Identification and saturable nature of signaling pathways induced by metreleptin in humans: Comparative evaluation of in vivo, ex vivo, and in vitro administration

Hyun Seuk Moon, Joo Young Huh, Fadime Dincer, Benjamin E. Schneider, Per Olof Hasselgren, Christos S. Mantzoros

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Signaling pathways activated by leptin in metabolically important organs have largely been studied only in animal and/or cell culture studies. In this study, we examined whether leptin has similar effects in human peripheral tissues in vivo, ex vivo, and in vitro and whether the response would be different in lean and obese humans. For in vivo leptin signaling, metreleptin was administered and muscle, adipose tissue, and peripheral blood mononuclear cells were taken for analysis of signal activation. Experiments were also done ex vivo and with primary cultured cells in vitro. The signal activation was compared between male versus female and obese versus lean humans. Acute in vivo, ex vivo, and/or in vitro metreleptin administration similarly activated STAT3, AMPK, ERK1/2, Akt, mTOR, NF-κB, and/or IKKα/β without any differences between male versus female and obese versus lean subjects. All signaling pathways were saturable at ∼30-50 ng/mL, consistent with the clinical evidence showing no additional effect(s) in obese subjects who already have high levels of leptin. Our data provide novel information on downstream effectors of metreleptin action in humans that may have therapeutic implications.

Original languageEnglish (US)
Pages (from-to)828-839
Number of pages12
JournalDiabetes
Volume64
Issue number3
DOIs
StatePublished - Mar 1 2015

Fingerprint

Leptin
Activation Analysis
AMP-Activated Protein Kinases
Adipose Tissue
Cultured Cells
Blood Cells
Cell Culture Techniques
Muscles
metreleptin
In Vitro Techniques
Therapeutics

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Identification and saturable nature of signaling pathways induced by metreleptin in humans : Comparative evaluation of in vivo, ex vivo, and in vitro administration. / Moon, Hyun Seuk; Huh, Joo Young; Dincer, Fadime; Schneider, Benjamin E.; Hasselgren, Per Olof; Mantzoros, Christos S.

In: Diabetes, Vol. 64, No. 3, 01.03.2015, p. 828-839.

Research output: Contribution to journalArticle

Moon, Hyun Seuk ; Huh, Joo Young ; Dincer, Fadime ; Schneider, Benjamin E. ; Hasselgren, Per Olof ; Mantzoros, Christos S. / Identification and saturable nature of signaling pathways induced by metreleptin in humans : Comparative evaluation of in vivo, ex vivo, and in vitro administration. In: Diabetes. 2015 ; Vol. 64, No. 3. pp. 828-839.
@article{c52c7d9454394e0f85734bd0183a0391,
title = "Identification and saturable nature of signaling pathways induced by metreleptin in humans: Comparative evaluation of in vivo, ex vivo, and in vitro administration",
abstract = "Signaling pathways activated by leptin in metabolically important organs have largely been studied only in animal and/or cell culture studies. In this study, we examined whether leptin has similar effects in human peripheral tissues in vivo, ex vivo, and in vitro and whether the response would be different in lean and obese humans. For in vivo leptin signaling, metreleptin was administered and muscle, adipose tissue, and peripheral blood mononuclear cells were taken for analysis of signal activation. Experiments were also done ex vivo and with primary cultured cells in vitro. The signal activation was compared between male versus female and obese versus lean humans. Acute in vivo, ex vivo, and/or in vitro metreleptin administration similarly activated STAT3, AMPK, ERK1/2, Akt, mTOR, NF-κB, and/or IKKα/β without any differences between male versus female and obese versus lean subjects. All signaling pathways were saturable at ∼30-50 ng/mL, consistent with the clinical evidence showing no additional effect(s) in obese subjects who already have high levels of leptin. Our data provide novel information on downstream effectors of metreleptin action in humans that may have therapeutic implications.",
author = "Moon, {Hyun Seuk} and Huh, {Joo Young} and Fadime Dincer and Schneider, {Benjamin E.} and Hasselgren, {Per Olof} and Mantzoros, {Christos S.}",
year = "2015",
month = "3",
day = "1",
doi = "10.2337/db14-0625",
language = "English (US)",
volume = "64",
pages = "828--839",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "3",

}

TY - JOUR

T1 - Identification and saturable nature of signaling pathways induced by metreleptin in humans

T2 - Comparative evaluation of in vivo, ex vivo, and in vitro administration

AU - Moon, Hyun Seuk

AU - Huh, Joo Young

AU - Dincer, Fadime

AU - Schneider, Benjamin E.

AU - Hasselgren, Per Olof

AU - Mantzoros, Christos S.

PY - 2015/3/1

Y1 - 2015/3/1

N2 - Signaling pathways activated by leptin in metabolically important organs have largely been studied only in animal and/or cell culture studies. In this study, we examined whether leptin has similar effects in human peripheral tissues in vivo, ex vivo, and in vitro and whether the response would be different in lean and obese humans. For in vivo leptin signaling, metreleptin was administered and muscle, adipose tissue, and peripheral blood mononuclear cells were taken for analysis of signal activation. Experiments were also done ex vivo and with primary cultured cells in vitro. The signal activation was compared between male versus female and obese versus lean humans. Acute in vivo, ex vivo, and/or in vitro metreleptin administration similarly activated STAT3, AMPK, ERK1/2, Akt, mTOR, NF-κB, and/or IKKα/β without any differences between male versus female and obese versus lean subjects. All signaling pathways were saturable at ∼30-50 ng/mL, consistent with the clinical evidence showing no additional effect(s) in obese subjects who already have high levels of leptin. Our data provide novel information on downstream effectors of metreleptin action in humans that may have therapeutic implications.

AB - Signaling pathways activated by leptin in metabolically important organs have largely been studied only in animal and/or cell culture studies. In this study, we examined whether leptin has similar effects in human peripheral tissues in vivo, ex vivo, and in vitro and whether the response would be different in lean and obese humans. For in vivo leptin signaling, metreleptin was administered and muscle, adipose tissue, and peripheral blood mononuclear cells were taken for analysis of signal activation. Experiments were also done ex vivo and with primary cultured cells in vitro. The signal activation was compared between male versus female and obese versus lean humans. Acute in vivo, ex vivo, and/or in vitro metreleptin administration similarly activated STAT3, AMPK, ERK1/2, Akt, mTOR, NF-κB, and/or IKKα/β without any differences between male versus female and obese versus lean subjects. All signaling pathways were saturable at ∼30-50 ng/mL, consistent with the clinical evidence showing no additional effect(s) in obese subjects who already have high levels of leptin. Our data provide novel information on downstream effectors of metreleptin action in humans that may have therapeutic implications.

UR - http://www.scopus.com/inward/record.url?scp=84962110354&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962110354&partnerID=8YFLogxK

U2 - 10.2337/db14-0625

DO - 10.2337/db14-0625

M3 - Article

C2 - 25249580

AN - SCOPUS:84962110354

VL - 64

SP - 828

EP - 839

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 3

ER -