Mechanical regulation of lipid and sugar absorption by Piezo1 in enterocytes  

作　　者：Tian Tao Qing Shu Yawen Zhao Wenying Guo Jinting Wang Yuhao Shi Shiqi Jia Hening Zhai Hui Chen Cunchuan Wang Geyang Xu 

机构地区：[1]Department of Physiology,School of Medicine,Jinan University,Guangzhou 510632,China [2]Department of Metabolic and Bariatric Surgery,the First Affiliated Hospital of Jinan University,Guangzhou 510630,China [3]Endoscopy Center,the First Affiliated Hospital of Jinan University,Guangzhou 510630,China [4]Biotherapy Center,Cell-gene Therapy Translational Medicine Research Center,the Third Affiliated Hospital,Sun Yat-sen University,Guangzhou 510630,China [5]Key Laboratory of Viral Pathogenesis&Infection Prevention and Control(Jinan University),Ministry of Education,Guangzhou 510632,China

出　　处：《Acta Pharmaceutica Sinica B》2024年第8期3576-3590,共15页药学学报（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China(82170818,81770794);Guangdong Basic and Applied Basic Research Foundation(2024A1515010686,China);the Fundamental Research Funds for the Central Universities(21620423,China).

摘　　要：Obesity is primarily caused by excessive intake as well as absorption of sugar and lipid.Postprandial surge in distention pressure and intestinal motility accelerates the absorption of nutrients.The response of intestinal epithelial cells to mechanical stimulation is not fully understood.Piezo1,a mechanosensitive ion channel,is widely expressed throughout the digestive tract.However,its function in intestinal nutrient absorption is not yet clear.In our study,excessive lipid deposition was observed in the duodenum of obese patients,while duodenal Piezo1-CaMKK2-AMPKa was decreased when compared to normal-weight individuals.Under high-fat diet condition,the Piezo1iKO mice exhibited abnormally elevated sugar and lipid absorption as well as severe lipid deposition in the duodenum and liver.These phenotypes were mainly caused by the inhibition of duodenal CaMKK2-AMPKa and the upregulation of SGLT1 and DGAT2.In contrast,Yoda1,a Piezo1 agonist,was found to reduce intestinal lipid absorption in diet induced obese mice.Overexpression of Piezo1,stretch and Yoda1 inhibited lipid accumulation and the expression of DGAT2 and SGLT1,whereas knockdown of Piezo1 stimulated lipid accumulation and DGAT2 in Caco-2 cells.Our study reveals a previously unexplored mechanical regulation of nutrient absorption in intestinal epithelial cells,which may shed new light on the therapy of obesity.

关 键 词：Piezo1 DGAT2 SGLT1 Lipid metabolism OBESITY Mechanical sensing Intestinal lipid absorption Intestinal glucose absorption 

分 类 号：R392-33[医药卫生—免疫学]