Leptin and amylin act in an additive manner to activate overlapping signaling pathways in peripheral tissues

In vitro and ex vivo studies in humans

Hyun Seuk Moon, John P. Chamberland, Kalliope N. Diakopoulos, Christina G. Fiorenza, Florencia Ziemke, Benjamin Schneider, Christos S. Mantzoros

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

OBJECTIVE - Amylin interacts with leptin to alter metabolism. We evaluated, for the first time, amylin- and/or leptin-activated signaling pathways in human peripheral tissues (hPTs). RESEARCH DESIGN AND METHODS - Leptin and amylin signaling studies were performed in vitro in human primary adipocytes (hPAs) and human peripheral blood mononuclear cells (hPBMCs) and ex vivo in human adipose tissue (hAT) from male versus female subjects, obese versus lean subjects, and subjects with subcutaneous versus omental adipose tissue. RESULTS - The long form of leptin receptor was expressed in human tissues and cells studied in ex vivo and in vitro, respectively. Leptin and amylin alone and in combination activate signal transducer and activator of transcription 3 (STAT3), AMP-activated protein kinase, Akt, and extracellular signal-regulated kinase signaling pathways in hAT ex vivo and hPAs and hPBMCs in vitro; all phosphorylation events were saturable at leptin and amylin concentrations of ∼50 and ∼20 ng/ml, respectively. The effects of leptin and amylin on STAT3 phosphorylation in hPAs and hPBMCs in vitro were totally abolished under endoplasmic reticulum stress and/or in the presence of a STAT3 inhibitor. Results similar to those in the in vitro studies were observed in hAT studied ex vivo. CONCLUSIONS - Leptin and amylin activate overlapping intracellular signaling pathways in humans and have additive, but not synergistic, effects in signaling pathways studied in hPTs in vitro and ex vivo.

Original languageEnglish (US)
Pages (from-to)132-138
Number of pages7
JournalDiabetes Care
Volume34
Issue number1
DOIs
StatePublished - Jan 1 2011

Fingerprint

Islet Amyloid Polypeptide
Leptin
STAT3 Transcription Factor
Adipose Tissue
Adipocytes
Blood Cells
In Vitro Techniques
Phosphorylation
Leptin Receptors
AMP-Activated Protein Kinases
Endoplasmic Reticulum Stress
Extracellular Signal-Regulated MAP Kinases

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Cite this

Leptin and amylin act in an additive manner to activate overlapping signaling pathways in peripheral tissues : In vitro and ex vivo studies in humans. / Moon, Hyun Seuk; Chamberland, John P.; Diakopoulos, Kalliope N.; Fiorenza, Christina G.; Ziemke, Florencia; Schneider, Benjamin; Mantzoros, Christos S.

In: Diabetes Care, Vol. 34, No. 1, 01.01.2011, p. 132-138.

Research output: Contribution to journalArticle

Moon, Hyun Seuk ; Chamberland, John P. ; Diakopoulos, Kalliope N. ; Fiorenza, Christina G. ; Ziemke, Florencia ; Schneider, Benjamin ; Mantzoros, Christos S. / Leptin and amylin act in an additive manner to activate overlapping signaling pathways in peripheral tissues : In vitro and ex vivo studies in humans. In: Diabetes Care. 2011 ; Vol. 34, No. 1. pp. 132-138.
@article{2df233b275904ef3a9885254a97e2779,
title = "Leptin and amylin act in an additive manner to activate overlapping signaling pathways in peripheral tissues: In vitro and ex vivo studies in humans",
abstract = "OBJECTIVE - Amylin interacts with leptin to alter metabolism. We evaluated, for the first time, amylin- and/or leptin-activated signaling pathways in human peripheral tissues (hPTs). RESEARCH DESIGN AND METHODS - Leptin and amylin signaling studies were performed in vitro in human primary adipocytes (hPAs) and human peripheral blood mononuclear cells (hPBMCs) and ex vivo in human adipose tissue (hAT) from male versus female subjects, obese versus lean subjects, and subjects with subcutaneous versus omental adipose tissue. RESULTS - The long form of leptin receptor was expressed in human tissues and cells studied in ex vivo and in vitro, respectively. Leptin and amylin alone and in combination activate signal transducer and activator of transcription 3 (STAT3), AMP-activated protein kinase, Akt, and extracellular signal-regulated kinase signaling pathways in hAT ex vivo and hPAs and hPBMCs in vitro; all phosphorylation events were saturable at leptin and amylin concentrations of ∼50 and ∼20 ng/ml, respectively. The effects of leptin and amylin on STAT3 phosphorylation in hPAs and hPBMCs in vitro were totally abolished under endoplasmic reticulum stress and/or in the presence of a STAT3 inhibitor. Results similar to those in the in vitro studies were observed in hAT studied ex vivo. CONCLUSIONS - Leptin and amylin activate overlapping intracellular signaling pathways in humans and have additive, but not synergistic, effects in signaling pathways studied in hPTs in vitro and ex vivo.",
author = "Moon, {Hyun Seuk} and Chamberland, {John P.} and Diakopoulos, {Kalliope N.} and Fiorenza, {Christina G.} and Florencia Ziemke and Benjamin Schneider and Mantzoros, {Christos S.}",
year = "2011",
month = "1",
day = "1",
doi = "10.2337/dc10-0518",
language = "English (US)",
volume = "34",
pages = "132--138",
journal = "Diabetes Care",
issn = "1935-5548",
publisher = "American Diabetes Association Inc.",
number = "1",

