Autophagy and Inflammasome in Obesity: Effect of Weight Loss and Potential Therapeutic Implications
- Conditions
- Obesity
- Interventions
- Procedure: Roux-en-Y gastric bypass
- Registration Number
- NCT05071391
- Lead Sponsor
- Milagros Rocha Barajas
- Brief Summary
The main aim of this project is to determine the implication of autophagy and inflammasome in the pathogenesis of obesity and related comorbidities, and to explore in depth the mechanisms associated with the activation of immune cells leading early stages of the atherosclerotic process and metabolic disease. The hypothesis of the present study is that weight loss mediated by Roux-en-Y gastric bypass (RYGB) improves the protein expression of markers of autophagy and inflammation within immune cells. Moreover, the investigators will explore the association of these mechanisms with the mitochondrial function and dynamics, Endoplasmic Reticulum (ER) stress an intracellular nutritional status of leukocytes (measured by fluorescence microscopy and western blot). Further, the potential relationship between changes in the mentioned intracellular pathways and systemic pathological mechanisms including oxidative stress, inflammation and glucose and lipid metabolism will be explored. Hence, serum carbonylated proteins, myeloperoxidase (MPO) levels, antioxidant enzymatic activities including SOD (Superoxide dismutase) and catalase, circulating cytokines, and glucose and lipid metabolism parameters will be evaluated in a cohort of obese subjects before and 12 months after RYGB intervention.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 45
- Body Mass Index (BMI) ≥ 30 kg/m^2
- duration of obesity over 5 years
- history of drug abuse
- pregnancy or lactation
- neoplastic disease
- severe renal/hepatic disease
- history of cardiovascular disease
- chronic inflammatory disease
- secondary cause for obesity (hypothyroidism, Cushing's syndrome)
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Obese Roux-en-Y gastric bypass Obese patients undergoing Roux-en-Y gastric bypass
- Primary Outcome Measures
Name Time Method Changes in the protein expression of autophagy markers in leukocytes 12 months after the RYGB intervention 12 months Relative expression of intracellular proteins related autophagy/mitophagy mechanisms (Beclin 1, ATG5, LC3II/I, NRB1, PINK1, MIEAP) assessed by western blot and normalized to the loading control protein.
Changes in the relative protein expression of inflammatory mediators in leukocytes 12 months after the RYGB intervention 12 months Relative expression of intracellular proteins related to inflammatory pathways (MCP1, NF-kB) assessed by western blot and normalized to the loading control protein.
- Secondary Outcome Measures
Name Time Method Changes in the protein expression of markers of mitochondrial dynamics and function in leukocytes 12 months after the RYGB intervention. 12 months Relative expression of proteins related to mitochondrial dynamics and function (OPA1, FIS1, MFN1, DRP1, MFN2, OXPHOS Complex, MTTFA, PGC1α, NRF1, BNIP3) assessed by western blot and normalized to the loading control protein. Changes in mitochondrial membrane potential of leukocytes after the intervention assessed by fluorescence dye TMRM.
Changes in protein carbonylation in serum 12 months after the RYGB intervention. 12 months Evaluation of carbonyl groups in serum proteins by means of immunoassay ELISA (nmol/mg protein) as a marker of systemic oxidative damage.
Effect of the RYGB on blood pressure 12 months Changes in Systolic/Diastolic Blood Pressure levels (SBP/DBP) (mmHg) measured with a sphygmomanometer
Effect of the RYGB on Triglyceride (TG) levels 12 months Changes in TG (mg/dL) of patients 12 months after the RYGB intervention, as a marker of the lipid profile
Effect of the RYGB on body weight 12 months Changes in the body weight (kg) of patients 12 months after the RYGB intervention determined with an electronic scale
Effect of the RYGB on Body Mass Index (BMI) 12 months Changes in the BMI (kg/m\^2) of patients 12 months after the RYGB intervention, measure by the formula: weight (kg) / \[height (m)\]\^2
Effect of the RYGB on Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) Index 12 months Changes in HOMA-IR Index of patients 12 months after the RYGB intervention, measured with the formula: \[Fasting Glucose (mg/dL) x Fasting Insulin (μU/mL)\]/405, as a marker of glucose metabolism
Effect of the RYGB on High Density Lipoprotein Cholesterol (HDLc) levels 12 months Changes in HDLc (mg/dL) of patients 12 months after the RYGB intervention, as a marker of the lipid profile
Effect of the RYGB on Low Density Lipoprotein Cholesterol (LDLc) levels 12 months Changes in LDLc (mg/dL) of patients 12 months after the RYGB intervention, as a marker of the lipid profile
Effect of the RYGB on high sensitivity C-Reactive Protein (hsCRP) levels 12 months Changes in hsCRP (mg/L) of patients 12 months after the RYGB intervention, as a marker of systemic inflammation
Remission rate for pathologies related to metabolic syndrome 12 months after RYGB intervention 12 months Percentage of cases of remission for hypertension, hyperlipidemia and type 2 diabetes (T2D) after the intervention.
Effect of the RYGB on fasting Insulin levels 12 months Changes in fasting Insulin (μU/mL) of patients 12 months after the RYGB intervention, as a marker of glucose metabolism
Changes in superoxide production 12 months after the RYGB intervention. 12 months Evaluation of superoxide production in leukocytes by means of fluorescence dye (Relative Fluorescence Units) as contributor to pro-oxidant processes.
Effect of the RYGB on fasting Glucose levels 12 months Changes in fasting Glucose (mg/dL) of patients 12 months after the RYGB intervention, as a marker of glucose metabolism
Effect of the RYGB on glycated hemoglobin (HbA1c) 12 months Changes in HbA1c (%) of patients 12 months after the RYGB intervention, as a marker of glucose metabolism
Changes in the protein expression of markers of nutrient sensing and ER stress in leukocytes 12 months after the RYGB intervention. 12 months Relative expression of proteins related to nutritional status, metabolism and Endoplasmic Reticulum (ER) stress (AMPK, SIRT1, ATF6, CHOP) assessed by western blot and normalized to the loading control protein.
Changes in serum MPO levels 12 months after the RYGB intervention. 12 months Evaluation of serum levels of the prooxidant MPO by immunoassay ELISA (ng/mL) as contributor to pro-oxidant and pro-inflammatory processes.
Changes in serum SOD enzymatic activity 12 months after the RYGB intervention. 12 months Evaluation of SOD enzymatic activity in serum (nmol/min/mL) as part of the systemic antioxidant defense system.
Changes in serum catalase enzymatic activity 12 months after the RYGB intervention. 12 months Evaluation of catalase enzymatic activity in serum (nmol/min/mL) as part of the systemic antioxidant defense system.
Effect of the RYGB on Total Cholesterol (TC) 12 months Changes in TC (mg/dL) of patients 12 months after the RYGB intervention, as a marker of the lipid profile
Effect of the RYGB on Interleukin-6 (IL6) levels 12 months Changes in IL6 (pg/mL) of patients 12 months after the RYGB intervention, as a marker of systemic inflammation
Effect of the RYGB on Interleukin-1 β (IL1β) levels 12 months Changes in IL1β (pg/mL) of patients 12 months after the RYGB intervention, as a marker of systemic inflammation
Trial Locations
- Locations (1)
Hospital Universitario Doctor Peset
🇪🇸Valencia, Spain