The Gustatory Signaling Pathway and Bitter Taste Receptors Affect the Development of Obesity and Adipocyte Metabolism in Mice.

Bert Avau,Jorien Laermans,H Roger Lijnen,Inge Depoortere,Sandra Steensels,Johan Buyse,Jan Tack,Jens Lesuisse,Laurien Vancleef,Dries Bauters,John I Glendinning

doi:10.1371/journal.pone.0145538

Bert Avau, Jorien Laermans + Show 9 more

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https://doi.org/10.1371/journal.pone.0145538

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Journal: PLOS ONE	Publication Date: Dec 21, 2015
Citations: 58	License type: CC BY 4.0

Affiliation: KU Leuven

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Intestinal chemosensory signaling pathways involving the gustatory G-protein, gustducin, and bitter taste receptors (TAS2R) have been implicated in gut hormone release. Alterations in gut hormone profiles may contribute to the success of bariatric surgery. This study investigated the involvement of the gustatory signaling pathway in the development of diet-induced obesity and the therapeutic potential of targeting TAS2Rs to induce body weight loss. α-gustducin-deficient (α-gust-/-) mice became less obese than wild type (WT) mice when fed a high-fat diet (HFD). White adipose tissue (WAT) mass was lower in α-gust-/- mice due to increased heat production as a result of increases in brown adipose tissue (BAT) thermogenic activity, involving increased protein expression of uncoupling protein 1. Intra-gastric treatment of obese WT and α-gust-/- mice with the bitter agonists denatonium benzoate (DB) or quinine (Q) during 4 weeks resulted in an α-gustducin-dependent decrease in body weight gain associated with a decrease in food intake (DB), but not involving major changes in gut peptide release. Both WAT and 3T3-F442A pre-adipocytes express TAS2Rs. Treatment of pre-adipocytes with DB or Q decreased differentiation into mature adipocytes. In conclusion, interfering with the gustatory signaling pathway protects against the development of HFD-induced obesity presumably through promoting BAT activity. Intra-gastric bitter treatment inhibits weight gain, possibly by directly affecting adipocyte metabolism.

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Obesity is one of the major healthcare problems, affecting millions of people worldwide [1]
This study investigated the involvement of the gustatory signaling pathway in the development of diet-induced obesity and the therapeutic potential of targeting TAS2Rs to induce body weight loss. α-gustducin-deficient (α-gust-/-) mice became less obese than wild type (WT) mice when fed a highfat diet (HFD)
In view of the inhibitory effect after intra-gastric administration of bitter on food intake in mice [14] and on appetite signaling in humans [19], we investigated whether prolonged intra-gastric administration of bitter agonists influences food intake and body weight in high-fat diet induced obese wild type (WT) mice, but not in obese α-gust-/- mice

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Introduction

Obesity is one of the major healthcare problems, affecting millions of people worldwide [1]. The expression of stomach taste signaling elements has been reported to be altered in obese patients, with a decreased expression of the sweet/umami taste receptor TAS1R3, but an increased expression of the fatty acid receptor FFAR4 (GPR120), α-gustducin, PLCβ2 and TRPM5 [18]. These findings suggest that nutrient sensing via the taste signaling pathway may be altered during nutrient excess. In view of the inhibitory effect after intra-gastric administration of bitter on food intake in mice [14] and on appetite signaling in humans [19], we investigated whether prolonged intra-gastric administration of bitter agonists influences food intake and body weight in high-fat diet induced obese wild type (WT) mice, but not in obese α-gust-/- mice

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