An obesity-associated risk allele within the FTO gene affects human brain activity for areas important for emotion, impulse control and reward in response to food images.

TLDR: The results suggest that the two genotypes are associated with differential neural processing of food images, which may influence weight status through diminished impulse control and reward processing.

Abstract: Understanding how genetics influences obesity, brain activity and eating behaviour will add important insight for developing strategies for weight-loss treatment, as obesity may stem from different causes and as individual feeding behaviour may depend on genetic differences. To this end, we examined how an obesity risk allele for the FTO gene affects brain activity in response to food images of different caloric content via functional magnetic resonance imaging (fMRI). Thirty participants homozygous for the rs9939609 single nucleotide polymorphism were shown images of low- or high-calorie food while brain activity was measured via fMRI. In a whole-brain analysis, we found that people with the FTO risk allele genotype (AA) had increased activity compared with the non-risk (TT) genotype in the posterior cingulate, cuneus, precuneus and putamen. Moreover, higher body mass index in the AA genotype was associated with reduced activity to food images in areas important for emotion (cingulate cortex), but also in areas important for impulse control (frontal gyri and lentiform nucleus). Lastly, we corroborate our findings with behavioural scales for the behavioural inhibition and activation systems. Our results suggest that the two genotypes are associated with differential neural processing of food images, which may influence weight status through diminished impulse control and reward processing.

Figures

Figure 1. Participants homozygous for the FTO risk-allele (rs9939609) have increased 541 brain activity in response to high- and low-calorie food images. 13 participants 542 homozygous for the FTO risk allele (A) and 17 for the non-risk allele (T) were shown images 543 of either low-calorie (LC), high-calorie (HC) food, or control while brain activations were 544 measured via fMRI. A whole-brain, between-groups comparison tested the neural response to 545 foods of different caloric content (HC versus LC contrast) using total brain volume (TBV) 546 and body-mass index (BMI) as covariates of no interest. Greater activity was found in four 547 clusters for participants homozygous for the risk allele (A) compared to the normal allele (T). 548 A) Axial brain slices showing significant clusters. Exact MNI z-coordinate given below 549 slices in white numbers, and t-statistics indicated by color-coded scale bar (critical t = 3.5). 550 B) A region of interest analysis found a significant cluster within the putamen after a small-551 volumes correction. 552

Full text

Wiemerslage, L, Nilsson, EK, Solstrand Dahlberg, L, Ence-Eriksson, F, Castillo,
S, Larsen, AL, Bylund, SBA, Hogenkamp, PS, Olivo, G, Bandstein, M, Titova,
OE, Larsson, E-M, Benedict, C, Brooks, SJ and Schiöth, HB
An obesity-associated risk allele within the FTO gene affects human brain
activity for areas important for emotion, impulse control and reward in
response to food images.
http://researchonline.ljmu.ac.uk/id/eprint/9287/
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Citation (please note it is advisable to refer to the publisher’s version if you
intend to cite from this work)
Wiemerslage, L, Nilsson, EK, Solstrand Dahlberg, L, Ence-Eriksson, F,
Castillo, S, Larsen, AL, Bylund, SBA, Hogenkamp, PS, Olivo, G, Bandstein,
M, Titova, OE, Larsson, E-M, Benedict, C, Brooks, SJ and Schiöth, HB (2016)
An obesity-associated risk allele within the FTO gene affects human brain
LJMU Research Online

http://researchonline.ljmu.ac.uk/

FTO Associated Brain Activity 1
Title 1
An obesity-associated risk allele within the FTO gene affects brain activity for areas 2
important for emotion, impulse control, and reward in response to food images. 3
4
Running Title 5
FTO Associated Brain Activity 6
7
Author names and affiliation 8
Lyle Wiemerslage*
§
, Emil K Nilsson
§
, Linda Solstrand Dahlberg
§
, Fia Ence-Eriksson
§
, 9
Sandra Castillo
§
, Anna L Larsen
§
, Simon BA Bylund
§
, Pleunie S Hogenkamp
§
, Gaia 10
Olivo
§
, Marcus Bandstein
§
, Olga E Titova
§
, Elna-Marie Larsson
┼
, Christian Benedict
§
, 11
Samantha J Brooks
╪
, Helgi B Schiöth
§
12
13
Uppsala University § 14
Department of Neuroscience, Functional Pharmacology 15
Biomedicinska Centrum (BMC) 16
Husargatan 3, Box 593 17
751 24 Uppsala, Sweden 18
19
Section of Neuroradiology ┼ 20
Department of Radiology, Uppsala University 21
Akademiska Sjukhuset 22
751 85 Uppsala, Sweden 23
24
University of Cape Town ╪ 25
Department of Psychiatry 26
Old Groote Schuur Hospital 27
J2 Building 28
Anzio Road 29
Observatory, Cape Town, South Africa. 30
31
Corresponding author 32
Uppsala University * 33
Department of Neuroscience, Functional Pharmacology 34
Biomedicinska Centrum (BMC) 35

FTO Associated Brain Activity 2
Husargatan 3, Box 593 36
751 24 Uppsala, Sweden 37
lyle.wiemerslage@neuro.uu.se 38
39
Number of: 40
• Figures = 3 41
• Tables = 1 42
• Words: 43
o Abstract = 197 44
o Introduction = 565 45
o Entire Manuscript (excluding references and figure legends) = 3,972 46
47
Keywords: 48
FTO, fMRI, SNP, obesity, food 49
50
Conflict of Interest: 51
The authors declare no conflicts of interest. 52

FTO Associated Brain Activity 3
ABSTRACT 53
Understanding how genetics influences obesity, brain activity, and eating behavior will 54
add important insight for developing strategies for weight-loss treatment, as obesity may stem 55
from different causes and as individual feeding behavior may depend on genetic differences. 56
To this end, we examined how an obesity risk-allele for the FTO gene affects brain activity in 57
response to food images of different caloric content via fMRI. 30 participants homozygous 58
for the rs9939609 single nucleotide polymorphism were shown images of low- or high-calorie 59
food while brain activity was measured via fMRI. In a whole-brain analysis, we found that 60
people with the FTO risk-allele genotype (AA) had increased activity than the non-risk (TT) 61
genotype in the posterior cingulate, cuneus, precuneus, and putamen. Moreover, higher BMI 62
in the AA genotype was associated with reduced activity to food images in areas important for 63
emotion (cingulate cortex), but also in areas important for impulse control (frontal gyri and 64
lentiform nucleus). Lastly, we corroborate our findings with behavioral scales for the 65
behavioral inhibition and activation systems (BIS/BAS). Our results suggest that the two 66
genotypes are associated with differential neural processing of food images, which may 67
influence weight status through diminished impulse control and reward processing. 68
69
Keywords: 70
fMRI, FTO, SNP, BMI, food images, obesity 71

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56 To this end, the authors examined how an obesity risk-allele for the FTO gene affects brain activity in 57 response to food images of different caloric content via fMRI. Their results suggest that the two 66 genotypes are associated with differential neural processing of food images, which may 67 influence weight status through diminished impulse control and reward processing.