Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Duke Molecular Physiology Institute, Duke University, Durham, NC 27701, USA.
Nutrients. 2021 Oct 18;13(10):3642. doi: 10.3390/nu13103642.
The metabolic syndrome (MetS), defined as the co-occurrence of disorders including obesity, dyslipidemia, insulin resistance, and hepatic steatosis, has become increasingly prevalent in the world over recent decades. Dietary and other environmental factors interacting with genetic predisposition are likely contributors to this epidemic. Among the involved dietary factors, excessive fructose consumption may be a key contributor. When fructose is consumed in large amounts, it can quickly produce many of the features of MetS both in humans and mice. The mechanisms by which fructose contributes to metabolic disease and its potential interactions with genetic factors in these processes remain uncertain. Here, we generated a small F2 genetic cohort of male mice derived from crossing fructose-sensitive and -resistant mouse strains to investigate the interrelationships between fructose-induced metabolic phenotypes and to identify hepatic transcriptional pathways that associate with these phenotypes. Our analysis indicates that the hepatic transcriptional pathways associated with fructose-induced hypertriglyceridemia and hyperinsulinemia are distinct from those that associate with fructose-mediated changes in body weight and liver triglyceride. These results suggest that multiple independent mechanisms and pathways may contribute to different aspects of fructose-induced metabolic disease.
代谢综合征（MetS）是指肥胖、血脂异常、胰岛素抵抗和肝脂肪变性等多种疾病同时发生，近年来在全球范围内越来越普遍。饮食和其他环境因素与遗传易感性相互作用，可能是导致这种流行的原因。在涉及的饮食因素中，过量摄入果糖可能是一个关键因素。当大量摄入果糖时，它会在人类和小鼠中迅速产生许多代谢综合征的特征。果糖导致代谢疾病的机制及其在这些过程中与遗传因素的潜在相互作用仍不确定。在这里，我们生成了一个由雄性小鼠组成的小型 F2 遗传队列，这些小鼠是通过交叉果糖敏感和耐受的小鼠品系产生的，以研究果糖诱导的代谢表型之间的相互关系，并鉴定与这些表型相关的肝转录途径。我们的分析表明，与果糖诱导的高甘油三酯血症和高胰岛素血症相关的肝转录途径与与果糖介导的体重和肝甘油三酯变化相关的途径不同。这些结果表明，多种独立的机制和途径可能导致果糖诱导的代谢疾病的不同方面。
