JRG Adipocytes and Metabolism, Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Center Munich, Garching, Germany.
German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
Int J Obes (Lond). 2018 Mar;42(3):507-517. doi: 10.1038/ijo.2017.224. Epub 2017 Sep 13.
BACKGROUND/OBJECTIVES: Dieting is a popular yet often ineffective way to lower body weight, as the majority of people regain most of their pre-dieting weights in a relatively short time. The underlying molecular mechanisms driving weight regain and the increased risk for metabolic disease are still incompletely understood. Here we investigate the molecular alterations inherited from a history of obesity.
In our model, male high-fat diet (HFD)-fed obese C57BL/6J mice were switched to a low caloric chow diet, resulting in a decline of body weight to that of lean mice. We measured body composition, as well as metrics of glucose, insulin and lipid homeostasis. This was accompanied by histological and gene expression analysis of adipose tissue and liver to assess adipose tissue inflammation and hepatosteatosis. Moreover, acute hypothalamic response to (re-) exposure to HFD was assessed by qPCR.
RESULTS & CONCLUSIONS: Within 7 weeks after diet switch, most obesity-associated phenotypes, such as body mass, glucose intolerance and blood metabolite levels were reversed. However, hepatic inflammation, hepatic steatosis as well as hypertrophy and inflammation of perigonadal, but not subcutaneous, adipocytes persisted in formerly obese mice. Transcriptional profiling of liver and perigonadal fat revealed an upregulation of pathways associated with immune function and cellularity. Thus, we show that weight reduction leaves signs of inflammation in liver and perigonadal fat, indicating that persisting proinflammatory signals in liver and adipose tissue could contribute to an increased risk of formerly obese subjects to develop the metabolic syndrome upon recurring weight gain.
背景/目的：节食是一种常见但通常无效的降低体重的方法，因为大多数人会在相对较短的时间内恢复大部分节食前的体重。导致体重反弹和代谢性疾病风险增加的潜在分子机制仍不完全清楚。在这里，我们研究了从肥胖史中遗传下来的分子变化。
在我们的模型中，雄性高脂肪饮食（HFD）喂养的肥胖 C57BL/6J 小鼠被切换到低热量的饲料饮食，导致体重下降到瘦鼠的水平。我们测量了身体成分，以及葡萄糖、胰岛素和脂质稳态的指标。这伴随着脂肪组织和肝脏的组织学和基因表达分析，以评估脂肪组织炎症和肝脂肪变性。此外，通过 qPCR 评估急性下丘脑对（重新）暴露于 HFD 的反应。
在饮食转换后的 7 周内，大多数与肥胖相关的表型，如体重、葡萄糖耐量和血液代谢物水平都得到了逆转。然而，肝炎症、肝脂肪变性以及腹膜后脂肪的肥大和炎症，而不是皮下脂肪，在以前肥胖的小鼠中仍然存在。肝脏和腹膜后脂肪的转录谱分析显示，与免疫功能和细胞活力相关的途径上调。因此，我们表明，体重减轻会在肝脏和腹膜后脂肪中留下炎症的迹象，这表明肝脏和脂肪组织中持续存在的促炎信号可能会增加以前肥胖者在体重再次增加时患上代谢综合征的风险。
