Naringin Activates AMPK Resulting in Altered Expression of SREBPs, PCSK9, and LDLR To Reduce Body Weight in Obese C57BL/6J Mice

• DOI: 10.1021/acs.jafc.8b02696
• Publication Date: 2018-08-10T07:57:07Z
• Authors: Guo-Guang Sui; Hong-Bo Xiao; Xiang-Yang Lu; Zhi-Liang Sun
• Keywords: Male; 0301 basic medicine; 2. Zero hunger; Body Weight; Mice, Obese; Up-Regulation; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; AMP-Activated Protein Kinase Kinases; Liver; Receptors, LDL; Flavanones; Animals; Humans; Obesity; Proprotein Convertase 9; Sterol Regulatory Element Binding Protein 1; Protein Kinases; Triglycerides; Sterol Regulatory Element Binding Protein 2

Previous investigations have shown molecular cross-talk among activated adenosine monophosphate-activated protein kinase (AMPK), proprotein convertase subtilisin/kexin type 9 (PCSK9), sterol regulatory element-binding proteins (SREBPs), and low-density lipoprotein receptor (LDLR) and that it may be an innovative pharmacologic objective for treating obesity. We scrutinized the beneficial effect of naringin, a flavanone-7- O-glycoside, on obesity and the mechanisms in the present study. We arbitrarily divided 50 mice into five groups ( n = 10): 25 or 50 or 100 mg/kg/day naringin-treated obese mice (gavage for 8 weeks), untreated obese mice, and C57BL/6J control. After 8 weeks, body weight was 51.8 ± 4.4 in the untreated obese mice group, while the weights were 41.4 ± 4.1, 34.6 ± 2.2, and 28.0 ± 2.3 in 25, 50,100 mg/kg naringin groups, respectively. Moreover, naringin treatment significantly decreased plasma 8-isoprostane (an indicator of the oxidative stress) level, fat weight, liver weight, hepatic total cholesterol concentration, hepatic triglyceride concentration, plasma leptin level, plasma insulin content, plasma low-density lipoprotein cholesterol level, and plasma PCSK9 production concomitantly with down-regulated expression of SREBP-2, PCSK9, and SREBP-1, and up-regulated expression of p-AMPKα and LDLR. The present results suggest that naringin activates AMPK resulting in altered expression of SREBPs, PCSK9, and LDLR to reduce the body weight of obese C57BL/6J mice.