高脂饮食诱导肥胖易感和肥胖抵抗的表型差异

超重与肥胖是许多代谢相关疾病的危险因素，严重威胁人类健康和生命。通常认为肥胖的发生是遗传因素与环境因素相互作用的结果。在构建饮食性肥胖模型过程中，动物常出现两种截然不同的表型，即肥胖易感和肥胖抵抗。既往研究主要基于体重、体成分、物质与能量代谢、行为学（如摄食偏好）等探讨肥胖易感型和肥胖抵抗型表型差异，然而其内部调控机制，仍没有较为明确而系统的阐述。本文在综述表型特征的基础上，从脂质代谢、胃肠道激素水平和肠道炎症、肠道微生物群和肠-脑轴信号通路、下丘脑-垂体-甲状腺轴、下丘脑弓状核食欲调节系统功能改变以及表观遗传学等方面探讨高脂饮食诱导肥胖表型差异的可能机制。

The Phenotypic Differences in High-fat Diet-induced Obesity and Resistance

Overweight and obesity are risks for many metabolic diseases, posing a serious threat to human health and life. It is now clear that obesity is the result of genome-environment interaction. Obesity is a highly heritable and genetically heterogeneous disorder in humans and rodents. The high-fat diet is an important contributor to weight gain and the development of obesity. Previous studies found that high-fat diet can induce two completely distinct phenotypes in rodents, named diet-induced obesity (DIO) and diet-induced resistance (DR), which has different characteristics in weight, body composition, energy metabolism, feeding preference, etc. However, its internal mechanism is not fully known. Several studies suggested that lipid metabolism in liver, adipose tissue, intestinal tract, and skeletal muscle may contribute to the difference between DIO and DR. Additionally, the changes of gastrointestinal hormone secretion and intestinal inflammation would cause these two phenotypes. Moreover, there was a significant reduction in gut microbiota richness and diversity in DIO mice but not in DR mice, which may play an important role in the development of the obese phenotype. The gut-brain axis made the contributions to the control of food intake and obesity. And the hypothalamic-pituitary-thyroid (HPT) axis function and deiodinases activity might be involved in different propensities to obesity. Difference of NPY/AGRP, POMC/CART and their receptor gene expressions in hypothalamic arcuate nucleus was also the basis of the difference between the two phenotypes. But all these changes of physiology are strongly related to genetic mutations and genotype.