Sweet taste receptor deficient mice have decreased adiposity and increased bone mass.
Functional expression of sweet taste receptors (T1R2 and T1R3) has been reported in numerous metabolic tissues, including the gut, pancreas, and, more recently, in adipose tissue. It has been suggested that sweet taste receptors in these non-gustatory tissues may play a role in systemic energy balance and metabolism. Smaller adipose depots have been reported in T1R3 knockout mice on a high carbohydrate diet, and sweet taste receptors have been reported to regulate adipogenesis in vitro. To assess the potential contribution of sweet taste receptors to adipose tissue biology, we investigated the adipose tissue phenotypes of T1R2 and T1R3 knockout mice. Here we provide data to demonstrate that when fed an obesogenic diet, both T1R2 and T1R3 knockout mice have reduced adiposity and smaller adipocytes. Although a mild glucose intolerance was observed with T1R3 deficiency, other metabolic variables analyzed were similar between genotypes. In addition, food intake, respiratory quotient, oxygen consumption, and physical activity were unchanged in T1R2 knockout mice. Although T1R2 deficiency did not affect adipocyte number in peripheral adipose depots, the number of bone marrow adipocytes is significantly reduced in these knockout animals. Finally, we present data demonstrating that T1R2 and T1R3 knockout mice have increased cortical bone mass and trabecular remodeling. This report identifies novel functions for sweet taste receptors in the regulation of adipose and bone biology, and suggests that in these contexts, T1R2 and T1R3 are either dependent on each other for activity or have common independent effects in vivo.
Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, Michigan, United States of America.
Becky R
BR
Simon
Molecular & Integrative Physiology, University of Michigan, Ann Arbor, Michigan, United States of America.
Brian S
BS
Learman
Molecular & Integrative Physiology, University of Michigan, Ann Arbor, Michigan, United States of America.
Sebastian D
SD
Parlee
Molecular & Integrative Physiology, University of Michigan, Ann Arbor, Michigan, United States of America.
Erica L
EL
Scheller
Molecular & Integrative Physiology, University of Michigan, Ann Arbor, Michigan, United States of America.
Hiroyuki
H
Mori
Molecular & Integrative Physiology, University of Michigan, Ann Arbor, Michigan, United States of America ; Musculoskeletal Research, Lilly Research Laboratories, Indianapolis, Indiana, United States of America.
William P
WP
Cawthorn
Molecular & Integrative Physiology, University of Michigan, Ann Arbor, Michigan, United States of America.
Xiaomin
X
Ning
Musculoskeletal Research, Lilly Research Laboratories, Indianapolis, Indiana, United States of America.
Venkatesh
V
Krishnan
Musculoskeletal Research, Lilly Research Laboratories, Indianapolis, Indiana, United States of America.
Yanfei L
YL
Ma
Cardiovascular and Metabolic Disease, MedImmune LLC, Gaithersburg, Maryland, United States of America ; Diabetes and Obesity Research Center, Sanford-Burnham Medical Research Institute, Orlando, Florida, United States of America.
Björn
B
Tyrberg
Program in Cellular and Molecular Biology, University of Michigan, Ann Arbor, Michigan, United States of America ; Molecular & Integrative Physiology, University of Michigan, Ann Arbor, Michigan, United States of America ; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, United States of America.
Ormond A
OA
MacDougald
D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism; D050154:Adiposity / Q000235:genetics*; D000818:Animals; D015519:Bone Density; D016723:Bone Remodeling / Q000235:genetics; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism*; D048429:Cell Size; D004032:Diet; D005947:Glucose / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency*; D013650:Taste Buds / Q000378:metabolism*
D043562:Receptors, G-Protein-Coupled; C431926:taste receptors, type 1; D005947:Glucose