NCT06279780

Gut Microbiota, Mitochondrial Function and Metabolic Health in Obesity

Effect of a Very Low-calorie Diet on Microbiota, Oxidative Stress, Inflammatory and Metabolomic Profile in Metabolically Healthy and Unhealthy Obese Subjects

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 109 (actual)
• Sponsor: Celia Bañuls · Academic / Other
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Not accepted

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

Interventions

Type	Name	Description
DIETARY_SUPPLEMENT	very low-calorie diet	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.

Timeline

• Start date: 2019-01-01
• Primary completion: 2023-12-31
• Completion: 2024-08-31
• First posted: 2024-02-28
• Last updated: 2025-02-27

Locations

1 site across 1 country: Spain