protocolSection identificationModule nctId: NCT06279780, orgStudyIdInfo id: PI18/00932, briefTitle: Gut Microbiota, Mitochondrial Function and Metabolic Health in Obesity, statusModule overallStatus: ACTIVE_NOT_RECRUITING, startDateStruct date: 2019-01-01, primaryCompletionDateStruct date: 2023-12-31, completionDateStruct date: 2024-08-31, studyFirstPostDateStruct date: 2024-02-28, lastUpdatePostDateStruct date: 2024-02-28, sponsorCollaboratorsModule leadSponsor name: Celia Bañuls, class: OTHER, collaborators name: Instituto de Salud Carlos III, descriptionModule briefSummary: 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., conditionsModule conditions: Obesity Adult Onset, designModule studyType: INTERVENTIONAL, phases: NA, designInfo allocation: NA, interventionModel: SINGLE_GROUP, primaryPurpose: TREATMENT, maskingInfo masking: NONE, enrollmentInfo count: 109, type: ACTUAL, armsInterventionsModule interventions name: very low-calorie diet, outcomesModule primaryOutcomes measure: Analyze the changes in the diversity of the intestinal microbiota after dietetic intervention., primaryOutcomes 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)., secondaryOutcomes measure: Evaluate significant changes in body fat mass percentage after the dietetic intervention., secondaryOutcomes measure: Assess significant changes in high-sensitivity C-reactive protein (hs-CRP) as an inflammatory parameter after the dietetic intervention., secondaryOutcomes measure: Evaluate significant changes in C3 protein as an inflammatory parameter after the dietetic intervention., secondaryOutcomes measure: Assess significant changes in plasmatic homocysteine as an inflammatory parameter after the dietetic intervention., secondaryOutcomes measure: Evaluate significant changes in interleukin 1-beta (IL-1B) levels as a pro-inflammatory molecule after the dietetic intervention., secondaryOutcomes measure: Evaluate significant changes in interleukin 6 (IL-6) levels as a pro-inflammatory molecule after the dietetic intervention., secondaryOutcomes measure: Evaluate significant changes in tumor necrosis factor alpha (TNF-alpha) levels as a pro-inflammatory molecule after the dietetic intervention., secondaryOutcomes measure: Assess significant changes in superoxide dismutase (SOD) levels after the dietetic intervention., secondaryOutcomes measure: Analyze the significant differences between metabolomic profile before and after the dietetic intervention., secondaryOutcomes measure: Evaluate if there is a significant reduction after the dietetic intervention in total ROS levels., secondaryOutcomes measure: Assess if there is a significant reduction after the dietetic intervention in glutathione levels., secondaryOutcomes measure: Analyze if there is a significant change after the dietetic intervention in total free radicals and superoxide levels., secondaryOutcomes measure: Analyze if there is a significant reduction after the dietetic intervention in mitochondrial ROS production., secondaryOutcomes measure: Evaluate if there is a significant improvement after the dietetic intervention in mitochondrial membrane potential., secondaryOutcomes measure: Analyze the proportion of subjects achieving at least 10% reduction in weight compared with baseline., eligibilityModule sex: ALL, minimumAge: 18 Years, maximumAge: 60 Years, stdAges: ADULT, contactsLocationsModule locations facility: FISABIO, city: Valencia, zip: 46020, country: Spain, geoPoint lat: 39.46975, lon: -0.37739, hasResults: False