Adipose Tissue Gene Expression and Metabolomics Links to the Gut Microbiome-brain Axis

Recruiting

• Conditions: Obesity

• Registration Number: NCT06869941
• Lead Sponsor: Institut d'Investigació Biomèdica de Girona Dr. Josep Trueta

Brief Summary

This study aims to understand how adipose tissue (fat) and the gut microbiota (the bacteria in the gut) may influence brain function and cognition. It has been observed that changes in adipose tissue in animals such as mice and Drosophila (a type of insect) affect memory and other brain functions. Additionally, it is believed that the gut microbiota also plays an important role in cognition.

This study will explore how gene expression in adipose tissue, blood metabolites, and the gut microbiota are related to cognitive function, such as memory and thinking, in individuals with and without obesity. The investigation will also assess whether these factors can predict changes in the brain over time and how they influence sleep, physical activity, and blood sugar regulation.

Advanced technologies will be used to analyze samples of tissue, blood, and microbiota, with the goal of identifying new mechanisms through which obesity affects the brain. This research may contribute to the development of new diagnostic and therapeutic strategies for cognitive problems in individuals with obesity.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-03
• Study First Submitted: 2025-03-05
• Study First Submitted QC: 2025-03-10
• Study First Posted: 2025-03-11
• Study Start: 2025-05
• Last Update Submitted: 2025-05-09
• Last Update Posted: 2025-05-14
• Primary Completion: 2028-04
• Study Completion: 2028-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Men and women >20 years old.
• Scheduled for surgical intervention to extract adipose tissue.
• Signed informed consent for study participation.

Exclusion Criteria

• Not meeting inclusion criteria.
• Non-obesity-related systemic diseases (cancer, severe kidney/liver disease).
• Systemic diseases with intrinsic inflammation (rheumatoid arthritis, Crohn's disease, asthma, chronic infections (HIV/tuberculosis)) or any type of infectious disease.
• Pregnant/breastfeeding women.
• Persons under legal/administrative restrictions.
• Those with infection symptoms in the past month.
• Use of antibiotics/antifungals/antivirals (previous 3 months).
• Chronic steroidal/anti-inflammatory drug use.
• Major psychiatric history.
• Excessive alcohol intake, acute or chronic (>40g/day (women), >80g/day (men)) or drug abuse.
• Immunosuppressants treatment.
• Participants with severe eating disorders.
• Serum liver enzymes (GOT, GPT) above twice the upper limit of normal. Obvious signs or symptoms of liver disease, acute or chronic hepatitis.
• History of iron balance disorders (e.g., genetic hemochromatosis, hemosiderosis from any cause, atransferrinemia, paroxysmal nocturnal hemoglobinuria).
• Creatinine greater than 1.2 and glomerular filtration rate below 40.
• Current treatment for malignant neoplasia, other than basal cell or squamous cell skin cancer.
• Heart disease classified as class III or IV, known ischemic cardiovascular disease.
• Renal failure, history of kidney transplant, or current dialysis treatment.
• Chronic constipation (bowel movement frequency ≥ 7 days) .

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Glycemic variability	36 month	Mean and standard deviation of glucose measures in mg/dL using a CGM 10 days.
The glycaemic risk measured with the low blood glucose index (LBGI)	36 months	Low blood glucose index (LBGI) is a parameter that quantifies the risk of glycaemic.
The percentage of time in glucose target range (glucose level 100mg/dl-125mg/dl)	36 months
The glycaemic variability measured with mean amplitude of glycaemic excursions (MAGE)	36 months	measured in mg/dl
Minutes light sleep	36 months	Mean and standard deviation of minutes' light sleep measures by activity and sleep tracker device.
Minutes deep sleep	36 months	Mean and standard deviation of minutes' deep sleep measures by activity and sleep tracker device.
Minutes rapid eye movement (REM)	36 months	Mean and standard deviation of minutes REM measures by activity and sleep tracker device.

