PDF(Pubmed)
Abstract：
(1) Background: Proglucagon-derived peptides (PDGPs) including glucagon (Gcg), GLP-1, and GLP-2 regulate lipid metabolism in the liver, adipocytes, and intestine. However, the mechanism by which PGDPs participate in alterations in lipid metabolism induced by high-fat diet (HFD) feeding has not been elucidated. (2) Methods: Mice deficient in PGDP (GCGKO) and control mice were fed HFD for 7 days and analyzed, and differences in lipid metabolism in the liver, adipose tissue, and duodenum were investigated. (3) Results: GCGKO mice under HFD showed lower expression levels of the genes involved in free fatty acid (FFA) oxidation such as Hsl, Atgl, Cpt1a, Acox1 (p < 0.05), and Pparα (p = 0.05) mRNA in the liver than in control mice, and both FFA and triglycerides content in liver and adipose tissue weight were lower in the GCGKO mice. On the other hand, phosphorylation of hormone-sensitive lipase (HSL) in white adipose tissue did not differ between the two groups. GCGKO mice under HFD exhibited lower expression levels of Pparα and Cd36 mRNA in the duodenum as well as increased fecal cholesterol contents compared to HFD-controls. (4) Conclusions: GCGKO mice fed HFD exhibit a lesser increase in hepatic FFA and triglyceride contents and adipose tissue weight, despite reduced β-oxidation in the liver, than in control mice. Thus, the absence of PGDP prevents dietary-induced fatty liver development due to decreased lipid uptake in the intestinal tract.
摘要：
（1）背景：胰高血糖素原衍生肽（PDGP）包括胰高血糖素（Gcg），GLP-1和GLP-2调节肝脏中的脂质代谢，脂肪细胞,和肠。然而,PGDPs参与高脂饮食（HFD）喂养引起的脂质代谢改变的机制尚未阐明。(2)方法:PGDP缺陷小鼠(GCGKO)和对照小鼠饲喂HFD7天,和肝脏脂质代谢的差异，脂肪组织,和十二指肠进行了调查。（3）结果：HFD下的GCGKO小鼠显示出参与游离脂肪酸（FFA）氧化的基因如Hsl的较低表达水平。Atgl,Cpt1a,Acox1（p<0.05），与对照组小鼠相比，肝脏中的Pparα（p=0.05）mRNA，GCGKO小鼠肝脏和脂肪组织重量中的FFA和甘油三酯含量均较低。另一方面,白色脂肪组织中激素敏感性脂肪酶(HSL)的磷酸化在两组之间没有差异.与HFD-对照相比,HFD下的GCGKO小鼠在十二指肠中表现出较低的Pparα和Cd36mRNA表达水平以及增加的粪便胆固醇含量。（4）结论：HFD喂养的GCGKO小鼠肝脏FFA和甘油三酯含量以及脂肪组织重量增加较少，尽管肝脏中的β-氧化减少，比对照小鼠。因此，缺乏PGDP可以防止饮食诱导的脂肪肝发展，这是由于肠道脂质吸收减少。
