Abstract
GPR120 is implicated as a lipid receptor in the oro-sensory detection of dietary fatty acids. However, the effects of GPR120 activation on dietary fat intake or obesity are not clearly understood. We investigated to determine whether the binding of TUG891, a novel GPR120 agonist, to lingual GPR120 modulates fat preference in mice. We explored the effects of TUG891 on obesity-related hormones and conducted behavioral choice tests on mice to better understand the physiologic relevance of the action of TUG891. In cultured mouse and human taste bud cells (TBCs), TUG891 induced a rapid increase in Ca2+ by acting on GPR120. A long-chain dietary fatty acid, linoleic acid (LA), also recruited Ca2+ via GPR120 in human and mouse TBCs. Both TUG891 and LA induced ERK1/2 phosphorylation and enhanced in vitro release of glucagon-like peptide-1 from cultured human and mouse TBCs. In situ application of TUG891 onto the tongue of anesthetized mice triggered the secretion of pancreatobiliary juice, probably via the tongue-brain-gut axis. Furthermore, lingual application of TUG891 altered circulating concentrations of cholecystokinin and adipokines, associated with decreased circulating LDL, in conscious mice. In behavioral tests, mice exhibited a spontaneous preference for solutions containing either TUG891 or LA instead of a control. However, addition of TUG891 to a solution containing LA significantly curtailed fatty acid preference. Our study demonstrates that TUG891 binds to lingual GPR120 receptors, activates the tongue-brain-gut axis, and modulates fat preference. These findings may support the development of new fat taste analogs that can change the approach to obesity prevention and treatment.
Highlights
GPR120 is implicated as a lipid receptor in the oro-sensory detection of dietary fatty acids
TUG891-induced increases in [intracellular free calcium concentrations (Ca2+]i) were completely abolished in taste bud cell (TBC) that were preincubated with AH7614, a selective blocker of GPR120 (Fig. 1C, D)
Schilperoort et al [20] have reported that this agonist was able to decrease fat mass, body weight, food intake, and increase fat oxidation and mitochondrial respiration in brown adipose tissue in mice. Because this agent appears to act on multiple targets, we were intrigued to find out whether the antiobesity effects of TUG891 involved the modulation of fat taste preference via its action on lingual GPR120, and whether TUG891 could trigger gut activation through tongue-brain-axis
Summary
GPR120 is implicated as a lipid receptor in the oro-sensory detection of dietary fatty acids. We investigated to determine whether the binding of TUG891, a novel GPR120 agonist, to lingual GPR120 modulates fat preference in mice. Our study demonstrates that TUG891 binds to lingual GPR120 receptors, activates the tongue-brain-gut axis, and modulates fat preference. These findings may support the development of new fat taste analogs that can change the approach to obesity prevention and treatment.—Murtaza, B., A. Novel GPR120 agonist TUG891 modulates fat taste perception and preference and activates tongue-brain-gut axis in mice. It becomes obvious to think of developing and testing lipid taste modifiers that can bind to fat taste receptors like CD36 and GPR120 on taste buds and bring fewer calories, as a novel way of modulating obesity and related disorders
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