Castellina in Chianti 2013
Genes, Taste,
food choices
and health
R.Barale
Department of Biology
Genetics, Environmental Mutagenesis and
Epidemiology, Pisa University, Italy
Gli umani possono distinguere 5 classi
di sapori:
1)  dolce,
2)  acido,
3)  amaro,
4) salato e
5) umami, (glutammato).
taste perception
Taste:
sour and salty mediated by ion channels
Umami
umami, sweet, and bitter mediated by GPCR
TAS1R1 + 3
Panda lacks this gene
Figures by Chandrashekar et al., 2006
sweet
TAS1R2 + 3
bitter
25 TAS2Rs
The felids lack of this gene
Evoluzione opsine
Recettore
gustativi(40)
Bitter taste genes evolution: copy number of TAS2Rs
TAS2Rs genes are clustered in chromosome 7
and 12, close to the olfactive gene clusters
Olfactory receptors fam. 2
Cluster opsine
Olfactory receptors fam. 6
Cluster taste genes
Cluster taste genes
bitter taste perception and the genetic background
deorphanized hTAS2Rs/ligand pairs:
2-Acetylpyrazine*
Saccharin*
Caffeine ***
Absinthin#
Strychnine#
25 TAS2Rs
Humulone##
Phenylthiocarbamide
(PTC)**
Epicatechin*
Theobromine*
Amygdalin*
[*Li et al., patent application, US 2008/0038739; **Bufe et al., 2005; ***Behrens et al., 2004;# Brockhoff et al., 2007;
##Ley,
2008]
So far, cats are among mammals lacking the sweet gene; even close relatives
among the meat-eaters like hyenas and mongooses have it.
And cats lack other components of the ability to enjoy (and digest) sugars, such as glucokinase in
their livers—a key enzyme that controls the metabolism of carbohydrates and prevents glucose
from flooding the animal. Despite this, most major pet food manufacturers use corn or other grains
in their meals. This may be why cats are getting diabetes.
Dolphins and sea lions have lost func2onal copies of Tas1R3 (umami). Morehover dolphins have lost many bi?er taste genes (TAS2Rs) becoming close to fishes which posses only three bi?er taste genes. Bears family posses all
mammalian taste genes
and are omnivores
Panda lost umami taste by
mutation 4,2 millons years
ago which coincided with
dietary change to strictly
herbivorous life style
?
Arthur Fox
The story began in
1931 when ...
Fenylthiocarbammide
(PTC)
PTC can result extremely bitter or
tasteless
OR
And understand why some appreciate and other reject some foods
Ala-Val
Pro-Ala
Val-Ile
Distribuzione fenotipica della sensibilità al PTC
89%
100
PTC _SI
PTC _NO
80
60
40
20
11%
0
PTC_NO sono ~20% della Popolazione Eurepea
Summary of results of PTC tests in apes by Fisher et al.
(1939) mod da: Wooding S, Genetics, 172, 2015-23, 2006
Fisher
Chimpanzee
Gorilla
Orangutan
Gibbon
Total
Ford
Tested
27
2
3
4
36
Huxley
Taster
20
2
2
2
26
Non Taster
7
0
1
2
10 (28%)
*
Letter: Nature 440,
930-934.2006)
Association of a bitter taste receptor mutation with
Balkan Endemic Nephropathy (BEN).