Secondary Outcome Measures

Name	Time	Method
Behavioural inhibition	36 months	It will be measured by Sensitivity to Punishment and Sensitivity to Reward (SPSRQ). The scale of Sensitivity to Punishment is related to the behavioural inhibition system. It is made up of two subscales of 24 items each. For each subscale, the minimum score is 0 and the maximum score is 24, with higher scores indicating greater sensitivity to punishment or reward, respectively.
Behavioural activation	36 months	It will be measured by Sensitivity to Punishment and Sensitivity to Reward (SPSRQ). The reward sensitivity scale is related to the behavioural activation system. The questionnaire consists of two subscales of 24 items each. Each subscale ranges from 0 (minimum) to 24 (maximum), where a higher score indicates greater sensitivity to reward or punishment, respectively.
Visoconstructive function	36 months	It will be measured by Rey-Osterrieth Complex Figure. Minimum/maximum scale values (0-36), where 36 is a better visoconstructive function.
Selective and alternating attention	36 months	It will be measured by Trail making test (Part A and B).
Semantic verbal fluency	36 months	It will be measured by Animals test. The person must name as many animals as possible in 1 minute. The result is corrected by standard scores, according to age and level of education.
Facial recognition	36 months	It will be measured by Picture of Facial Recognition Test (POFA).
Attention and working memory	36 months	It will be measured by the Digits subtest of the Wechsler Adult Intelligence Scale - Fourth Edition (WAIS-IV). This subtest includes two parts: Digits Forward (measuring attention) and Digits Backward (measuring working memory). The total raw score ranges from 0 (minimum) to 30 (maximum), with higher scores indicating better attention and working memory capacity.
Inhibition	36 months	It will be measured by Stroop Color-Word Test.
Phonemic verbal fluency	36 months	It will be measured by PMR.
Emotion recognition	36 months	It will be measured by Benton Facial Recognition Test (BFRT). This test evaluates the recognition of the five basic emotions: happiness, sadness, surprise, disgust, and anger.
Binge eating disorder	36 months	It will be measured by Binge Eating Scale (BES). The BES is one of the most widely used measures to assess binge eating disorder symptomatology. The BES score ranges from 0 to 46 and its cut-off point is greater than or equal to 27. Subjects with scores higher than 27 are more likely to suffer from binge eating disorder.
Audioverbal memory	36 months	It will be measured by California Verbal Learning Test (CVLT). Minimum/maximum scale values (0-16), where 16 is a better audioverbal memory.
Effect on gut microbiota	36 months	Gut microbiota will be analysed by metagenomics and metabolomics.
Visual memory	36 months	It will be measured by Rey-Osterrieth Complex Figure. Minimum/maximum scale values (0-36), where 36 is a better visual memory.
Depressive symptomatology	36 months	It will be measured by Patient Health Questionnaire-9 (PHQ-9). Minimum/maximum scale values (0-27), where ≥ 20 is severe depression.
Impulsivity	36 months	It will be measured by Impulsive Behaviour Scale (UPPS-P). The test evaluates: Negative urgency (tendency to act rashly under extreme negative emotions), Lack of Premeditation (tendency to act without thinking), Lack of Perseverance (inability to remain focused on a task) and Sensation Seeking (tendency to seek out novel and thrilling experiences). All items are rated on a four point scale from 1 (strongly agree) to 4 (strongly disagree).
Food Addiction	36 months	It will be measured by Yale Food Addiction Scale. It is a symptom score from 0-11, based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria, for substance dependence. Food addiction is diagnosed if ≥3 symptoms are reported.
Anxiety state	36 months	It will be measured by State-Trate Anxiety Inventory (STAI). This questionnaire evaluates state anxiety (S) and trait anxiety (R) through 20 items each, with a likert-type response scale of four alternatives. In the case of state anxiety, the scale goes from 0 (not at all) to 3 (a lot), while for trait anxiety it goes from 0 (almost never) to 3 (almost always). The higher the score, the greater the anxiety in both concepts.
Effect on brain structure	36 months	Brain structure will be assessed using magnetic resonance imaging.
Diffusion Tensor Imaging brain sequences	36 months	Diffusion Tensor Imaging was acquired at 1.5 T (Philips ingenia) using a single-shot spin echo sequence with echo-planar imaging (EPI), 50 contiguous slices, voxel size 2x2x2.5 mm3, TE/TR of 72/3581 ms/ms, a diffusion-weighting factor b = 800 s/mm2 and diffusion encoding along 32 directions.
Brain iron accumulation	36 months	It will be assessed using magnetic resonance imaging using (R2\*)
Resting-state functional brain sequences	36 months	It will be assessed using magnetic resonance imaging (T2\*-weighted echo-planar imaging). T2 \* relaxation data will be acquired with a multi-echo gradient sequence with 10 equidistant echoes (first echo = 4.6ms; echo spacing = 4.6ms; repetition time = 1300ms). The value of T2 \* will be calculated by adjusting the simple exponential terms for the signal decay of the respective echo time values.
Insulin resistance	36 months	It will be measured by HOMA
Markers of chronic inflammation (C-reactive protein, IL-6, adiponectin and soluble, tumour necrosis factor-α receptor fractions)	36 months	Enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction (qPCR)
Glycosylated haemoglobin (HbA1c) value	36 months	Glycosylated haemoglobin (HbA1c) in % or mmol/mol
The percentage of time in hyperglycaemia (glucose level above 250 mg/dl)	36 months
The percentage of time in hypoglycaemia (glucose level below 70mg/dl)	36 months
The percentage of time in glucose range (glucose level below 100 mg/dl)	36 months
The percentage of time in glucose range (glucose level between 126-139 mg/dl)	36 months
The percentage of time in glucose range (glucose level between 140-199 mg/dl)	36 months
The percentage of time in glucose range (glucose level above 200 mg/dl)	36 months
Burned calories	36 months	Mean and standard deviation of burned calories measures by activity and sleep tracker device.
Steps Mean and standard deviation of steps measures by activity and sleep tracker device.	36 months	The mean and standard deviation of steps refer to the average number of steps taken by a participant and how much those steps vary from the average, as measured by an activity and sleep tracker device. The mean is the average, while the standard deviation shows the variation or consistency in step count.
Distance Mean and standard deviation of distance measures by activity and sleep tracker device.	36 months
Minutes null activity	36 months	Mean and standard deviation of minutes' null activity measures by activity and sleep
Minutes slight activity	36 months	Mean and standard deviation of minutes slight activity measures by activity and sleep
Minutes mean activity	36 months	Mean and standard deviation of minutes mean activity measures by activity and sleep tracker device.
Minutes high activity	36 months	Mean and standard deviation of minutes high activity measures by activity and sleep tracker device.
Calories	36 months	Mean and standard deviation of calories measures by activity and sleep tracker device.
Minutes asleep	36 months	Mean and standard deviation of minutes asleep measures by activity and sleep tracker.
Minutes awake	36 months	Mean and standard deviation of minutes awake measures by activity and sleep tracker.
Bed time Mean and standard deviation of bed time measures by activity and sleep tracker device.	36 months
Number time awake Mean and standard deviation of number time awake measures by activity and sleep	36 months

Trial Locations

Locations (1)

Institut d'Investigació Biomèdica de Girona (IDIBGI); 🇪🇸 Girona, Spain