Autophagy and Inflammasome in Obesity: Effect of Weight Loss and Potential Therapeutic Implications

Sponsor
Milagros Rocha Barajas (Other)
Overall Status
Completed
CT.gov ID
NCT05071391
Collaborator
Instituto de Salud Carlos III (Other), Hospital Universitario Doctor Peset (Other)
45
Enrollment
1
Location
35.9
Actual Duration (Months)
1.3
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or DiseaseIntervention/TreatmentPhase
  • Procedure: Roux-en-Y gastric bypass

Study Design

Study Type:
Observational
Actual Enrollment :
45 participants
Observational Model:
Cohort
Time Perspective:
Prospective
Official Title:
Role of Autophagy and Inflammasome in the Pathophysiology of Obesity: Effect of Weight Loss and Potential Therapeutic Implications
Actual Study Start Date :
Jan 1, 2017
Actual Primary Completion Date :
Dec 31, 2019
Actual Study Completion Date :
Dec 31, 2019

Arms and Interventions

ArmIntervention/Treatment
Obese

Obese patients undergoing Roux-en-Y gastric bypass

Procedure: Roux-en-Y gastric bypass
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.
Other Names:
  • RYGB
  • Outcome Measures

    Primary Outcome Measures

    1. 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.

    2. 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

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    5. 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.

    6. 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.

    7. 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.

    8. 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

    9. 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

    10. Effect of the RYGB on blood pressure [12 months]

      Changes in Systolic/Diastolic Blood Pressure levels (SBP/DBP) (mmHg) measured with a sphygmomanometer

    11. 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

    12. 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

    13. 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

    14. 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

    15. 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

    16. 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

    17. 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

    18. 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

    19. 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

    20. 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

    21. 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

    22. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Body Mass Index (BMI) ≥ 30 kg/m^2

    • duration of obesity over 5 years

    Exclusion Criteria:
    • 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)

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Hospital Universitario Doctor PesetValenciaSpain46017

    Sponsors and Collaborators

    • Milagros Rocha Barajas
    • Instituto de Salud Carlos III
    • Hospital Universitario Doctor Peset

    Investigators

    • Principal Investigator: Milagros Rocha Barajas, PhD, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Milagros Rocha Barajas, Senior Researcher, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
    ClinicalTrials.gov Identifier:
    NCT05071391
    Other Study ID Numbers:
    • PI16/00301
    First Posted:
    Oct 8, 2021
    Last Update Posted:
    Oct 8, 2021
    Last Verified:
    Sep 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Milagros Rocha Barajas, Senior Researcher, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 8, 2021