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.
Study Type
OBSERVATIONAL
Enrollment
45
Gastric bypass, also called Roux-en-Y gastric bypass, is a type of weight-loss surgery that involves creating a small pouch from the stomach and connecting the newly created pouch directly to the small intestine. After gastric bypass, swallowed food will go into this small pouch of stomach and then directly into the small intestine, thereby bypassing most of your stomach and the first section of your small intestine. Gastric bypass is one of the most commonly performed types of bariatric surgery. Gastric bypass is done when diet and exercise haven't worked or when you have serious health problems because of your weight.
Hospital Universitario Doctor Peset
Valencia, Spain
Changes in the protein expression of autophagy markers in leukocytes 12 months after the RYGB intervention
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.
Time frame: 12 months
Changes in the relative protein expression of inflammatory mediators in leukocytes 12 months after the RYGB intervention
Relative expression of intracellular proteins related to inflammatory pathways (MCP1, NF-kB) assessed by western blot and normalized to the loading control protein.
Time frame: 12 months
Changes in the protein expression of markers of mitochondrial dynamics and function in leukocytes 12 months after the RYGB intervention.
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.
Time frame: 12 months
Changes in the protein expression of markers of nutrient sensing and ER stress in leukocytes 12 months after the RYGB intervention.
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.
Time frame: 12 months
Changes in superoxide production 12 months after the RYGB intervention.
Evaluation of superoxide production in leukocytes by means of fluorescence dye (Relative Fluorescence Units) as contributor to pro-oxidant processes.
Time frame: 12 months
Changes in serum MPO levels 12 months after the RYGB intervention.
Evaluation of serum levels of the prooxidant MPO by immunoassay ELISA (ng/mL) as contributor to pro-oxidant and pro-inflammatory processes.
Time frame: 12 months
Changes in protein carbonylation in serum 12 months after the RYGB intervention.
Evaluation of carbonyl groups in serum proteins by means of immunoassay ELISA (nmol/mg protein) as a marker of systemic oxidative damage.
Time frame: 12 months
Changes in serum SOD enzymatic activity 12 months after the RYGB intervention.
Evaluation of SOD enzymatic activity in serum (nmol/min/mL) as part of the systemic antioxidant defense system.
Time frame: 12 months
Changes in serum catalase enzymatic activity 12 months after the RYGB intervention.
Evaluation of catalase enzymatic activity in serum (nmol/min/mL) as part of the systemic antioxidant defense system.
Time frame: 12 months
Effect of the RYGB on body weight
Changes in the body weight (kg) of patients 12 months after the RYGB intervention determined with an electronic scale
Time frame: 12 months
Effect of the RYGB on Body Mass Index (BMI)
Changes in the BMI (kg/m\^2) of patients 12 months after the RYGB intervention, measure by the formula: weight (kg) / \[height (m)\]\^2
Time frame: 12 months
Effect of the RYGB on blood pressure
Changes in Systolic/Diastolic Blood Pressure levels (SBP/DBP) (mmHg) measured with a sphygmomanometer
Time frame: 12 months
Effect of the RYGB on fasting Glucose levels
Changes in fasting Glucose (mg/dL) of patients 12 months after the RYGB intervention, as a marker of glucose metabolism
Time frame: 12 months
Effect of the RYGB on fasting Insulin levels
Changes in fasting Insulin (μU/mL) of patients 12 months after the RYGB intervention, as a marker of glucose metabolism
Time frame: 12 months
Effect of the RYGB on Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) Index
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
Time frame: 12 months
Effect of the RYGB on glycated hemoglobin (HbA1c)
Changes in HbA1c (%) of patients 12 months after the RYGB intervention, as a marker of glucose metabolism
Time frame: 12 months
Effect of the RYGB on Total Cholesterol (TC)
Changes in TC (mg/dL) of patients 12 months after the RYGB intervention, as a marker of the lipid profile
Time frame: 12 months
Effect of the RYGB on High Density Lipoprotein Cholesterol (HDLc) levels
Changes in HDLc (mg/dL) of patients 12 months after the RYGB intervention, as a marker of the lipid profile
Time frame: 12 months
Effect of the RYGB on Low Density Lipoprotein Cholesterol (LDLc) levels
Changes in LDLc (mg/dL) of patients 12 months after the RYGB intervention, as a marker of the lipid profile
Time frame: 12 months
Effect of the RYGB on Triglyceride (TG) levels
Changes in TG (mg/dL) of patients 12 months after the RYGB intervention, as a marker of the lipid profile
Time frame: 12 months
Effect of the RYGB on high sensitivity C-Reactive Protein (hsCRP) levels
Changes in hsCRP (mg/L) of patients 12 months after the RYGB intervention, as a marker of systemic inflammation
Time frame: 12 months
Effect of the RYGB on Interleukin-6 (IL6) levels
Changes in IL6 (pg/mL) of patients 12 months after the RYGB intervention, as a marker of systemic inflammation
Time frame: 12 months
Effect of the RYGB on Interleukin-1 β (IL1β) levels
Changes in IL1β (pg/mL) of patients 12 months after the RYGB intervention, as a marker of systemic inflammation
Time frame: 12 months
Remission rate for pathologies related to metabolic syndrome 12 months after RYGB intervention
Percentage of cases of remission for hypertension, hyperlipidemia and type 2 diabetes (T2D) after the intervention.
Time frame: 12 months
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