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

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Citation

Moon HS, Huh JY, Dincer F, Schneider BE, Hasselgren PO, Mantzoros CS

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

Diabetes. 2015 Mar;64(3):828-39. doi: 10.2337/db14-0625. Epub 2014 Sep 23.

PubMed ID
25249580 [ View in PubMed
]
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-kappaB, and/or IKKalpha/beta without any differences between male versus female and obese versus lean subjects. All signaling pathways were saturable at approximately 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.

DrugBank Data that Cites this Article

Drugs
Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
MetreleptinLeptin receptorProteinHumans
Yes
Agonist
Details