Abstracts - Association for Chemoreception Sciences

#P167 POSTER SESSION IV:
CHEMICAL SIGNALING AND BEHAVIOR;
ANIMAL BEHAVIOR/PSYCHOPHYSICS;
CHEMOSENSATION AND METABOLISM;
VOMERONSASAL AND CHEMICAL
COMMUNICATION
#P168 POSTER SESSION IV:
CHEMICAL SIGNALING AND BEHAVIOR;
ANIMAL BEHAVIOR/PSYCHOPHYSICS;
CHEMOSENSATION AND METABOLISM;
VOMERONSASAL AND CHEMICAL
COMMUNICATION
A role for bitter taste receptors in thyroid toxicity and
hormone production
Adam A. Clark 1,2 , Cedrick D. Dotson 1 , Amanda E.T. Elson 1 ,
Nanette I. Steinle 3 , Steven D. Munger 1,2,3
1
University of Maryland Baltimore Department of Anatomy and
Neurobiology Baltimore, MD, USA, 2 University of Maryland Baltimore
Program in Toxicology Baltimore, MD, USA, 3 University of Maryland
Baltimore Department of Medicine Baltimore, MD, USA
Bitterness is associated with toxicity. Bitter compounds activate
a small family of G protein-coupled taste receptors (T2Rs)
expressed in the taste buds. T2Rs are also found in non-gustatory
tissues (e.g., the respiratory and gastrointestinal systems),
suggesting that many ingested or inhaled toxins could have
broad physiologic effects. We report that T2Rs are expressed
in thyroid follicular cells (FCs), where they modulate iodide
efflux. Immunohistochemical and PCR analyses show that
numerous T2Rs as well as the T2R-associated G protein subunit
a-gustducin are expressed in human and rodent FCs and in a
human follicular cell line, Nthy-Ori 3-1. Thyroid stimulating
hormone (TSH)-dependent Ca 2+ signals, an important regulator
of iodide efflux from FCs, were significantly reduced in Nthy-
Ori 3-1 cells by the T2R ligands denatonium benzoate (DB),
chloramphenicol (Chlor) and cycloheximide (Cyx). By contrast,
the T2R38 ligand 6-n-propylthiouracil (PROP) had no effect
on TSH-dependent Ca 2+ signals, likely because this cell line
expresses only the “non-taster” T2R38 variant. DB, Chlor and
Cyx also significantly reduced TSH-dependent iodide efflux from
Nthy-Ori 3-1 cells. Decreased iodide efflux in vivo should result in
decreased production of the thyroid hormones triiodothyronine
(T3) and thyroxine (T4). Consistent with this, we found that
a nonsynonymous polymorphism in T2R42 is associated
with lower free T3 and T4 levels in a human cohort. Thyroid
hormones can affect energy expenditure, thermoregulation, body
weight, and body composition. T2Rs may be a useful target for
pharmacologic regulation of these endocrine signals, perhaps
leading to new interventions for chronic morbidities involving
fatigue or obesity. Acknowledgements: Support: NIDCD (R01
DC010110), NIDDK (P30 DK072488).
Metabolic effects of long-term sweetener consumption
Maartje CP Geraedts 1 , Tatsuyuki Takahashi 1 , Stephan Vigues 1 ,
Cedric Uytingco 1 , Steven D Munger 1,2
1
University of Maryland School of Medicine, Department of Anatomy
& Neurobiology Baltimore, MD, USA, 2 University of Maryland School
of Medicine, Department of Medicine, Division of Endocrinology,
Diabetes and Nutrition Baltimore, MD, USA
The sweet taste receptor T1R2+T1R3 responds to diverse
gustatory stimuli including sugars and low calorie sweeteners
(LCS). In intestinal enteroendocrine L cells, T1R2+T1R3
couples glucose stimulation to the secretion of insulinotropic
hormone glucagon-like peptide-1 (GLP-1). While the
preponderance of in vivo evidence indicates that LCS do not
impact glucose homeostasis, the responsiveness of T1R2+T1R3
to natural and artificial LCS suggests that these compounds
could exert extraoral effects. To address this issue, we have
initiated long-term sweetener (300 mM sucrose, Su; 1 mM
sucralose, Sa; 10 mM cyclamate, Cy; 3 mM acesulfame K; 5 mM
rebaudioside A) consumption studies in mice with (T1R3 +/+ ) or
without (T1R3 -/- ) a functional sweet taste receptor. Mice (4 w.o.)
are maintained for 3, 6, 9 or 12 mo. on normal chow diets along
with ad lib water containing one of the sweeteners. Cy serves as
a negative control as it is not an agonist for mouse T1R2+T1R3.
Mice are assessed for food and fluid intake, sweet taste
preference, body weight, body fat, metrics of glucose and insulin
homeostasis, and glucose-stimulated GLP-1 secretion from ileum
and colon explants. Initial results indicate that both T1R3 +/+
and -/- mice maintained on 300mM Su have significantly higher
body fat content than either Sa- or Cy-treated mice. By contrast,
Sa-treated mice show a strong potentiation of glucose-stimulated
GLP-1 secretion (as compared to Su- or Cy-treated mice) at 3
mo, with reduced potentiation at later time points. Interestingly,
glucose tolerance tests revealed no significant differences
in glucose or insulin levels across these sweetener groups.
Ongoing assessments of all five sweeteners will be presented.
Acknowledgements: Tate&Lyle and NIDCD (DC010110)
POSTER PRESENTATIONS
Abstracts are printed as submitted by the author(s).
92