Body Composition, Adiposity Phenotype, Metabolic Flexibility, and Gut Microbiota in PNPLA3 and TM6SF2 Gene Variant Carriers and Non-carriers With Nonalcoholic Fatty Liver Disease. Effects of a Nutritional Intervention Combined to Exercise
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 120
- 试验地点
- 2
- 主要终点
- Waist circumference measurements;
研究概览
简要总结
Nonalcoholic fatty liver disease (NAFLD) is associated to obesity, metabolic syndrome and genetic predisposition: specific variants of the genes PNPLA3 and TM6SF2 are the most involved. Also biochemical mechanisms that affect the "metabolic flexibility" need to be better clarified.
It is known that a dietary intervention, accompanied by a physical personalized training, reduce either the hepatic fat content either insulin resistance.
Therefore, the aim of the study is to evaluate "metabolic flexibility" in obese NAFLD subjects taking in account the presence or absence of PNPLA3 and TM6SF2 polymorphism and the histopathological diagnosis of either simple steatosis or nonalcoholic steatohepatitis (NASH). The composition of gut microbiota will be also evaluated.
Finally, two distinct healthy dietary profiles accompanied by a personalized physical training, will be tested to comprehend whether and how "healthy diets" could operate in the clinical treatment of NAFLD and related conditions.
详细描述
Nonalcoholic fatty liver disease (NAFLD) is frequently associated to obesity and metabolic syndrome. In NAFLD, a heritable component to disease susceptibility has been demonstrated: the variants of the genes PNPLA3 and TM6SF2 are the most involved genetic determinants.
To date, biochemical mechanisms that affect the "metabolic flexibility" in obese NAFLD subjects, in presence or absence of genetic susceptibility, need to be better clarified.
Different studies demonstrated that a dietary intervention, accompanied by a physical personalized training, significantly reduce either the hepatic fat content either insulin resistance in overweight and obese subjects, independently of weight loss.
On these bases, the aim of the study is to evaluate "metabolic flexibility" in obese NAFLD subjects taking in account their genetics (presence or absence of PNPLA3 and TM6SF2 polymorphisms) and the histopathological diagnosis of either simple steatosis or nonalcoholic steatohepatitis (NASH). In addition, the composition of gut microbiota will be evaluated.
Finally, in this study, two distinct healthy dietary profiles accompanied by a personalized physical training, will be tested in order to comprehend whether and how "healthy diets" could be effective not only in the prevention, but also in the clinical treatment of NAFLD and other related conditions.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
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
- 是
入选标准
- •body mass index (BMI) > 30 Kg/m2 and < 40 Kg/m2;
- •Caucasian Italian subjects
- •hepatic steatosis according with ultrasonographic Hamaguchi's criteria and/or hypertransaminasemia (ALT >30 IU/L in men and >20 IU/L in women)
排除标准
- •any malignant disease during the last 5 years;
- •any inflammatory or autoimmune disease;
- •corticosteroids for systemic use;
- •renal failure (GFR<90 ml/min);
- •heart failure (NYHA classes II-IV);
- •history of viral or autoimmune liver disease;
- •any cause cirrhosis;
- •excessive alcohol intake (>140g/week for men and 70g/week for women);
- •participation in a reducing-weight program in the last 3 months;
- •level of physical activity higher than 3 METs;
- •therapy with antibiotics during the last 3 months;
- •bile salts, cholestyramine during the last 6 months before enrollment;
- •previous cholecystectomy;
- •gallbladder disease
结局指标
主要结局
Waist circumference measurements;
时间窗: 18 weeks after baseline
waist circumference reported as cm
Insulinemia
时间窗: 18 weeks after baseline
insulin reported as µU/mL
triglycerides assessment
时间窗: 18 weeks after baseline
tryglicerides levels reported as mg/dl
Glucidic profile
时间窗: 18 weeks after baseline
fasting glucose reported as mg/dl
Cholesterol assessment
时间窗: 18 weeks after baseline
total cholesterol, HDL- cholesterol, LDL- cholesterol levels reported as mg/dl
metabolic flexibility variation in liver function;
时间窗: 18 weeks after baseline
alanine aminotransferase (ALT) \[U/L\] , aspartate aminotransferase (AST) \[UI/L\]
anthropometric measurements;
时间窗: 18 weeks after baseline
Body mass index reported as kg/m\^2
Ultrasonographic examination;
时间窗: 18 weeks after baseline
Liver ultrasonography according with criteria by Hamaguchi
次要结局
未报告次要终点
研究者
STEFANO GINANNI CORRADINI
Associate Professor
University of Roma La Sapienza