Long-Term High-Fat Diet Decreases Renal Insulin-Degrading Enzyme Expression and Function by Inhibiting the PPAR gamma Pathway

作者全名："Su, Qian; Huang, Juan; Chen, Xi; Wang, Yijie; Shao, Muqing; Yan, Hongjia; Chen, Caiyu; Ren, Hongmei; Zhang, Fuwei; Ni, Yinxing; Jose, Pedro A.; Zhong, Jian; Yang, Jian"

作者地址："[Su, Qian; Wang, Yijie; Shao, Muqing; Ni, Yinxing; Zhong, Jian] Chongqing Med Univ, Dept Endocrinol, Affiliated Hosp 3, Chongqing 401120, Peoples R China; [Su, Qian; Huang, Juan; Chen, Xi; Wang, Yijie; Shao, Muqing; Yan, Hongjia; Zhang, Fuwei; Ni, Yinxing; Zhong, Jian; Yang, Jian] Chongqing Med Univ, Res Ctr Metab & Cardiovasc Dis, Affiliated Hosp 3, Chongqing 401120, Peoples R China; [Huang, Juan; Chen, Xi; Yan, Hongjia; Yang, Jian] Chongqing Med Univ, Dept Clin Nutr, Affiliated Hosp 3, Chongqing 401120, Peoples R China; [Chen, Caiyu; Ren, Hongmei] Third Mil Med Univ, Daping Hosp, Dept Cardiol, Chongqing 400042, Peoples R China; [Zhang, Fuwei] Chongqing Med Univ, Dept Cardiol, Affiliated Hosp 3, Chongqing 401120, Peoples R China; [Jose, Pedro A.] George Washington Univ, Dept Med, Div Renal Dis & Hypertens, Sch Med & Hlth Sci, Washington, DC 20052 USA; [Jose, Pedro A.] George Washington Univ, Dept Physiol & Pharmacol, Sch Med & Hlth Sci, Washington, DC 20052 USA"

通信作者："Zhong, J (通讯作者)，Chongqing Med Univ, Dept Endocrinol, Affiliated Hosp 3, Chongqing 401120, Peoples R China.; Zhong, J; Yang, J (通讯作者)，Chongqing Med Univ, Res Ctr Metab & Cardiovasc Dis, Affiliated Hosp 3, Chongqing 401120, Peoples R China."

来源：MOLECULAR NUTRITION & FOOD RESEARCH

ESI学科分类：AGRICULTURAL SCIENCES

WOS号：WOS:000936026100001

JCR分区：Q1

影响因子：5.2

年份：2023

卷号：67

期号：7

开始页：　

结束页：　

文献类型：Article

关键词：high-fat diet; insulin clearance; insulin resistance; insulin-degrading enzyme; kidney

摘要："ScopeLong-term high-fat diet (HFD) causes insulin resistance, which is a primary etiological factor in the development of obesity and type 2 diabetes mellitus. Impaired insulin clearance is not only a consequence but also a cause of insulin resistance. The kidney is a major site of insulin clearance, where the insulin-degrading enzyme (IDE) plays a vital role in the proximal tubule. Thus, the study investigates the role of renal IDE in the regulation of insulin resistance in HFD-induced obese mice. Methods and resultsTwenty four-weeks of HFD in C57BL/6 mice causes insulin resistance and impaires insulin clearance, accompanied by a decrease in renal IDE expression and activity. Palmitic acid decreases IDE mRNA and protein expressions in HK-2 cells. RNA-Seq analysis found that the PPAR pathway is involved. 24-weeks of HFD decreases renal PPAR gamma, but not PPAR alpha or PPAR beta/delta mRNA expression. The inhibition of IDE expression by palmitic acid is prevented by the PPAR gamma agonist rosiglitazone. The amount of PPAR gamma bound to the promoters of IDE is decreased in palmitic acid-treated cells. Rosiglitazone improves insulin clearance and insulin resistance and increases renal IDE expression in HFD fed-mice. ConclusionLong-term HFD decreases renal IDE expression and activity, and causes insulin resistance, which involves PPAR gamma."

基金机构："National Natural Science Foundation of China [82070442, 81770425]; Scientific Research Project of Chongqing Education Commission [KJQN202200433]; Program of Chongqing Medical University for Youth Innovation in Future Medicine [W0085]; National Institutes of Health [P01HL074940, DK039308, DK119652]"

基金资助正文："This work was supported in part by grants from the National Natural Science Foundation of China (82070442, 81770425), Scientific Research Project of Chongqing Education Commission (KJQN202200433), Program of Chongqing Medical University for Youth Innovation in Future Medicine (W0085), and the National Institutes of Health (P01HL074940, DK039308, and DK119652)."