Leptin analog antagonizes leptin effects on food intake and body weight but mimics leptin-induced vagal afferent activation.

Leptin analog antagonizes leptin effects on food intake and body weight but mimics leptin-induced vagal afferent activation. Research Abstract Details 

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Leptin analog antagonizes leptin effects on food intake and body weight but mimics leptin-induced vagal afferent activation. Abstract Text:

J H Peters,S M Simasko,R C Ritter,

A recombinantly produced murine leptin analog (MLA) antagonizes leptin-induced signaling in cell lines that express the long form of the leptin receptor. However, the effects of MLA on the activity of leptin-sensitive neurons and on central neural controls of food intake have not been reported. Here we report effects of MLA on food intake and body weight in adult rats and on the activity of cultured rat vagal afferent neurons. Daily intracerebroventricular coinjection of MLA with exogenous leptin significantly attenuated leptin-induced reduction of 48-h food intake and body weight. Coinjection of MLA with leptin also reduced leptin-induced phosphorylation of signal transducer and activator of transcription 3 (STAT3) in the hypothalamus. In addition, chronic intracerebroventricular MLA infusion over 14 d via osmotic minipumps significantly increased daily food intake, rate of body weight gain, fat-pad mass, and circulating plasma leptin concentrations. Surprisingly, however, MLA did not antagonize leptin-evoked increases in cytosolic calcium concentrations in vagal afferent neurons in primary culture. Rather, MLA itself produced acute activation selectively in leptin-responsive vagal afferent neurons. These data suggest that MLA is an antagonist for the central effects of leptin on food intake and body weight but an agonist at sites where leptin induces acute neuronal activation. This mixed antagonist/agonist action suggests either 1) that the coupling of a single leptin receptor (ObRb) to acute activation of neurons occurs by a signaling mechanism different from those that mediate centrally evoked reductions in food intake and body weight or 2) that acute neuronal activation and centrally induced reductions of food intake and body weight are mediated by different leptin receptor subtypes.

Leptin analog antagonizes leptin effects on food intake and body weight but mimics leptin-induced vagal afferent activation. Publishing Authors By Initials

JH Peters,SM Simasko,RC Ritter,

For similar nervous system: peripheral nervous system: autonomic nervous system: autonomic pathways: vagus nerve research abstracts see: nervous system: peripheral nervous system: autonomic nervous system: autonomic pathways: vagus nerve research

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Leptin analog antagonizes leptin effects on food intake and body weight but mimics leptin-induced vagal afferent activation. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Endocrinology

VOLUME: 148

Page Numbers: 2878-85

Journal Abbreviation: Endocrinology

ISSN: 0013-7227

DAY: 15

MONTH: 03

YEAR: 2007

Leptin analog antagonizes leptin effects on food intake and body weight but mimics leptin-induced vagal afferent activation. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 375040

Leptin analog antagonizes leptin effects on food intake and body weight but mimics leptin-induced vagal afferent activation. Keywords Mesh Terms:

KEYWORDS: Vagus Nerve

MESH TERMS: metabolism

Chemical & Substance for Abstract: Leptin analog antagonizes leptin effects on food intake and body weight but mimics leptin-induced vagal afferent activation. Information

Substance Name: murine leptin analog

Registry Number: 0

Grant and Affiliation Information for Leptin analog antagonizes leptin effects on food intake and body weight but mimics leptin-induced vagal afferent activation.

AFFILIATION: Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, OR 97239, USA. petersj.OHSU@gmail.com

Country: United States

AGENCY: United States NINDS

GRANT: NS 20561

ACRONYM: NS

MEDLINETA: Endocrinology

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