Obesity
Conditions
Keywords
Precision medicine, nutrigenomics, microbiome, obesity, diet
Brief summary
The main objective of this project is to apply a precision medicine approach to try to explain the intra-individual variability of the response to different weight loss approaches: a balanced hypocaloric diet in macronutrients (MedDiet), a very low carbohydrate diet (KetoDiet) and an intermittent fasting (IF) approach, and try to establish in a personalized manner with the individual variability in genetics, metabolites, intestinal microbiome, and environmental factors the best dietary strategy for weight loss. As secondary objectives the investigators pretend to O1: To analyze whether individual variability in genetics, epigenetics, intestinal microbiome, and environmental factors determine the changes in insulin resistance, blood pressure, lipid levels and NASH markers after three different dietary interventions. O2: To analyze whether individual variability in genetics, epigenetics, intestinal microbiome, and environmental factors determine the changes in the body composition and the different ratio of free-fat/ fat mass loss after three different dietary interventions. O3: To determine the most effective intervention to increase the loss of fat mass, preserve the free-fat mass and trigger a better metabolic profile. O4: To follow-up changes in gut microbiota and DNA methylation after each of the cross-over dietary interventions. O5: To evaluate the transcriptional response of adipose tissue and elucidate its predictive value for the body-composition changes in patients subjected to the different dietary interventions. O6: To evaluate the influence of D-ß-hydroxybutyrate as well as other short-chain acyl-CoA precursor metabolites in human adipocytes lipolysis by in vitro experimentation and elucidate the influence of metabolite-sensitive histone modifications in the shaping of adipose transcriptional program and lipolysis sensitivity. O7: To develop a machine learning algorithm based on genetics, epigenetics, intestinal microbiome, and environmental factors for the prediction of the best dietary approach for weight loss in a personalized manner. To try to respond to these objectives, the investigators will apply two models: a randomized cross-over study testing three different dietary weight-loss interventions: MedDiet, KetoDiet, and IF with wash-out periods before each intervention.
Detailed description
The main objective of this project is to apply a precision medicine approach to try to explain the intra-individual variability of the response to different weight loss approaches: a balanced hypocaloric diet in macronutrients (MedDiet), a very low carbohydrate diet (KetoDiet) and an intermittent fasting (IF) approach, and try to establish in a personalized manner with the individual variability in genetics, metabolites, intestinal microbiome, and environmental factors the best dietary strategy for weight loss. As secondary objectives the investigators pretend to O1: To analyze whether individual variability in genetics, epigenetics, intestinal microbiome, and environmental factors determine the changes in insulin resistance, blood pressure, lipid levels and NASH markers after three different dietary interventions. O2: To analyze whether individual variability in genetics, epigenetics, intestinal microbiome, and environmental factors determine the changes in the body composition and the different ratio of free-fat/ fat mass loss after three different dietary interventions. O3: To determine the most effective intervention to increase the loss of fat mass, preserve the free-fat mass and trigger a better metabolic profile. O4: To follow-up changes in gut microbiota and DNA methylation after each of the cross-over dietary interventions. O5: To evaluate the transcriptional response of adipose tissue and elucidate its predictive value for the body-composition changes in patients subjected to the different dietary interventions. O6: To evaluate the influence of D-ß-hydroxybutyrate as well as other short-chain acyl-CoA precursor metabolites in human adipocytes lipolysis by in vitro experimentation and elucidate the influence of metabolite-sensitive histone modifications in the shaping of adipose transcriptional program and lipolysis sensitivity. O7: To develop a machine learning algorithm based on genetics, epigenetics, intestinal microbiome, and environmental factors for the prediction of the best dietary approach for weight loss in a personalized manner. To try to respond to these objectives, the investigators will apply two models: a randomized cross-over study testing three different dietary weight-loss interventions: MedDiet, KetoDiet, and IF with wash-out periods before each intervention in patients with obesity; and a second cellular approach with adipose tissue from the patients as well as with commercial cells.
Interventions
OTHERMedDiet Arm
A balanced hypocaloric diet in macronutrients (MedDiet)
OTHERKetoDiet Arm
A very low carbohydrate diet (KetoDiet).
OTHERIF Arm
An intermittent fasting (IF) approach
Sponsors
Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
A randomized cross-over study testing three different dietary weight-loss interventions
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Participants aged ≥ 18 and \<70 years old who were derived to the obesity-management unit of the Endocrinology and Nutrition Unit of the Virgen de la Victoria Hospital (Málaga). * BMI between 35 and 45 kg/m2.
Exclusion criteria
* Pregnant or lactating * Following a prescribed diet for any reason in the past 3 months * Celiac disease, Crohn's disease or any condition altering nutritional requirements. * Allergies or food intolerances, as well as antibiotics treatment or usual probiotics intake.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in body weight after each intervention | From baseline to 1 month | Weight in kg |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in lipid profile (triglycerides) | From baseline to 1 month | Measured in mg/dl |
| Changes in lipid profile (cholesterol) | From baseline to 1 month | Measured in mg/dl |
| Changes in the degree of ketosis | From baseline to 1 month | Measured in mmol/l |
| Changes in gut microbiota | From baseline to 1 month | Change from baseline in 16S rRNA amplicons after 1 month |
| Changes in body composition and in the ratio of free-fat / fat mass loss after the three different dietary interventions. | From baseline to 1 month | Ratio in % |
| Changes in the degree of insulin resistance. | From baseline to 1 month | Measured by the HOMA-IR ratio |
| DNA methylation. | From baseline to 1 month | Measured by a Methylation Array of the whole genome interrogating 850000 CpGs. |
| Changes in the diastolic blood pressure | From baseline to 1 month | Blood pressure measured in millimeters of mercury |
| Changes in the punctuation in neurocognitive test - Trailmaking Test (A - B) | From baseline to 1 month | Trailmaking Test (A - B) allows evaluating visual search speed, working memory, motor skills, visual-spatial sequencing, sustained attention, divided attention and mental flexibility (time: reduction in seconds) |
| Changes in the punctuation in neurocognitive test - Stroop | From baseline to 1 month | Stroop measures selective attention and inhibitory control. (increasing scores) |
| Changes in the punctuation in neurocognitive test - WAISspan | From baseline to 1 month | Letters and numbers from the WAISspan for working memory, concentration, auditory sequencing and executive attention. (time: reduction in seconds) |
| Changes in the punctuation in neurocognitive test - UPPS-P | From baseline to 1 month | * Trailmaking Test (A - B) allows evaluating visual search speed, working memory, motor skills, visual-spatial sequencing, sustained attention, divided attention and mental flexibility (time: reduction in seconds) * Stroop: Measures selective attention and inhibitory control. (increasing scores) * Letters and numbers from the WAISspan for working memory, concentration, auditory sequencing and executive attention. (time: reduction in seconds) * UPPS-P: Impulse BehaviorScale (Cyders et al. 2007; validated in Spanish by Candido et al, 2012). Self- administered scale that evaluates impulsivity. Scale of items using a 4-point likert scale (min 59 /max 136 points). |
| Changes in the systolic blood pressure | From baseline to 1 month | Blood pressure measured in millimeters of mercury |
Countries
Spain
Contacts
Primary ContactIsabel Moreno Indias, PhD.
Backup ContactFranscisco J. Tinahones, MD, PhD.
Outcome results
None listed