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Journal Articles Obesity Year : 2014

Acute oral metformin enhances satiation and activates brainstem nesfatinergic neurons

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Abstract

Objective: The study was designed to determine metformin effects on meal pattern, gastric emptying, energy expenditure, and to identify metformin-sensitive neurons and their phenotype. Methods: This study was performed on C57BL/6J and obese/diabetic (db/db) mice. Metformin (300 mg/kg) was administered by oral gavage. Food intake, meal pattern, oxygen consumption (VO2), and carbon dioxide production (VCO2) were obtained using an Oxylet Physiocage System. Gastric emptying assay and real-time RT-PCR from dorsal vagal complex extracts were also performed. C-Fos expression was used as a marker of neuronal activation. Phenotypic characterization of activated neurons was performed using either proopiomelanocortin (POMC)-Tau-Topaz GFP transgenic mice or NUCB2/nesfatin-1 and tyrosine hydroxylase (TH) labeling. Results: Acute per os metformin treatment slowed down gastric emptying, reduced meal size, but not meal number in a leptin-independent manner, and transiently decreased energy expenditure in a leptin-dependent manner. Metformin specifically activated central circuitry within the brainstem, independently of vagal afferents. Finally, while POMC neurons seemed sparsely activated, we report that a high proportion of the c-Fos positive cells were nesfatinergic neurons, some of which coexpressing TH. Conclusions: Altogether, these results show that metformin modifies satiation by activating brainstem circuitry and suggest that NUCB2/nesfatin-1 could be involved in this metformin effect
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hal-02630580 , version 1 (27-05-2020)

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Thaïs Rouquet, Pierre Clément, Stéphanie Gaigé, Catherine Tardivel, Julien Roux, et al.. Acute oral metformin enhances satiation and activates brainstem nesfatinergic neurons. Obesity, 2014, 22 (12), pp.2552-2562. ⟨10.1002/oby.20902⟩. ⟨hal-02630580⟩
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