Wooding et al. BMC Med Genet. 2012 Oct 11;
Aristolochia clematitis
….strong odds with the prediction
that carriers of functional alleles
of TAS2R43
are protected from BEN by
an ability to detect and
avoid aristolochic acid exposure
Un recentissimo lavoro mostra una stretta associazione tra un aplotipo caratterizzato
da tre polimorfismi di TAS2R, ed un’alterata omeostasi del glucosio e dell’insulina
e che uno dei tre polimorfismi annulla la funzionalità del recettore codificato dal gene
TAS2R9 (Dotson C. D., 2008
We looked at bitter taste gene
polymorphism in a group of elder people
Chromosome7:
1370bp
390bp 876bp
18826637bp
266bp
15771bp
11664bp
182366bp
640bp
101bp
38191bp
1208195bp
1503bp
220241bp
191bp
33679bp
Chromosome12: 10844100..11231900
7857bp
1201bp
2451bp
126866bp
45610bp
1641bp
1592bp 644bp 31656bp
169bp 9796bp 715bp
885bp
30005bp
67bp
71876bp
52869bp
Bitter taste receptor polymorphisms and human aging. Campa D, et al. PLoS One. 2012;7(11)
TAS2R16 Genotype
p= 0.0008
Frequency
Age quartiles
87
86
85
Age
rs978739
84
83
82
81
A/A
A/G G/G
TAS2R16 rs6466849
220
210
A/A A/G
G/G
200
190
180
Total_cholesterol
Male
Analysis of Variance for
Total_cholesterol Female
------------------------------------------------------------------------------Source
Sum of Squares
Df
Mean Square
F-Ratio
PValue
------------------------------------------------------------------------------COVARIATES
Age
23613,7
1
23613,7
13,23
0,0003
MAIN EFFECTS
A:Sex
62835,2
1
62835,2
35,21
0,0000
B:TAS2R16 rs 64668
11334,8
1
11334,8
6,35
0,0120
INTERACTIONS
AB
72,8928
1
72,8928
0,04
TAS2R46 and BMI
rs 2708380
28
27
BMI
26
25
24
χ2=17.23
p= 0.0085
A/A
A/T
T/T
Association between TAS2R38 gene polymorphisms and colorectal cancer risk:
a case-control study in two independent populations of Caucasian origin.
PLoS One. 2011;6(6): Carrai M, et al.
(OR = 1.34, 95% CI 1.12–1.61; Pvalue = 0.001)
600
500
400
800
300
600
200
400
100
200
0
0
Germany
Czechoslovakia
ITALY
Gut bitter taste receptor signalling induces ABCB1 through a mechanism involving
CCK.
Jeon TI et al. Biochem J. 2011 Aug 15;438(1):33-7
GPL-1
aumentando la secrezione di insulina da parte delle cellule beta del pancreas;
diminuendo la secrezione di glucagone (antagonista dell'insulina) da parte delle cellule alfa del pancreas;
rallentando la motilità e dunque lo svuotamento gastrico (rendendo più "soft" la curva glicemica postprandiale) e diminuendo l'appetito.
GPI decrease the secretion of stomach acid to protect the small intestine from acid damage, reduce the rate at which food is
transferred through the stomach, and inhibit the GI motility and secretion of acid
Bitter taste receptors on airway smooth muscle bronchodilate by
localized calcium signaling and reverse obstruction.
Deshpande DA, et al. Nat Med. 2010 Nov;16(11)
T2R38 taste receptor polymorphisms underlie
susceptibility to upper respiratory infection.
Lee RJ, et all. J Clin Invest.
2012 Nov 1;122(11):4145-59
Receptor activation regulates calcium-dependent NO production, resulting in stimulation of mucociliary clearance
and direct antibacterial effects, polymorphisms of the TAS2R38 gene were linked to the ability of upper respiratory
cells to clear and kill bacteria. Lastly, TAS2R38 genotype correlated with human sinonasal gram-negative bacterial
infection. These data suggest that T2R38 is an upper airway sentinel in innate defense and that genetic variation
contributes to individual differences in susceptibility to respiratory infection.
Bitter taste receptors in innate immune defense.AHLs produced by P. aeruginosa are
sensed by T2R38, activating Ca2+ signaling, leading to increased ciliary beat frequency,
NO production, and bacterial killing. This process prevents colonization of the airway.
Individuals harboring the inactive AVI allele are at greater risk of infection
Prince A. The bitter taste of infection J Clin Invest. 2012 Nov 1;122(11):3847-9
Figure 2. QRT-PCR for TAS2R46 on human MSC after differentiation into the adipocyte, osteocyte,
and chondrocyte lineages, n = 3 donors with 3 technical replicates each.
Lund TC, Kobs AJ, Kramer A, Nyquist M, et al. (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have
Chemosensory Capacity via Bitter Taste Receptor Expression. PLoS ONE 8(3): e58945. doi:10.1371/journal.pone.0058945
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058945
?
?
?
?
?
?
Figure 6. Human vascular smooth muscle cells express hTAS2R46 and are stimulated by
denatonium.
