title: Disruption of the sugar-sensing receptor T1R2 attenuates metabolic derangements associated with diet-induced obesity.
abstract: Sweet taste receptors (STRs) on the tongue mediate gustatory sweet sensing, but their expression in the gut, pancreas, and adipose tissue suggests a physiological contribution to whole body nutrient sensing and metabolism. However, little is known about the function and contribution of these sugar sensors during metabolic stress induced by overnutrition and subsequent obesity. Here, we investigated the effects of high-fat/low-carbohydrate (HF/LC) diet on glucose homeostasis and energy balance in mice with global disruption of the sweet taste receptor protein T1R2. We assessed body composition, energy balance, glucose homeostasis, and tissue-specific nutrient metabolism in T1R2 knockout (T1R2-KO) mice fed a HF/LC diet for 12 wk. HF/LC diet-fed T1R2-KO mice gained a similar amount of body mass as did WT mice, but had reduced fat mass and increased lean mass relative to WT mice. T1R2-KO mice were also hyperphagic and hyperactive. Ablation of the T1R2 sugar sensor protected mice from HF/LC diet-induced hyperinsulinemia and altered substrate utilization, including increased rates of glucose oxidation and decreased liver triglyceride (TG) accumulation, despite normal intestinal fat absorption. Finally, STRs (T1r2/T1r3) were upregulated in the adipose tissue of WT mice in response to HF/LC diet, and their expression positively correlated with fat mass and glucose intolerance. The chemosensory receptor T1R2, plays an important role in glucose homeostasis during diet-induced obesity through the regulation of yet to be identified molecular mechanisms that alter energy disposal and utilization in peripheral tissues.
authors.affiliation: Center for Metabolic Origins of Disease, Sanford Burnham Prebys Medical Discovery Institute, Orlando, Florida; and.
authors.forename: Kathleen R
authors.initials: KR
authors.lastname: Smith
authors.affiliation: Center for Metabolic Origins of Disease, Sanford Burnham Prebys Medical Discovery Institute, Orlando, Florida; and.
authors.forename: Tania
authors.initials: T
authors.lastname: Hussain
authors.affiliation: Center for Metabolic Origins of Disease, Sanford Burnham Prebys Medical Discovery Institute, Orlando, Florida; and.
authors.forename: Elnaz
authors.initials: E
authors.lastname: Karimian Azari
authors.affiliation: Center for Metabolic Origins of Disease, Sanford Burnham Prebys Medical Discovery Institute, Orlando, Florida; and.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Steiner
authors.affiliation: Center for Metabolic Origins of Disease, Sanford Burnham Prebys Medical Discovery Institute, Orlando, Florida; and.
authors.forename: Julio E
authors.initials: JE
authors.lastname: Ayala
authors.affiliation: Center for Metabolic Origins of Disease, Sanford Burnham Prebys Medical Discovery Institute, Orlando, Florida; and.|Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, Florida.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Pratley
authors.affiliation: Center for Metabolic Origins of Disease, Sanford Burnham Prebys Medical Discovery Institute, Orlando, Florida; and gkyriazis@sbpdiscovery.org.|Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, Florida.
authors.forename: George A
authors.identifier: http://orcid.org/0000-0001-9514-3482
authors.initials: GA
authors.lastname: Kyriazis
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000596:Amino Acids; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001823:Body Composition / Q000235:genetics*; D001835:Body Weight / Q000235:genetics; D002857:Chromium; D050528:Diet, Carbohydrate-Restricted; D059305:Diet, High-Fat; D004734:Energy Metabolism / Q000235:genetics*; D018149:Glucose Intolerance / Q000235:genetics* / Q000378:metabolism; D006706:Homeostasis; D006946:Hyperinsulinism / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009539:Nicotinic Acids; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000596:Amino Acids; D001786:Blood Glucose; D007328:Insulin; D009539:Nicotinic Acids; D043562:Receptors, G-Protein-Coupled; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; D014280:Triglycerides; C015240:glucose tolerance factor; C431926:taste receptors, type 1; D002857:Chromium
keywords: body composition; diabetes; hyperinsulinemia; obesity; sweet taste receptors