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

J Agric Food Chem. 2018 Aug 29;66(34):8983-8990. doi: 10.1021/acs.jafc.8b02696. Epub 2018 Aug 20.

Abstract

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.

Keywords: AMP-activated protein kinase; C57BL/6J; naringin; obesity.

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Flavanones / administration & dosage*
  • Humans
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Obesity / drug therapy*
  • Obesity / genetics
  • Obesity / metabolism
  • Obesity / physiopathology
  • Proprotein Convertase 9 / genetics*
  • Proprotein Convertase 9 / metabolism
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Receptors, LDL / genetics*
  • Receptors, LDL / metabolism
  • Sterol Regulatory Element Binding Protein 1 / genetics*
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Sterol Regulatory Element Binding Protein 2 / genetics*
  • Sterol Regulatory Element Binding Protein 2 / metabolism
  • Triglycerides / metabolism
  • Up-Regulation / drug effects

Substances

  • Flavanones
  • Receptors, LDL
  • Srebf1 protein, mouse
  • Srebf2 protein, mouse
  • Sterol Regulatory Element Binding Protein 1
  • Sterol Regulatory Element Binding Protein 2
  • Triglycerides
  • Protein Kinases
  • AMP-activated protein kinase kinase
  • Pcsk9 protein, mouse
  • Proprotein Convertase 9
  • naringin