AIM To investigate the effects of linagliptin treatment on hepatic energy metabolism and ER stress in high-fat-fed C57BL/6 mice. METHODS Forty male C57BL/6 mice, three months of age, received a control diet (C, 10% of lipids as energy, n = 20) or high-fat diet (HF, 50% of lipids as energy, n = 20) for 10 weeks. The groups were randomly subdivided into four groups to receive linagliptin, for five weeks, at a dose of 30 mg/kg/day added to the diets: C, C-L, HF, and HF-L groups. RESULTS The HF group showed higher body mass, total and hepatic cholesterol levels and total and hepatic triacylglycerol levels than the C group, all of which were significantly diminished by linagliptin in the HF-L group. The HF group had higher hepatic steatosis than the C group, whereas linagliptin markedly reduced the hepatic steatosis (less 52%, P < 0.001). The expression of Sirt1 and Pgc1a was more significant in the HF-L group than in the HF group. Linagliptin also elicited enhanced GLP-1 concentrations and a reduction in the expression of the lipogenic genes Fas and Srebp1c. Besides, HF-L showed a reduction in the genes related to endoplasmic reticulum stress Chop, Atf4, and Gadd45 coupled with reduced apoptotic nuclei immunostaining. CONCLUSION Linagliptin caused a marked reduction in hepatic steatosis as a secondary effect of its glucose-lowering property. NAFLD countering involved reduced lipogenesis, increased beta-oxidation, and relief in endoplasmic reticulum stress, leading to reduced apoptosis and better preservation of the hepatic structure. Therefore, linagliptin may be used, preferably in diabetic patients, to avoid the progression of hepatic steatosis.

中文翻译：

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抗硬脂酸利格列汀的多效性作用包括抑制高脂喂养小鼠的新生脂肪生成和内质网应激。

目的研究利格列汀治疗对高脂喂养的C57BL / 6小鼠肝能量代谢和内质网应激的影响。方法40只3个月大的雄性C57BL / 6小鼠接受对照饮食（C，能量为10％的脂质，n = 20）或高脂饮食（HF，能量为50％的脂质，n = 20）持续10周。这些组被随机分为四组，分别以30 mg / kg /天的剂量接受利格列汀，持续5周，分别为C，CL，HF和HF-L组。结果HF组显示出比C组更高的体重，总胆固醇和肝胆固醇水平以及总甘油三酯和肝甘油三酯水平，而HF-L组的利拉列汀均明显降低了所有这些指标。HF组的肝脂肪变性高于C组，而利那列汀则显着降低了肝脂肪变性（少于52％，P <0.001）。在HF-L组中Sirt1和Pgc1a的表达比在HF组中更显着。利格列汀还引起增加的GLP-1浓度，并降低了致脂基因Fas和Srebp1c的表达。此外，HF-L显示与内质网应激Chop，Atf4和Gadd45有关的基因减少，同时凋亡核免疫染色减少。结论利格列汀引起肝脂肪变性明显降低，这是其降糖性能的次要作用。NAFLD对抗涉及减少脂肪生成，增加β氧化和减轻内质网应激，从而导致凋亡减少和肝结构更好的保存。因此，可以优选在糖尿病患者中使用利那列汀以避免肝脂肪变性的发展。