Obesity
Conditions
Keywords
obesity, orlistat, taste perception
Brief summary
There are many substances naturally present in the mouth that may help us taste fat in food. Two of these substances (lipases and CD36) will be examined in this study. The presence of fat in food increases food tastiness, therefore people often over-eat high-fat foods and gain weight. The purpose of this study is to determine if blocking lipases and some genetic variations in the CD36 gene will make fatty food less tasty so that people eat less. Our hypothesis is that Orlistat and a particular gene will increase one's ability to detect fat.
Detailed description
1. Determine the effect of lipolysis inhibition in oral cavity on orosensory detection of fat in humans. Hypothesis: Orally applied Orlistat will increase detection thresholds of TAGs but not FFA in humans. To test this hypothesis we will measure triolein (a TAG) and oleic acid (a FFA) taste detection thresholds with a three-alternative forced-choice (3-AFC) ascending concentration method under two conditions (Orlistat day vs. Control day). To control for olfactory input, subjects will be assessed wearing noseclips. 2. Determine the effect of CD36 variants on fat taste perception in humans. Hypothesis: SNPs that associate with reduced CD36 expression will be associated with higher FFA and TAG detection thresholds To test this hypothesis we will measure triolein and oleic acid taste detection thresholds in subjects who carry of the common CD36 e-SNP rs1761667 (i.e. a SNP that significantly reduces CD36 level and has a minor allele frequency of 38-48%). We expect subjects who are at least heterozygous for the expression reducing allele to have higher triolein and oleic acid taste detection thresholds compared to non-carrier subjects.
Interventions
None listed
Sponsors
GlaxoSmithKline
Washington University School of Medicine
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
21 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Body Mass Index greater than 30 kg/m²
Exclusion criteria
* smokers or who quit smoking less than six months ago * pregnancy * breastfeeding * diabetes * taking medications that might affect taste perception * previous malabsorptive or restrictive intestinal surgery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Oleic Acid Detection Level | Ranges from 5 days after screening to several weeks, pending availablity of participant. | We will measure oleic acid detection levels as a marker of subjects' ability to detect free fatty acids. Oleic acid taste detection thresholds were separately assessed using a three-alternative forced-choice (i.e. 3-AFC) ascending concentration. |
| Triolein Detection | Ranges from 5 days after screening to several weeks, pending availablity of participant. | We will measure triolein detection levels as a marker of subjects' ability to detect triglyceride. Triolein taste detection thresholds were separately assessed using a three-alternative forced-choice (i.e. 3-AFC) ascending concentration. |
Countries
United States
Participant flow
Recruitment details
May 2010- August 2011 recruited by local posters and media advertising via the Washington University Research Participant Registry.
Pre-assignment details
40 subjects signed consent form and were screened for rs1761667 genotype and three groups (i.e., AA, AG and GG) matched in age and BMI were invited to participate on the taste test.
Participants by arm
| Arm | Count |
|---|---|
| rs1761667- AA Genotype Obese subjects carrying the CD36 genotype rs1761667, i.e. a Single Nucleotide Polymorphism that significantly reduces CD36 level | 6 |
| rs1761667-GG Genotype Obese subjects who are homozygous of CD36 genotype rs1761667-G allele. | 8 |
| rs1761667-AG Genotype Obese subjects who are heterozygous of CD36 gene rs1761667-A genotype. | 7 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Excluded due to sinus problems | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 |
| Overall Study | Screening failure | 1 | 0 | 0 |
| Overall Study | were not invited to participate on taste | 0 | 0 | 15 |
Baseline characteristics
| Characteristic | rs1761667-AG Genotype | rs1761667- AA Genotype | rs1761667-GG Genotype | Total |
|---|---|---|---|---|
| Age, Continuous | 39.6 years STANDARD_DEVIATION 6.4 | 38.7 years STANDARD_DEVIATION 14 | 39.1 years STANDARD_DEVIATION 7 | 39.1 years STANDARD_DEVIATION 8.8 |
| Sex: Female, Male Female | 6 Participants | 6 Participants | 6 Participants | 18 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Oleic Acid Detection Level
We will measure oleic acid detection levels as a marker of subjects' ability to detect free fatty acids. Oleic acid taste detection thresholds were separately assessed using a three-alternative forced-choice (i.e. 3-AFC) ascending concentration.
Time frame: Ranges from 5 days after screening to several weeks, pending availablity of participant.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rs1761667- AA Genotype | Oleic Acid Detection Level | -0.3 log10 (%W/V OLEIC ACID) | Standard Error 0.3 |
| rs1761667-GG Genotype | Oleic Acid Detection Level | -1.2 log10 (%W/V OLEIC ACID) | Standard Error 0.2 |
| rs1761667-AG Genotype | Oleic Acid Detection Level | -1.0 log10 (%W/V OLEIC ACID) | Standard Error 0.3 |
p-value: 0.05ANOVA
Primary
Triolein Detection
We will measure triolein detection levels as a marker of subjects' ability to detect triglyceride. Triolein taste detection thresholds were separately assessed using a three-alternative forced-choice (i.e. 3-AFC) ascending concentration.
Time frame: Ranges from 5 days after screening to several weeks, pending availablity of participant.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| rs1761667- AA Genotype | Triolein Detection | 0.55 log10 (%W/V TRIOLEIN) | Standard Error 0.25 |
| rs1761667-GG Genotype | Triolein Detection | -0.33 log10 (%W/V TRIOLEIN) | Standard Error 0.22 |
| rs1761667-AG Genotype | Triolein Detection | -0.04 log10 (%W/V TRIOLEIN) | Standard Error 0.23 |
p-value: 0.05ANOVA