononuclear cells to PPAR-γ agonists markedly upregulated fatty acid-binding protein-4 expression, these agents had no effect on mononuclear cell resistin expression. Finally, resistin mRNA was undetectable in adipocytes from a severely insulin-resistant subject with a dominant-negative mutation in PPAR-γ (3). We conclude that the recently described relationships of murine resistin/Fizz3 expression with obesity, insulin resistance, and PPAR-γ action may not readily translate to humans. Further studies of this novel class of proteins are needed to clarify their roles in human metabolism.

Original languageEnglish
Pages (from-to)2199-2202
Number of pages4
JournalDiabetes
Volume50
Issue number10
StatePublished - Oct 2001

Fingerprint

Resistin
Peroxisome Proliferator-Activated Receptors
Obesity
Adipocytes
Messenger RNA
Insulin Resistance
Insulin
Fatty Acid-Binding Proteins
Reverse Transcriptase Polymerase Chain Reaction
Vascular Smooth Muscle
Smooth Muscle Myocytes
Cysteine
Adipose Tissue
Real-Time Polymerase Chain Reaction
Proteins
Endothelial Cells
Mutation

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

Savage, D. B., Sewter, C. P., Klenk, E. S., Segal, D. G., Vidal-Puig, A., Considine, R., & O'Rahilly, S. (2001). Resistin / Fizz3 Expression in Relation to Obesity and Peroxisome Proliferator - Activated Receptor-γ Action in Humans. Diabetes, 50(10), 2199-2202.

Resistin / Fizz3 Expression in Relation to Obesity and Peroxisome Proliferator - Activated Receptor-γ Action in Humans. / Savage, David B.; Sewter, Ciaran P.; Klenk, Ellen S.; Segal, David G.; Vidal-Puig, Antonio; Considine, Robert; O'Rahilly, Stephen.

In: Diabetes, Vol. 50, No. 10, 10.2001, p. 2199-2202.

Research output: Contribution to journalArticle

Savage, DB, Sewter, CP, Klenk, ES, Segal, DG, Vidal-Puig, A, Considine, R & O'Rahilly, S 2001, 'Resistin / Fizz3 Expression in Relation to Obesity and Peroxisome Proliferator - Activated Receptor-γ Action in Humans', Diabetes, vol. 50, no. 10, pp. 2199-2202.
Savage, David B. ; Sewter, Ciaran P. ; Klenk, Ellen S. ; Segal, David G. ; Vidal-Puig, Antonio ; Considine, Robert ; O'Rahilly, Stephen. / Resistin / Fizz3 Expression in Relation to Obesity and Peroxisome Proliferator - Activated Receptor-γ Action in Humans. In: Diabetes. 2001 ; Vol. 50, No. 10. pp. 2199-2202.
@article{8b698985fc7e4ead9a732878829158d6,
title = "Resistin / Fizz3 Expression in Relation to Obesity and Peroxisome Proliferator - Activated Receptor-γ Action in Humans",
abstract = "Recent studies in murine models suggest that resistin (also called Fizz3 [1]), a novel cysteine-rich protein secreted by adipocytes, may represent the long-sought link between obesity and insulin resistance (2). Furthermore, peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists appear to inhibit resistin expression in murine adipocytes, providing a possible explanation for the mode of action of this class of insulin sensitizers (2). Using a fluorescent real-time reverse transcriptase-polymerase chain reaction-based assay, we found that resistin mRNA levels in whole adipose tissue samples were increased in morbidly obese humans compared with lean control subjects. However, in freshly isolated human adipocytes, resistin mRNA levels were very low and showed no correlation with BMI. Resistin mRNA was undetectable in preadipocytes, endothelial cells, and vascular smooth muscle cells, but it was readily detectable in circulating mononuclear cells. Although exposure of human mononuclear cells to PPAR-γ agonists markedly upregulated fatty acid-binding protein-4 expression, these agents had no effect on mononuclear cell resistin expression. Finally, resistin mRNA was undetectable in adipocytes from a severely insulin-resistant subject with a dominant-negative mutation in PPAR-γ (3). We conclude that the recently described relationships of murine resistin/Fizz3 expression with obesity, insulin resistance, and PPAR-γ action may not readily translate to humans. Further studies of this novel class of proteins are needed to clarify their roles in human metabolism.",
author = "Savage, {David B.} and Sewter, {Ciaran P.} and Klenk, {Ellen S.} and Segal, {David G.} and Antonio Vidal-Puig and Robert Considine and Stephen O'Rahilly",
year = "2001",
month = "10",
language = "English",
volume = "50",
pages = "2199--2202",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "10",

