Effect of Sleeve Gastrectomy on Glucose Metabolism and Autophagy in Obese Mice
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摘要:
目的 探讨肥胖体质小鼠在接受袖状胃切除术（sleeve sastrectomy，SG）前后肝脏自噬因子活性的变化。 方法 6～8周龄的雄性肥胖小鼠随机分成假手术组（Sham组，n=6）和袖状胃切除手术组（SG组，n=6），在术后1个月内记录2组小鼠每日体重和日摄食量，并在术后15 d和30 d时测定小鼠尾尖末端空腹血糖值，进行口服葡萄糖耐量试验以评估葡萄糖的吸收情况；采用RT-qPCR检测术后15 d和30 d自噬因子以及葡萄糖转运蛋白的mRNA表达变化情况。 结果 与术前相比，Sham组术后15 d和30 d的体重、日摄食量、空腹血糖值差异均无统计学意义（P > 0.05），而SG组术后15 d和30 d体重、日摄食量、空腹血糖值均降低且差异具有统计学意义（P < 0.05）；与Sham组相比，SG组15 d和30 d的体重、日摄食量、空腹血糖均减少，且差异具有统计学意义（P < 0.05），SG组小鼠自噬因子P62增高，而Beclin-1、LC3I/LC3II及SGLT1的mRNA表达在术后15 d和30 d均降低，且差异具有统计学意义（P < 0.05）。 结论 SG能够减少小鼠肠道葡萄糖吸收来降低血糖，通过改善脂质代谢来控制体重进而调节小鼠肝脏自噬活性。 Abstract:Objective To investigate the changes in liver autophagy factor activity in obese mice before and after sleeve gastrectomy（SG）. Methods Male obese mice aged 6-8 weeks were randomly divided into a sham surgery group (Sham group, n=6) and a sleeve gastrectomy surgery group （SG group, n=6）. The daily weight and food intake of the two groups of mice were recorded within one month after surgery, and the fasting blood glucose values at the tip of the mouse tail were measured at 15 and 30 days after surgery. Oral glucose tolerance tests were performed to evaluate glucose absorption; RT-qPCR was used to detect the mRNA expression changes of autophagy factors and glucose transporters at 15 and 30 days after surgery. Results Compared with preoperation, there was no statistically significant difference（P > 0.05） in the weight, daily food intake, and fasting blood glucose values of the sham surgery group at 15 and 30 days after surgery, while the SG group had a decrease in weight, daily food intake, and fasting blood glucose values at 15 and 30 days after surgery and had a statistically significant difference（P < 0.05）; Compared with the sham surgery group, the weight, daily food intake, and fasting blood glucose of the SG group decreased and showed statistical differences（P < 0.05） at 15 and 30 days. The autophagy factor P62 in the SG group mice increased, while the mRNA expression of Beclin-1, LC3I/LC3II, and SGLT1 decreased and showed statistical differences（P < 0.05） at 15 and 30 days after surgery. Conclusion SG can improve obesity and reduce inflammatory mediators and adipokines, further regulating autophagic activity in mouse liver. -
图 1 小鼠体重和日摄食量的变化（χ2±SEM，n=6）
A：Sham组与SG组术后30 d内小鼠体重的变化；B：Sham组与SG组术后30 d内小鼠日摄食量的变化。与Sham组比较，*P < 0.05，**0.05 < P < 0.01，***P < 0.001。
Figure 1. Changes in body mass and daily food intake of mice （χ2±SEM，n=6）
图 2 小鼠空腹血糖值、口服葡萄糖耐量试验血糖变化及曲线下面积（χ2±SEM，n=6）
A：Sham组与SG组术前、术后15 d和30 d小鼠的空腹血糖值；B~E：Sham组与SG组小鼠术后15 d、30 d进行口服葡萄糖耐量试验血糖变化水平及血糖变化曲线下面积。与Sham组比较，ns P > 0.05，*P < 0.05，**P < 0.01，***P < 0.001。
Figure 2. Fasting blood glucose levels，oral glucose tolerance test blood glucose changes，and area under the curve in mice （χ2±SEM，n=6）
图 3 术后肝脏自噬因子（P62、Beclin-1、LC3I、LC3II）及肠道SGLT1的mRNA表达变化（χ2±SEM，n=6）
