Role of Autophagy and Inflammasome in the Pathophysiology of Obesity: Effect of Weight Loss and Potential Therapeutic Implications
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Changes in the protein expression of autophagy markers in leukocytes 12 months after the RYGB intervention
研究概览
简要总结
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Body Mass Index (BMI) ≥ 30 kg/m^2
- •duration of obesity over 5 years
排除标准
- •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)
结局指标
主要结局
Changes in the protein expression of autophagy markers in leukocytes 12 months after the RYGB intervention
时间窗: 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
时间窗: 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.
次要结局
- Changes in the protein expression of markers of mitochondrial dynamics and function in leukocytes 12 months after the RYGB intervention.(12 months)
- Changes in protein carbonylation in serum 12 months after the RYGB intervention.(12 months)
- Effect of the RYGB on blood pressure(12 months)
- Effect of the RYGB on Triglyceride (TG) levels(12 months)
- Effect of the RYGB on body weight(12 months)
- Effect of the RYGB on Body Mass Index (BMI)(12 months)
- Effect of the RYGB on Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) Index(12 months)
- Effect of the RYGB on High Density Lipoprotein Cholesterol (HDLc) levels(12 months)
- Effect of the RYGB on Low Density Lipoprotein Cholesterol (LDLc) levels(12 months)
- Effect of the RYGB on high sensitivity C-Reactive Protein (hsCRP) levels(12 months)
- Remission rate for pathologies related to metabolic syndrome 12 months after RYGB intervention(12 months)
- Effect of the RYGB on fasting Insulin levels(12 months)
- Changes in superoxide production 12 months after the RYGB intervention.(12 months)
- Effect of the RYGB on fasting Glucose levels(12 months)
- Effect of the RYGB on glycated hemoglobin (HbA1c)(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 serum MPO levels 12 months after the RYGB intervention.(12 months)
- Changes in serum SOD enzymatic activity 12 months after the RYGB intervention.(12 months)
- Changes in serum catalase enzymatic activity 12 months after the RYGB intervention.(12 months)
- Effect of the RYGB on Total Cholesterol (TC)(12 months)
- Effect of the RYGB on Interleukin-6 (IL6) levels(12 months)
- Effect of the RYGB on Interleukin-1 β (IL1β) levels(12 months)
研究者
Milagros Rocha Barajas
Senior Researcher
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana