Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/128569
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Type: Journal article
Title: Leptin signaling in vagal afferent neurons supports the absorption and storage of nutrients from high-fat diet
Author: Huang, K.P.
Goodson, M.L.
Vang, W.
Li, H.
Page, A.J.
Raybould, H.E.
Citation: International Journal of Obesity, 2021; 45(2):348-357
Publisher: Springer Nature
Issue Date: 2021
ISSN: 0307-0565
1476-5497
Statement of
Responsibility: 
Kuei-Pin Huang, Michael L. Goodson, Wendie Vang, Hui Li, Amanda J. Page, Helen E. Raybould
Abstract: Objective: Activation of vagal afferent neurons (VAN) by postprandial gastrointestinal signals terminates feeding and facilitates nutrient digestion and absorption. Leptin modulates responsiveness of VAN to meal-related gastrointestinal signals. Rodents with high-fat diet (HF) feeding develop leptin resistance that impairs responsiveness of VAN. We hypothesized that lack of leptin signaling in VAN reduces responses to meal-related signals, which in turn decreases absorption of nutrients and energy storage from high-fat, calorically dense food. Methods: Mice with conditional deletion of the leptin receptor from VAN (Nav1.8-Cre/LepRfl/fl; KO) were used in this study. Six-week-old male mice were fed a 45% HF for 4 weeks; metabolic phenotype, food intake, and energy expenditure were measured. Absorption and storage of nutrients were investigated in the refed state. Results: After 4 weeks of HF feeding, KO mice gained less body weight and fat mass that WT controls, but this was not due to differences in food intake or energy expenditure. KO mice had reduced expression of carbohydrate transporters and absorption of carbohydrate in the jejunum. KO mice had fewer hepatic lipid droplets and decreased expression of de novo lipogenesis-associated enzymes and lipoproteins for endogenous lipoprotein pathway in liver, suggesting decreased long-term storage of carbohydrate in KO mice. Conclusions: Impairment of leptin signaling in VAN reduces responsiveness to gastrointestinal signals, which reduces intestinal absorption of carbohydrates and de novo lipogenesis resulting in reduced long-term energy storage. This study reveals a novel role of vagal afferents to support digestion and energy storage that may contribute to the effectiveness of vagal blockade to induce weight loss.
Description: Published online: 11 September 2020
Rights: © The Author(s), under exclusive licence to Springer Nature Limited 2020
DOI: 10.1038/s41366-020-00678-1
Grant ID: http://purl.org/au-research/grants/arc/DP140102203
DK076169
DK115255
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