A：Sham组与SG组术后15 d、30 d小肠的SGLT1 mRNA表达丰度；B：Sham组与SG组术后15 d、30 d肝脏的P62 mRNA表达丰度；C：Sham组与SG组术后15 d、30 d肝脏的Beclin-1 mRNA表达丰度；D~E：Sham组与SG组术后15 d、30 d肝脏的LC3I、LC3II mRNA表达丰度。与Sham组比较，ns P > 0.05，*P < 0.05，**P < 0.01，***P < 0.001。
Figure 3. Changes in mRNA expression of liver autophagy factors （P62，Beclin-1，LC3I，LC3II） and intestinal SGLT1 after surgery（χ2±SEM，n=6）
表 1 引物序列
Table 1. Primer sequence
基因 正向引物 反向引物 SGLT1 F：5'-CCAAGCCCATCCCAGACGTACACCC-3' R：5'-CTTCCTTAGTCATCTTCGGTCCTT-3' P62 F：5'-ATGTGGAACATGGAGGGAAGA-3' R：5'-GGAGTTCACCTGTAGATGGGT-3' Beclin1 F：5'-CCAGATGCGTTATGCCCAGAC-3' R：5'-CATTCCATTCCACGGGAACAC-3' LC3I F：5'-TATGGCACCAGTACGACG-3' R：5'-GCATTGTCAGTCACC-3' LC3II F：5'-TAGGCGATATAGCCGAACG-3' R：5'-CGGATAATGGATCAT-3' GAPDH F：5'-AGGTCGGTGTGAACGGATTTG-3' R：5'-TGTAGACCATGTAGTTGAGGTCA-3' 
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[1] Salah R O, Ghandour R, Husseini A. Prevalence of overweight, obesity, and associated factors among adolescents in the occupied Palestinian territory: A cross-sectional study[J]. Lancet, 2021, 398（Suppl 1）: S46. [2] Ruze R, Liu T, Zou X, et al. Obesity and type 2 diabetes mellitus: connections in epidemiology, pathogenesis, and treatments[J]. Front Endocrinol (Lausanne), 2023, Apr 21;14: 1161521. [3] Runkel N,Brydniak R. Surgical treatment of metabolic syndromeJ7[J]. Visc Med,2016,32(5):352-356. doi: 10.1159/000449110 [4] Aminian A,Wilson R,Zajichek A,et al. Cardiovascular outcomes in patients with type 2 diabetes and obesity: Comparison of gastric bypass,sleeve gastrectomy,and usual care[J]. Diabetes Care,2011,44(11):2552-2563. [5] Schauer P R, Bhatt D L, Kirwan J P, et al．Bariatric surgeryversus intensive medical therapy for diabetes-3-year out-comes[J]. The New England Journal of Medicine. 2015, 370(21):2002-2013. [6] Lippai M, Szatmari Z. Autophagy-from molecular mechanisms to clinical relevance[J]. Cell Biol Toxicol, 2017, 33（2）: 145-168 . [7] Debnath J, Gammoh N, Ryan KM. Autophagy and autophagy-related pathways in cancer[J]. Nat Rev Mol Cell Biol. 2023, 24(8):560-575. [8] Zhang Y, Higgins C B, Van Tine B A, et al. Pegylated arginine deiminase drives arginine turnover and systemic autophagy to dictate energy metabolism[J]. Cell Rep Med. 2022 Jan 18;3（1）: 100498. [9] Barzin M,Khalaj A,Motamedi M A,et al. Safety and effectiveness of sleeve gastrectomy versus gastric bypass: one-year results of Tehran Obesity Treatment Study (TOTS)[J]. Gastroenterol Hepatol Bed Bench,2016,9(Suppl1):S62-S69. [10] 程津津, 任萍萍. 学习《关于善待实验动物的指导性意见》后的体会[J].实验动物科学, 2011, 28（03）: 78-79. [11] Yardimci E,Bozkurt S,Cengiz M B,et al. Comparison of WeightLoss,Ghrelin,and LeptinHormones After Ligation of Left Gastric Artery and Sleeve Gastrectomy in a Rat Model[J]. Medicalscience Monitor,2017,Mar 24; 23:1442-1447. [12] Xia Jun, He Qian, He Ming, et al. Residual Gastric Dilatation Interferes with Metabolic Improvements Following Sleeve Gastrectomy by Upregulating the Expression of Sodium-Glucose Cotransporter-1[J]. Obesity