Oncostatin M is produced in adipose tissue and is regulated in conditions of obesity and type 2 diabetes

David Sanchez-Infantes, Ursula A. White, Carrie M. Elks, Ron F. Morrison, Jeffrey M. Gimble, Robert Considine, Anthony W. Ferrante, Eric Ravussin, Jacqueline M. Stephens

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Context: Adipose tissue is a highly active endocrine organ that secretes many factors that affect other tissues and whole-body metabolism. Adipocytes are responsive to several glycoprotein 130 (gp130) cytokines, some of which have been targeted as potential antiobesity therapeutics. Objective: Oncostatin M (OSM) is a gp130 family member known to inhibit adipocyte differentiation in vitro, but its effects on other adipocyte properties are not characterized. The expression of OSM in white adipose tissue (WAT) has not been evaluated in the context of obesity. Thus, our objective was to examine the expression of adipose tissue OSM in obese animals and humans. Design: OSM expression was examined in adipose tissues from mice with diet-induced and genetic obesity and in obese humans as well as in fractionated adipose tissue from mice. Murine adipocytes were used to examine OSM receptor expression and the effects of OSM on adipocytes, including the secretion of factors such as plasminogen activator inhibitor 1 and IL-6, which are implicated in metabolic diseases. Results: OSM expression is increased in rodent and human obesity/type 2 diabetes mellitus. In humans, OSM levels correlate with body weight and insulin and are inversely correlated with glucose disposal rate as measured by hyperinsulinemic-euglycemic clamp. OSM is not produced from the adipocytes in WAT but derives from cells in the stromovascular fraction, including F4/80+ macrophages. The specific receptor of OSM, OSM receptor-β, is expressed in adipocytes and adipose tissue and increased in both rodent models of obesity examined. OSM acts on adipocytes to induce the expression and secretion of plasminogen activator inhibitor 1 and IL-6. Conclusions: These data indicate that WAT macrophages are a source of OSM and that OSM levels are significantly induced in murine and human obesity/type 2 diabetes mellitus. These studies suggest that OSM produced from immune cells in WAT acts in a paracrine manner on adipocytes to promote a proinflammatory phenotype in adipose tissue.

Original languageEnglish
JournalJournal of Clinical Endocrinology and Metabolism
Volume99
Issue number2
DOIs
StatePublished - Feb 2014

Fingerprint

Oncostatin M
Medical problems
Type 2 Diabetes Mellitus
Adipose Tissue
Adipocytes
Obesity
Tissue
Oncostatin M Receptors
White Adipose Tissue
Macrophages
Plasminogen Activator Inhibitor 1
Rodentia
Interleukin-6
Glycoproteins
Glucose Clamp Technique
Metabolic Diseases
Clamping devices
Nutrition
Metabolism
Animals

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Oncostatin M is produced in adipose tissue and is regulated in conditions of obesity and type 2 diabetes. / Sanchez-Infantes, David; White, Ursula A.; Elks, Carrie M.; Morrison, Ron F.; Gimble, Jeffrey M.; Considine, Robert; Ferrante, Anthony W.; Ravussin, Eric; Stephens, Jacqueline M.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 99, No. 2, 02.2014.

Research output: Contribution to journalArticle

Sanchez-Infantes, D, White, UA, Elks, CM, Morrison, RF, Gimble, JM, Considine, R, Ferrante, AW, Ravussin, E & Stephens, JM 2014, 'Oncostatin M is produced in adipose tissue and is regulated in conditions of obesity and type 2 diabetes', Journal of Clinical Endocrinology and Metabolism, vol. 99, no. 2. https://doi.org/10.1210/jc.2013-3555
Sanchez-Infantes, David ; White, Ursula A. ; Elks, Carrie M. ; Morrison, Ron F. ; Gimble, Jeffrey M. ; Considine, Robert ; Ferrante, Anthony W. ; Ravussin, Eric ; Stephens, Jacqueline M. / Oncostatin M is produced in adipose tissue and is regulated in conditions of obesity and type 2 diabetes. In: Journal of Clinical Endocrinology and Metabolism. 2014 ; Vol. 99, No. 2.
@article{d597272deb98440c825315dc3c063adc,
title = "Oncostatin M is produced in adipose tissue and is regulated in conditions of obesity and type 2 diabetes",
abstract = "Context: Adipose tissue is a highly active endocrine organ that secretes many factors that affect other tissues and whole-body metabolism. Adipocytes are responsive to several glycoprotein 130 (gp130) cytokines, some of which have been targeted as potential antiobesity therapeutics. Objective: Oncostatin M (OSM) is a gp130 family member known to inhibit adipocyte differentiation in vitro, but its effects on other adipocyte properties are not characterized. The expression of OSM in white adipose tissue (WAT) has not been evaluated in the context of obesity. Thus, our objective was to examine the expression of adipose tissue OSM in obese animals and humans. Design: OSM expression was examined in adipose tissues from mice with diet-induced and genetic obesity and in obese humans as well as in fractionated adipose tissue from mice. Murine adipocytes were used to examine OSM receptor expression and the effects of OSM on adipocytes, including the secretion of factors such as plasminogen activator inhibitor 1 and IL-6, which are implicated in metabolic diseases. Results: OSM expression is increased in rodent and human obesity/type 2 diabetes mellitus. In humans, OSM levels correlate with body weight and insulin and are inversely correlated with glucose disposal rate as measured by hyperinsulinemic-euglycemic clamp. OSM is not produced from the adipocytes in WAT but derives from cells in the stromovascular fraction, including F4/80+ macrophages. The specific receptor of OSM, OSM receptor-β, is expressed in adipocytes and adipose tissue and increased in both rodent models of obesity examined. OSM acts on adipocytes to induce the expression and secretion of plasminogen activator inhibitor 1 and IL-6. Conclusions: These data indicate that WAT macrophages are a source of OSM and that OSM levels are significantly induced in murine and human obesity/type 2 diabetes mellitus. These studies suggest that OSM produced from immune cells in WAT acts in a paracrine manner on adipocytes to promote a proinflammatory phenotype in adipose tissue.",
author = "David Sanchez-Infantes and White, {Ursula A.} and Elks, {Carrie M.} and Morrison, {Ron F.} and Gimble, {Jeffrey M.} and Robert Considine and Ferrante, {Anthony W.} and Eric Ravussin and Stephens, {Jacqueline M.}",
year = "2014",
month = "2",
doi = "10.1210/jc.2013-3555",
language = "English",
volume = "99",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "2",