}

TY - JOUR

T1 - Leptin and amylin act in an additive manner to activate overlapping signaling pathways in peripheral tissues

T2 - In vitro and ex vivo studies in humans

AU - Moon, Hyun Seuk

AU - Chamberland, John P.

AU - Diakopoulos, Kalliope N.

AU - Fiorenza, Christina G.

AU - Ziemke, Florencia

AU - Schneider, Benjamin

AU - Mantzoros, Christos S.

PY - 2011/1/1

Y1 - 2011/1/1

N2 - OBJECTIVE - Amylin interacts with leptin to alter metabolism. We evaluated, for the first time, amylin- and/or leptin-activated signaling pathways in human peripheral tissues (hPTs). RESEARCH DESIGN AND METHODS - Leptin and amylin signaling studies were performed in vitro in human primary adipocytes (hPAs) and human peripheral blood mononuclear cells (hPBMCs) and ex vivo in human adipose tissue (hAT) from male versus female subjects, obese versus lean subjects, and subjects with subcutaneous versus omental adipose tissue. RESULTS - The long form of leptin receptor was expressed in human tissues and cells studied in ex vivo and in vitro, respectively. Leptin and amylin alone and in combination activate signal transducer and activator of transcription 3 (STAT3), AMP-activated protein kinase, Akt, and extracellular signal-regulated kinase signaling pathways in hAT ex vivo and hPAs and hPBMCs in vitro; all phosphorylation events were saturable at leptin and amylin concentrations of ∼50 and ∼20 ng/ml, respectively. The effects of leptin and amylin on STAT3 phosphorylation in hPAs and hPBMCs in vitro were totally abolished under endoplasmic reticulum stress and/or in the presence of a STAT3 inhibitor. Results similar to those in the in vitro studies were observed in hAT studied ex vivo. CONCLUSIONS - Leptin and amylin activate overlapping intracellular signaling pathways in humans and have additive, but not synergistic, effects in signaling pathways studied in hPTs in vitro and ex vivo.

AB - OBJECTIVE - Amylin interacts with leptin to alter metabolism. We evaluated, for the first time, amylin- and/or leptin-activated signaling pathways in human peripheral tissues (hPTs). RESEARCH DESIGN AND METHODS - Leptin and amylin signaling studies were performed in vitro in human primary adipocytes (hPAs) and human peripheral blood mononuclear cells (hPBMCs) and ex vivo in human adipose tissue (hAT) from male versus female subjects, obese versus lean subjects, and subjects with subcutaneous versus omental adipose tissue. RESULTS - The long form of leptin receptor was expressed in human tissues and cells studied in ex vivo and in vitro, respectively. Leptin and amylin alone and in combination activate signal transducer and activator of transcription 3 (STAT3), AMP-activated protein kinase, Akt, and extracellular signal-regulated kinase signaling pathways in hAT ex vivo and hPAs and hPBMCs in vitro; all phosphorylation events were saturable at leptin and amylin concentrations of ∼50 and ∼20 ng/ml, respectively. The effects of leptin and amylin on STAT3 phosphorylation in hPAs and hPBMCs in vitro were totally abolished under endoplasmic reticulum stress and/or in the presence of a STAT3 inhibitor. Results similar to those in the in vitro studies were observed in hAT studied ex vivo. CONCLUSIONS - Leptin and amylin activate overlapping intracellular signaling pathways in humans and have additive, but not synergistic, effects in signaling pathways studied in hPTs in vitro and ex vivo.

UR - http://www.scopus.com/inward/record.url?scp=79951716553&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79951716553&partnerID=8YFLogxK

U2 - 10.2337/dc10-0518

DO - 10.2337/dc10-0518

M3 - Article

VL - 34

SP - 132

EP - 138

JO - Diabetes Care

JF - Diabetes Care

SN - 1935-5548

IS - 1

ER -