Surgery, 2019, 29（10）: 3324-3333. [13] Evers S S, Lewis A G, Tong C, et al. The Unconventional Role for Gastric Volume in the Response to Bariatric Surgery for Both Weight Loss and Glucose Lowering[J]. Ann Surg, 2020, 271（6）: 1102-1109. [14] Santoleri D, Titchenell PM. Resolving the Paradox of Hepatic Insulin Resistance[J]. Cell Mol Gastroenterol Hepatol, 2019, 7（2）: 447-456. [15] Ye R, Gordillo R, Shao M, et al. Intracellular lipid metabolism impairs β cell compensation during diet-induced obesity[J]. J Clin Invest, 2018, 128（3）: 1178-1189. [16] Song H, Zhang X, Wang J, et al. The regulatory role of adipocyte mitochondrial homeostasis in metabolism-related diseases[J]. Front Physiol, 2023, Oct 18; 14: 1261204. [17] 徐春阳,李文兰,杨秀颖,等. 脂肪代谢障碍与抗炎治疗策略[J]. 中药药理与临床,2018,34(5):168-172. [18] Song B Q,Chi Y,Li X,et al. Inhibition of notch signaling promotes the adipogenic differentiation of mesenchymal stem cells through autophagy activation and PTEN-PI3K /AKT /mTOR pathway[J]. Cell Physiol Biochem,2015,36(5):1991-2002. doi: 10.1159/000430167 [19] Ma T,Li J,Xu Y,et al. Atg5-independent autophagy regulates mitochondrial clearance and is essential for iPSC reprogramming[J]. Nat Cell Biol,2015,17(11):1379-1387. doi: 10.1038/ncb3256 [20] Tao Z,Liu L,Zheng L D,et al. Autophagy in Adipocyte Differentiation[J]. Methods in Molecular Biology,2019,1854:45-53. [21] Matsuzawa-Ishimoto Y, Hwang S, Cadwell K. Autophagy and Inflammation [J]. Annu Rev Immunol. 2018 Apr 26, 36:73-101. [22] 张一文,喻松仁,姚琦,等. 细胞自噬调控肥胖脂肪组织炎症状态的研究进展[J]. 江西中医药,2020,51(8):77-80. [23] Weidberg H, Shvets E, ShpiLKAka T, et al. LC3 and GATE-16/GABARAP subfamilies are both essential yet act differently in autophagosome biogenesis [J/OL]. EMBO J, 2010, 29 （11）: 1792-1802 . [24] Wang K,Chen Y,Zhang P,et al. Protective features of autophagy in pulmonary infection and inflammatory diseases[J]. Cells,2019,8(2):123. doi: 10.3390/cells8020123 [25] Marasco M R,Linnemann A K. Beta-cell autophagy in diabetes pathogenesis[J]. Endocrinology,2018,159(5):2127. doi: 10.1210/en.2017-03273 [26] 杨丽娟,洪逸莲,林怡,等. 人参皂苷 Rb2 通过抑制自噬促进肥胖小鼠白色脂肪棕色化[J]. 中华内分泌代谢杂志,2020,36(12):1055-1061. [27] Barlow A D,Thomas D C. Autophagy in diabetes: beta cell dysfunction,insulin resistance,and complications[J]. DNA Cell Biol,2015,34(4):252-260. doi: 10.1089/dna.2014.2755 [28] Kim K H,Lee M S. Autophagy-a key player in cellular and body metabolism[J]. Nat Rev Endocrinol,2015,10(6):322-337. [29] Gonzalez C D,Lee M S,Marchetti P,et al. The emerging role of autophagy in the pathophysiology of diabetes mellitus[J]. Autophagy,2011,7(1):2-11. doi: 10.4161/auto.7.1.13044 [30] Kosacka J, Kern M, Klöting N, et al. Autophagy in adipose tissue of patients with obesity and type 2 diabetes [J]. Molecular and Cellular Endocrinology, 2015, 409（Issue C）: 21-32. [31] 李璇, 向小姣, 刘露路, 等. 自噬相关基因在肥胖患者及肥胖小鼠脂肪组织中的研究[J]. 重庆医科大学学报, 2016, 41（11）: 1159-1162. 期刊类型引用(6)
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