}

TY - JOUR

T1 - Oncostatin M is produced in adipose tissue and is regulated in conditions of obesity and type 2 diabetes

AU - Sanchez-Infantes, David

AU - White, Ursula A.

AU - Elks, Carrie M.

AU - Morrison, Ron F.

AU - Gimble, Jeffrey M.

AU - Considine, Robert

AU - Ferrante, Anthony W.

AU - Ravussin, Eric

AU - Stephens, Jacqueline M.

PY - 2014/2

Y1 - 2014/2

N2 - Context: Adipose tissue is a highly active endocrine organ that secretes many factors that affect other tissues and whole-body metabolism. Adipocytes are responsive to several glycoprotein 130 (gp130) cytokines, some of which have been targeted as potential antiobesity therapeutics. Objective: Oncostatin M (OSM) is a gp130 family member known to inhibit adipocyte differentiation in vitro, but its effects on other adipocyte properties are not characterized. The expression of OSM in white adipose tissue (WAT) has not been evaluated in the context of obesity. Thus, our objective was to examine the expression of adipose tissue OSM in obese animals and humans. Design: OSM expression was examined in adipose tissues from mice with diet-induced and genetic obesity and in obese humans as well as in fractionated adipose tissue from mice. Murine adipocytes were used to examine OSM receptor expression and the effects of OSM on adipocytes, including the secretion of factors such as plasminogen activator inhibitor 1 and IL-6, which are implicated in metabolic diseases. Results: OSM expression is increased in rodent and human obesity/type 2 diabetes mellitus. In humans, OSM levels correlate with body weight and insulin and are inversely correlated with glucose disposal rate as measured by hyperinsulinemic-euglycemic clamp. OSM is not produced from the adipocytes in WAT but derives from cells in the stromovascular fraction, including F4/80+ macrophages. The specific receptor of OSM, OSM receptor-β, is expressed in adipocytes and adipose tissue and increased in both rodent models of obesity examined. OSM acts on adipocytes to induce the expression and secretion of plasminogen activator inhibitor 1 and IL-6. Conclusions: These data indicate that WAT macrophages are a source of OSM and that OSM levels are significantly induced in murine and human obesity/type 2 diabetes mellitus. These studies suggest that OSM produced from immune cells in WAT acts in a paracrine manner on adipocytes to promote a proinflammatory phenotype in adipose tissue.

AB - Context: Adipose tissue is a highly active endocrine organ that secretes many factors that affect other tissues and whole-body metabolism. Adipocytes are responsive to several glycoprotein 130 (gp130) cytokines, some of which have been targeted as potential antiobesity therapeutics. Objective: Oncostatin M (OSM) is a gp130 family member known to inhibit adipocyte differentiation in vitro, but its effects on other adipocyte properties are not characterized. The expression of OSM in white adipose tissue (WAT) has not been evaluated in the context of obesity. Thus, our objective was to examine the expression of adipose tissue OSM in obese animals and humans. Design: OSM expression was examined in adipose tissues from mice with diet-induced and genetic obesity and in obese humans as well as in fractionated adipose tissue from mice. Murine adipocytes were used to examine OSM receptor expression and the effects of OSM on adipocytes, including the secretion of factors such as plasminogen activator inhibitor 1 and IL-6, which are implicated in metabolic diseases. Results: OSM expression is increased in rodent and human obesity/type 2 diabetes mellitus. In humans, OSM levels correlate with body weight and insulin and are inversely correlated with glucose disposal rate as measured by hyperinsulinemic-euglycemic clamp. OSM is not produced from the adipocytes in WAT but derives from cells in the stromovascular fraction, including F4/80+ macrophages. The specific receptor of OSM, OSM receptor-β, is expressed in adipocytes and adipose tissue and increased in both rodent models of obesity examined. OSM acts on adipocytes to induce the expression and secretion of plasminogen activator inhibitor 1 and IL-6. Conclusions: These data indicate that WAT macrophages are a source of OSM and that OSM levels are significantly induced in murine and human obesity/type 2 diabetes mellitus. These studies suggest that OSM produced from immune cells in WAT acts in a paracrine manner on adipocytes to promote a proinflammatory phenotype in adipose tissue.

UR - http://www.scopus.com/inward/record.url?scp=84893801143&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84893801143&partnerID=8YFLogxK

U2 - 10.1210/jc.2013-3555

DO - 10.1210/jc.2013-3555

M3 - Article

C2 - 24297795

AN - SCOPUS:84893801143

VL - 99

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 2

ER -