Clinical trial NCT06279780: Gut Microbiota, Mitochondrial Function and Metabolic Health in Obesity
Official title: Effect of a Very Low-calorie Diet on Microbiota, Oxidative Stress, Inflammatory and Metabolomic Profile in Metabolically Healthy and Unhealthy Obese Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity Adult Onset
Keywords: metabolic syndrome
Very low-calorie diet
Microbiota
oxidative stress
Inflammation
Lead sponsor: Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
Sponsor class: OTHER
Collaborators: name: Instituto de Salud Carlos III
First posted: 2024-02-28
Enrollment: 109
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: It has been suggested that individuals with the condition known as metabolically healthy obesity (MHO) may not have the same increased risk of developing metabolic abnormalities as their non-metabolically healthy counterparts. In addition, to date, the identification of metabolic biomarkers and microbiota underlying the MHO state is limited. In this study, our goal is to provide insight into the underlying metabolic pathways affected by obesity. To achieve this, we will compare the metabolic profile, inflammatory parameters and mitochondrial function, as well as metabolomic analysis and differential expression of microbiota in obese patients categorized as metabolically healthy vs. non healthy. In parallel, the effect of a hypocaloric diet on obese subjects' metabolism and microbiota will be assessed to approve their use in the treatment of said disorder. Specifically, we propose an observational, clinical-basic, comparative and interventional study in a population of 80 obese (BMI\>35 kg/m2) patients clustered in two groups according to the presence or absence of altered metabolism (altered fasting glycemia, hypertension, atherogenic dyslipidemia). Anthropometric and clinical variables and biological samples (serum, plasma, peripheral blood cells and feces) will be collected for the determination of biochemical parameters (glucose, lipid and hormonal profile by enzymatic techniques) and protein-based peripheral biomarkers of mitochondrial function \[total and mitochondrial reactive oxygen species (ROS) production, mitochondrial membrane potential, glutathione levels by static cytometry\], markers of mitochondrial dynamics \[Mitofusin 1 (MFN1), Mitofusin 2 (MFN2), Mitochondrial fision protein 1 (FIS1) and Dynamin-related protein 1 (DRP1) by RT-PCR and Western Blot\], markers of inflammation \[Interleukin 6 (IL6), Tumoral necrosis factor alpha (TNFα), IL1b, adiponectin, resistin, plasminogen activator inhibitor 1 (PAI-1), Monocyte chemoattractant protein-1 (MCP-1), caspase 1 and NLRP3 by Western Blot and technology XMAP), metabolomic assay (NMR spectroscopy and PLS-DA), as well as gut microbiota content and diversity (16S rRNA, MiSeq sequencing). Finally, we will evaluate the effect of a dietary weight loss intervention on these biomarkers.


Eligibility criteria: Inclusion Criteria:

* Patients with BMI≥30kg/m2, with at least 5 years of diagnosed obesity evolution.
* Patients have had stable body weight (±2 kg) during the 3 months prior to the study.

Exclusion Criteria:

* All patients with acute or chronic inflammatory diseases, neoplasic disease, secondary causes of obesity (uncontrolled hypothyroidism, Cushing's syndrome), and established liver and kidney failure (according to transaminase levels ±2 SD of the mean and estimated glomerular filtration rate using the CKD-EPI formula \>60) will be excluded.

Primary outcomes:
measure: Analyze the changes in the diversity of the intestinal microbiota after dietetic intervention.
timeFrame: 5 years
measure: Evaluate the differences in the diversity of the intestinal microbiota depending on whether patients present metabolically healthy obesity (MHO) or metabolically unhealthy obesity (MUHO).
timeFrame: 5 years
Secondary outcomes:
measure: Evaluate significant changes in body fat mass percentage after the dietetic intervention.
timeFrame: 2 years
measure: Assess significant changes in high-sensitivity C-reactive protein (hs-CRP) as an inflammatory parameter after the dietetic intervention.
timeFrame: 2 years
measure: Evaluate significant changes in C3 protein as an inflammatory parameter after the dietetic intervention.
timeFrame: 2 years
measure: Assess significant changes in plasmatic homocysteine as an inflammatory parameter after the dietetic intervention.
timeFrame: 2 years
measure: Evaluate significant changes in interleukin 1-beta (IL-1B) levels as a pro-inflammatory molecule after the dietetic intervention.
timeFrame: 2 years
measure: Evaluate significant changes in interleukin 6 (IL-6) levels as a pro-inflammatory molecule after the dietetic intervention.
timeFrame: 2 years
measure: Evaluate significant changes in tumor necrosis factor alpha (TNF-alpha) levels as a pro-inflammatory molecule after the dietetic intervention.
timeFrame: 2 years
measure: Assess significant changes in superoxide dismutase (SOD) levels after the dietetic intervention.
timeFrame: 2 years
measure: Analyze the significant differences between metabolomic profile before and after the dietetic intervention.
timeFrame: 2 years
measure: Evaluate if there is a significant reduction after the dietetic intervention in total ROS levels.
timeFrame: 2 years
measure: Assess if there is a significant reduction after the dietetic intervention in glutathione levels.
timeFrame: 2 years
measure: Analyze if there is a significant change after the dietetic intervention in total free radicals and superoxide levels.
timeFrame: 2 years
measure: Analyze if there is a significant reduction after the dietetic intervention in mitochondrial ROS production.
timeFrame: 2 years
measure: Evaluate if there is a significant improvement after the dietetic intervention in mitochondrial membrane potential.
timeFrame: 2 years
measure: Analyze the proportion of subjects achieving at least 10% reduction in weight compared with baseline.
timeFrame: 5 years
Other outcomes:
Locations:
city: Valencia
country: Spain
facility: FISABIO
Study officials:
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