Gut Microbiota, Mitochondrial Function and Metabolic Health in Obesity

NCT06279780 | Completed

• 1 other identifier: PI18/00932
• Study Type: interventional
• Target: 109
• Locations: 1 country
• Sites: 1

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.

Conditions

Obesity Adult Onset

Keywords

metabolic syndrome; Very low-calorie diet; Microbiota; oxidative stress; Inflammation

Outcome Measures

Primary Outcomes (2)

• Analyze the changes in the diversity of the intestinal microbiota after dietetic intervention.

  To assess the alpha-diversity of the intestinal microbiota, defined as the average diversity of species in an ecosystem, the Shannon index will be used. The results are interpreted as follows: values less than 2 are considered low in diversity and values greater than 3 are high in species diversity.

  5 years

• Evaluate the differences in the diversity of the intestinal microbiota depending on whether patients present metabolically healthy obesity (MHO) or metabolically unhealthy obesity (MUHO).

  To asses the differences in alpha-diversity of the intestinal microbiota in both groups, it will be evaluated whether there are significant differences between the Shannon indices of the two groups. The classification of patients between MHO and MUHO will be carried out using the following criteria: MUHO will be considered when patients with obesity present ≥2 metabolic abnormalities, and MHO with ≤1 metabolic abnormalities; the following cardiovascular risk factors are considered metabolic abnormalities: elevated blood pressure (defined as either SBP ≥130 mm Hg, DBP ≥85 mm Hg, or treatment with antihypertensive medications), elevated triglycerides (as fasting triglyceride concentration ≥1.7 mmol/l), low HDL-C levels (defined as HDL-C \<1.04 mmol/l, in men, \<1.29 mmol/l/l in women, or treatment with lipid-lowering medications), dysglycemia (fasting plasma glucose 5.6 to 6.9 mmol/l, and/or and insulin resistance as HOMA-IR \>3.8).

  5 years

Secondary Outcomes (15)

• Evaluate significant changes in body fat mass percentage after the dietetic intervention.

  2 years

• Assess significant changes in high-sensitivity C-reactive protein (hs-CRP) as an inflammatory parameter after the dietetic intervention.

  2 years

• Evaluate significant changes in C3 protein as an inflammatory parameter after the dietetic intervention.

  2 years

• Assess significant changes in plasmatic homocysteine as an inflammatory parameter after the dietetic intervention.

  2 years

• Evaluate significant changes in interleukin 1-beta (IL-1B) levels as a pro-inflammatory molecule after the dietetic intervention.

  2 years

Study Arms (1)

Very low-calorie diet Intervention

EXPERIMENTAL

Dietary Supplement: very low-calorie diet

Interventions

very low-calorie diet DIETARY_SUPPLEMENT

Subjects undergo two cycles of a very-low-calorie diet (VLCD) for 6 weeks each, alternating with a hypocaloric diet (12 weeks). The dietetic intervention consists of a VLCD using a liquid formula (Optisource Plus, Nestlé S.A., Vevey, Switzerland), providing 52.8 g protein, 75.0 g carbohydrates, 13.5 g fat, 11.4 g fiber, and essential vitamins and minerals based on Recommended Dietary Allowances (RDA). This formula supplies 2738 kJ/day (654 kcal/day), replacing the participants' three daily meals. Following this and before the second VLCD cycle, a dietician performs an individualized nutritional assessment to calculate the resting energy expenditure, and personalized hypocaloric diets were prepared, reducing 500 kcal for each individual on their daily caloric expenditure, maintaining the recommended intake of each of the macronutrients (55% carbohydrates, 30% fats and 15% proteins) for 12-weeks.

Also known as: VLCD

Very low-calorie diet Intervention

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Celia Bañuls: lead
• Instituto de Salud Carlos III: collaborator

Study Sites (1)

FISABIO

Valencia, Valencia, 46020, Spain

Location

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MeSH Terms

Conditions

Metabolic Syndrome; Inflammation

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 2, 2024
• First Posted: February 28, 2024
• Study Start: January 1, 2019
• Primary Completion: December 31, 2023
• Study Completion: August 31, 2024
• Last Updated: February 27, 2025

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)