Ullah Amin, Singla Rajeev K, Batool Zahra, Cao Dan, Shen Bairong
Department of Abdominal Oncology, Cancer Center of West China Hospital and Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China.
School of Pharmaceutical Sciences, Lovely Professional University, 144411, Phagwara, Punjab, India.
Rev Endocr Metab Disord. 2024 Aug;25(4):783-803. doi: 10.1007/s11154-024-09884-y. Epub 2024 May 6.
Childhood obesity is a chronic inflammatory epidemic that affects children worldwide. Obesity affects approximately 1 in 5 children worldwide. Obesity in children can worsen weight gain and raise the risk of obesity-related comorbidities like diabetes and non-alcoholic fatty liver disease (NAFLD). It can also negatively impact the quality of life for these children. Obesity disrupts immune system function, influencing cytokine (interleukins) balance and expression levels, adipokines, and innate and adaptive immune cells. The altered expression of immune system mediators, including interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-17 (IL-17), interleukin-18 (IL-18), transforming growth factor (TGF), tumor necrosis factor (TNF), and others, caused inflammation, progression, and the development of pediatric obesity and linked illnesses such as diabetes and NAFLD. Furthermore, anti-inflammatory cytokines, including interleukin-2 (IL-2), have been shown to have anti-diabetes and IL-1 receptor antagonist (IL-1Ra) anti-diabetic and pro-NAFLFD properties, and interleukin-10 (IL-10) has been shown to have a dual role in managing diabetes and anti-NAFLD. In light of the substantial increase in childhood obesity-associated disorders such as diabetes and NAFLD and the absence of an effective pharmaceutical intervention to inhibit immune modulation factors, it is critical to consider the alteration of immune system components as a preventive and therapeutic approach. Thus, the current review focuses on the most recent information regarding the influence of pro- and anti-inflammatory cytokines (interleukins) and their molecular mechanisms on pediatric obesity-associated disorders (diabetes and NAFLD). Furthermore, we discussed the current therapeutic clinical trials in childhood obesity-associated diseases, diabetes, and NAFLD.
儿童肥胖是一种影响全球儿童的慢性炎症性流行病。全球约五分之一的儿童受肥胖影响。儿童肥胖会加剧体重增加，并增加患糖尿病和非酒精性脂肪性肝病（NAFLD）等肥胖相关合并症的风险。它还会对这些儿童的生活质量产生负面影响。肥胖会扰乱免疫系统功能，影响细胞因子（白细胞介素）平衡和表达水平、脂肪因子以及先天和适应性免疫细胞。免疫系统介质表达的改变，包括白细胞介素-1（IL-1）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、白细胞介素-17（IL-17）、白细胞介素-18（IL-18）、转化生长因子（TGF）、肿瘤坏死因子（TNF）等，导致了儿童肥胖及其相关疾病如糖尿病和NAFLD的炎症、进展和发展。此外，抗炎细胞因子，包括白细胞介素-2（IL-2），已被证明具有抗糖尿病作用，白细胞介素-1受体拮抗剂（IL-1Ra）具有抗糖尿病和促NAFLFD特性，白细胞介素-10（IL-10）在糖尿病管理和抗NAFLD方面具有双重作用。鉴于儿童肥胖相关疾病如糖尿病和NAFLD的大幅增加，以及缺乏抑制免疫调节因子的有效药物干预措施，将免疫系统成分的改变作为一种预防和治疗方法至关重要。因此，本综述重点关注促炎和抗炎细胞因子（白细胞介素）对儿童肥胖相关疾病（糖尿病和NAFLD）的影响及其分子机制的最新信息。此外，我们还讨论了目前针对儿童肥胖相关疾病、糖尿病和NAFLD的治疗性临床试验。
