Li Peixin, Rao Zhijian, Laing Brenton Thomas, Bunner Wyatt, Landry Taylor, Prete Amber, Yuan Yuan, Zhang Zhong-Tao, Huang Hu
Department of Comprehensive Surgery, Medical and Health Center, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.
East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, North Carolina, USA.
J Endocrinol. 2019 May;241(2):135-147. doi: 10.1530/JOE-18-0658.
Vertical sleeve gastrectomy (VSG) is an effective surgery to treat obesity and diabetes. However, the direct effect of VSG on metabolic functions is not fully understood. We aimed to investigate if alterations in hypothalamic neurons were linked with perturbations in liver metabolism after VSG in an energy intake-controlled obese mouse model. C57BL/6 and hrNPY-GFP reporter mice received HFD for 12 weeks and were then divided into three groups: Sham (ad lib), Sham (pair-fed) with VSG and VSG. Food intake was measured daily, and blood glucose levels were measured before and after the study. Energy expenditure and body composition were determined. Serum parameters, liver lipid and glycogen contents were measured and gene/protein expression were analyzed. Hypothalamic POMC, AgRP/NPY and tyrosine hydroxylase-expressing neurons were counted. The following results were obtained. VSG reduced body weight gain and adiposity induced by HFD, increased energy expenditure independent of energy intake. Fed and fasted blood glucose levels were reduced in the VSG group. While serum active GLP-1 level was increased, the active ghrelin and triglycerides levels were decreased along with improved insulin resistance in VSG group. Liver lipid accumulation, glycogen content and gluconeogenic gene expression were reduced in the VSG group. In the hypothalamus, TH-expressing neuron population was decreased, and the POMC-expressing neuron population was increased in the VSG group. In conclusion, our data suggest that VSG improves metabolic symptoms by increasing energy expenditure and lowering lipid and glycogen contents in the liver. These physiological alterations are possibly related to changes in hypothalamic neuron populations.
垂直袖状胃切除术（VSG）是一种治疗肥胖症和糖尿病的有效手术。然而，VSG对代谢功能的直接影响尚未完全明确。我们旨在研究在能量摄入受控的肥胖小鼠模型中，VSG术后下丘脑神经元的改变是否与肝脏代谢紊乱有关。C57BL/6和hrNPY-GFP报告基因小鼠接受12周的高脂饮食，然后分为三组：假手术组（自由进食）、假手术组（配对喂食）伴VSG和VSG组。每天测量食物摄入量，并在研究前后测量血糖水平。测定能量消耗和身体组成。测量血清参数、肝脏脂质和糖原含量，并分析基因/蛋白质表达。对下丘脑表达POMC、AgRP/NPY和酪氨酸羟化酶的神经元进行计数。获得了以下结果。VSG减少了高脂饮食诱导的体重增加和肥胖，增加了与能量摄入无关的能量消耗。VSG组的进食和空腹血糖水平降低。VSG组血清活性GLP-1水平升高，活性胃饥饿素和甘油三酯水平降低，同时胰岛素抵抗得到改善。VSG组肝脏脂质积累、糖原含量和糖异生基因表达降低。在下丘脑中，VSG组表达TH的神经元数量减少，表达POMC的神经元数量增加。总之，我们的数据表明，VSG通过增加能量消耗和降低肝脏脂质及糖原含量来改善代谢症状。这些生理改变可能与下丘脑神经元数量的变化有关。
