柠檬苦素通过激活AMPK减轻高脂饲料诱导的小鼠肾损伤

doi:10.11843/j.issn.0366-6964.2023.04.037

Abstract

Abstract: The study aimed to investigate the protective effect of Limonin (LM) on kidney injury induced by high-fat diet in mice. Twenty-five male C57BL/6 mice weighed 21-23 g were selected and randomly divided into five groups (n=5) according to the test requirements:control group, LM group, high-fat group, high-fat + low-dose LM group (60 mg·(kg·d)^-1) and high-fat+high-dose LM group (120 mg·(kg·d)^-1). After 12 weeks the body weight of mice were detected. The automatic biochemical analyzer was used to measure triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), creatinine (Cr), and urea nitrogen (BUN) in serum. The kits were used to measure TC, TG in the kidney. Hematoxylin-eosin (HE) and periodic acid-schiff (PAS) staining were performed to observe histological changes of kidney tissues. The protein expression of fatty acid synthase (FAS), sterol regulatory element binding protein 1 (SREBP1), adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) in the kidney were measured by immunohistochemistry. The protein expression of AMP-activated protein kinase (AMPK), phosphorylated AMPK (P-AMPK), FAS, SREBP1, ATGL, HSL and kidney injury molecule 1 (KIM1) was measured by immunoblot. The bound ability of LM、AICA Riboside (AICAR) and Dorsomorphin(Compound C) with AMPK was examined by molecular docking. The results showed that compared with high-fat group, LM intervention significantly reduced TG content in serum and kidney (P<0.05), improved histopathological kidney injury in mice fed with high-fat diet, promoted AMPK phosphorylation (P<0.05), significantly up-regulated the protein expression of ATGL and HSL (P<0.05), and inhibited the protein expression of SREBP1 and FAS (P<0.05). In addition, molecular docking showed that LM could bind tightly to AMPK proteins and had multiple sites identical to those of AICAR binding AMPK. The results suggest that LM attenuates kidney fat ectopic deposition and improves the high-fat diet-incluced kidney injury in mice by activating AMPK.

Key words: Limonin, high-fat diet, kidney injury, AMP-activated protein kinase

CLC Number:

S854

NIE Tong, MA Jun. Limonin Attenuates High-fat Diet-induced Kidney Injury in Mice by Activating AMPK[J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(4): 1742-1750.

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Limonin Attenuates High-fat Diet-induced Kidney Injury in Mice by Activating AMPK

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