Lund TC, Kobs AJ, Kramer A, Nyquist M, et al. (2013) Bone Marrow Stromal and Vascular Smooth Muscle Cells Have
Chemosensory Capacity via Bitter Taste Receptor Expression. PLoS ONE 8(3): e58945. doi:10.1371/journal.pone.0058945
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0058945
Spatiotemporal characterization of bitter-tastant-evoked calcium responses in mouse male
germ cells: traces of calcium responses from acrosome (A), midpiece (M) and principal piece
(P) of a spermatid (left) and epididymal sperm (right) to 200 µM bitter-tastant mixture (BTM) or
individual bitter tastants: procainamide, denatonium, PTC, PROP and cycloheximide.
Xu J et al. Mol. Hum. Reprod. 2013;19:17-28
© The Author 2012. Published by Oxford University Press on behalf of the European Society of
Human Reproduction and Embryology. All rights reserved. For Permissions, please email:
[email protected]
Taste perception: from the tongue to the testis. Li F. Mol
Hum Reprod. 2013 Jun;19(6):349-60. doi: 10.1093/molehr/gat009
C Human testis
1-3 TAS2R14
4-6 TAS2R16
7-9 TAS2R38
Ectopic expression of taste and olfactory receptor genes
Expression profile of ectopic olfactory receptors determined by deep sequencing.
Flegel C, et al. PLoS One. 2013;8(2):e55368.
Expression of Tas1 taste
receptors in mammalian
spermatozoa:
functional role of Tas1r1
in regulating
basal Ca²⁺ and cAMP
concentrations in
spermatozoa.
Meyer D, et al. PLoS One. 2012;7(2)
Bacco…
Tabacco… e…Cerere
….riducono l’uomo in cenere,
ma quanto è dovuto al gusto?
Association between TAS2R38 genotypes and BMI
BMI
Frequency
40
1
2
3
30
20
10
0
C/C
C/G
G/G
Genotipes
N.A.
umo
ed Alcool
chi2 = 22,2
60
frequency
50
40
30
20
10
0
No sapore
Sì sapore
Abitudin
No fum
O fumo
Fumo &
Abitudini alimentari e TAS2R38
Vegetables
Verdure
0dislike
1like
80
F
r 60
e
q
u 40
e
n 20
z
a
0
C/C1
2
C/G
Chi quadro = 0,58
p=0,74
3
G/G
1
C/C
2
C/G
3
G/G
genotipo
Cabbage:
Cavolo
0dislike
1Gradito
50
F
r
e
q
u
e
n
z
a
40
C/C1
30
C/G2
20
Chi quadro =5,31
p=0,0703
10
0
1
C/C
2
C/G
genotipo
3
G/G
3
G/G
Food choice and TAS2R38 polymorphism
Garlic
Aglio
0Dislike
1like
50
F
r
e
q
u
e
n
z
a
40
C/C1
30
2
20
C/G
Chi quadro =2,30
p=0,31
10
3
G/G
0
1
C/C
2
C/G
3
G/G
genotipo
Onion
Cipolla
0dislike
1like
60
F
r
e
q
u
e
n
z
a
50
40
30
C/C1
C/G2
20
Chi quadro =1,95
p=0,37
10
0
1
C/C
2
C/G
genotipo
3
G/G
3
G/G
L'AMARO DEL PTC
CORRELA CON L'AMARO
DEL VINO???
INTENSITA'
DEL
SAPORE
AMARO
Valpolicella
Classico
Pinot Noir
L'Epayrie
Individual variability in wine
perception
1,5
1,4
1,3
1,2
1,1
Femmine
Masc hi
Genere
Preferenza Vino Bianco Genotipo X Genere
Grado preferenza
Grado preferenza
Preferenza vino bianco e genere
2,3
Genere
Femmine
Masc hi
2
1,7
1,4
1,1
0,8
PAV/PAV
PAV/AVI
AVI/AVI
1,8
1,6
1,4
1,2
1
Femmine
Masc hi
Genere
Preferenza Vino Rosso Genotipo X Genere
Grado preferenza
Grado preferenza
Preferenza vino rosso e genere
2,3
Genere
Femmine
Masc hi
2
1,7
1,4
Super taster
Non taster
1,1
0,8
PAV/PAV
PAV/AVI
AVI/AVI
Acknowledgements
Prof.Giuseppe Passarino
Calabria University
Prof.Roberto Barale
Departiment of
Biology
Pisa University
Dott.Fabio Caradonna
Genomic Epidemiology
Group, German Cancer
Research Center (DKFZ);
Dott.Federico Canzian
Palermo University
Maura Carrai- Pisa University
Dott.Daniele Campa