Baldassano Sara, Amato Antonella, Rappa Francesca, Cappello Francesco, Mulè Flavia
a Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF) , Università di Palermo , Italy.
b Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche - Università di Palermo , Italy.
Endocr Res. 2016 Nov;41(4):317-324. doi: 10.3109/07435800.2016.1141950. Epub 2016 Feb 23.
The purpose of the present study was to investigate the influence of endogenous glucagon-like peptide-2 (GLP-2) on lipid profile in mice fed a standard diet (STD) or a high-fat diet (HFD).
HFD- and age-matched STD mice were injected once a day with GLP-2 (3-33), a GLP-2 receptor (GLP-2R) antagonist, or vehicle for 4 weeks.
HFD mice displayed increased intrahepatic lipid concentration and hepatic steatosis and higher plasma concentrations of cholesterol, LDL, AST, and ALT than STD mice. No difference was observed in lipid fecal elimination. In STD mice, the chronic treatment with GLP-2 (3-33) did not affect any parameter, while in HFD mice, it enhanced plasma triglycerides, cholesterol, ALT, and AST and reduced HDL, it increased intrahepatic lipid concentration, and it worsened the hepatic steatosis degree, without affecting lipid fecal elimination.
The present results suggest that GLP-2R antagonism worsens lipid disorders in HFD mice, and endogenous GLP-2 might even exert a defensive role against lipid imbalance.
本研究旨在探究内源性胰高血糖素样肽-2(GLP-2)对喂食标准饮食(STD)或高脂饮食(HFD)小鼠血脂谱的影响。
将高脂饮食和年龄匹配的标准饮食小鼠每天注射一次GLP-2(3-33)、GLP-2受体(GLP-2R)拮抗剂或赋形剂,持续4周。
与标准饮食小鼠相比,高脂饮食小鼠肝内脂质浓度升高、出现肝脂肪变性,血浆胆固醇、低密度脂蛋白、天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)浓度更高。粪便脂质排泄未观察到差异。在标准饮食小鼠中,用GLP-2(3-33)进行慢性治疗未影响任何参数,而在高脂饮食小鼠中,它提高了血浆甘油三酯、胆固醇、ALT和AST水平,降低了高密度脂蛋白(HDL)水平,增加了肝内脂质浓度,加重了肝脂肪变性程度,但不影响粪便脂质排泄。
目前的结果表明,GLP-2R拮抗作用会加重高脂饮食小鼠的脂质紊乱,内源性GLP-2甚至可能对脂质失衡发挥防御作用。