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

NCT05071391 | Completed

• 1 other identifier: PI16/00301
• Study Type: observational
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Obesity

Keywords

bariatric surgery; autophagy; inflammasome; atherosclerosis; cardiovascular disease

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  12 months

Secondary Outcomes (22)

• Changes in the protein expression of markers of mitochondrial dynamics and function in leukocytes 12 months after the RYGB intervention.

  12 months

• Changes in the protein expression of markers of nutrient sensing and ER stress in leukocytes 12 months after the RYGB intervention.

  12 months

• Changes in superoxide production 12 months after the RYGB intervention.

  12 months

• Changes in serum MPO levels 12 months after the RYGB intervention.

  12 months

• Changes in protein carbonylation in serum 12 months after the RYGB intervention.

  12 months

Study Arms (1)

Obese

Obese patients undergoing Roux-en-Y gastric bypass

Procedure: Roux-en-Y gastric bypass

Interventions

Roux-en-Y gastric bypass PROCEDURE

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.

Also known as: RYGB

Obese

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Subjects with obesity prescribed bariatric surgery to treat their obesity and related comorbidities

You may qualify if:

• Body Mass Index (BMI) ≥ 30 kg/m\^2
• duration of obesity over 5 years

You may not qualify if:

• 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)

Sponsors & Collaborators

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

Study Sites (1)

Hospital Universitario Doctor Peset

Valencia, 46017, Spain

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood

MeSH Terms

Conditions

Obesity; Atherosclerosis; Cardiovascular Diseases

Interventions

Gastric Bypass

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Bariatric Surgery; Bariatrics; Obesity Management; Therapeutics; Gastroenterostomy; Anastomosis, Surgical; Surgical Procedures, Operative; Digestive System Surgical Procedures

Study Officials

• Milagros Rocha Barajas, PhD

  Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Senior Researcher

Study Record Dates

• First Submitted: September 16, 2021
• First Posted: October 8, 2021
• Study Start: January 1, 2017
• Primary Completion: December 31, 2019
• Study Completion: December 31, 2019
• Last Updated: October 8, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)