}

TY - JOUR

T1 - Resistin / Fizz3 Expression in Relation to Obesity and Peroxisome Proliferator - Activated Receptor-γ Action in Humans

AU - Savage, David B.

AU - Sewter, Ciaran P.

AU - Klenk, Ellen S.

AU - Segal, David G.

AU - Vidal-Puig, Antonio

AU - Considine, Robert

AU - O'Rahilly, Stephen

PY - 2001/10

Y1 - 2001/10

N2 - Recent studies in murine models suggest that resistin (also called Fizz3 [1]), a novel cysteine-rich protein secreted by adipocytes, may represent the long-sought link between obesity and insulin resistance (2). Furthermore, peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists appear to inhibit resistin expression in murine adipocytes, providing a possible explanation for the mode of action of this class of insulin sensitizers (2). Using a fluorescent real-time reverse transcriptase-polymerase chain reaction-based assay, we found that resistin mRNA levels in whole adipose tissue samples were increased in morbidly obese humans compared with lean control subjects. However, in freshly isolated human adipocytes, resistin mRNA levels were very low and showed no correlation with BMI. Resistin mRNA was undetectable in preadipocytes, endothelial cells, and vascular smooth muscle cells, but it was readily detectable in circulating mononuclear cells. Although exposure of human mononuclear cells to PPAR-γ agonists markedly upregulated fatty acid-binding protein-4 expression, these agents had no effect on mononuclear cell resistin expression. Finally, resistin mRNA was undetectable in adipocytes from a severely insulin-resistant subject with a dominant-negative mutation in PPAR-γ (3). We conclude that the recently described relationships of murine resistin/Fizz3 expression with obesity, insulin resistance, and PPAR-γ action may not readily translate to humans. Further studies of this novel class of proteins are needed to clarify their roles in human metabolism.

AB - Recent studies in murine models suggest that resistin (also called Fizz3 [1]), a novel cysteine-rich protein secreted by adipocytes, may represent the long-sought link between obesity and insulin resistance (2). Furthermore, peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists appear to inhibit resistin expression in murine adipocytes, providing a possible explanation for the mode of action of this class of insulin sensitizers (2). Using a fluorescent real-time reverse transcriptase-polymerase chain reaction-based assay, we found that resistin mRNA levels in whole adipose tissue samples were increased in morbidly obese humans compared with lean control subjects. However, in freshly isolated human adipocytes, resistin mRNA levels were very low and showed no correlation with BMI. Resistin mRNA was undetectable in preadipocytes, endothelial cells, and vascular smooth muscle cells, but it was readily detectable in circulating mononuclear cells. Although exposure of human mononuclear cells to PPAR-γ agonists markedly upregulated fatty acid-binding protein-4 expression, these agents had no effect on mononuclear cell resistin expression. Finally, resistin mRNA was undetectable in adipocytes from a severely insulin-resistant subject with a dominant-negative mutation in PPAR-γ (3). We conclude that the recently described relationships of murine resistin/Fizz3 expression with obesity, insulin resistance, and PPAR-γ action may not readily translate to humans. Further studies of this novel class of proteins are needed to clarify their roles in human metabolism.

UR - http://www.scopus.com/inward/record.url?scp=0035487109&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035487109&partnerID=8YFLogxK

M3 - Article

VL - 50

SP - 2199

EP - 2202

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 10

ER -