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

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.

The link between the AMPK/SIRT1 axis and a flavonoid‐rich extract of Citrus bergamia juice: A cell‐free, in silico, and in vitro study

“…Some flavonoids assessed here have been studied for their properties on activating AMPK pathway. The treatment with NAR (Zygmunt, Faubert, MacNeil, & Tsiani, ), NRG (Sui, Xiao, Lu, & Sun, ), or NHP (Wu et al, ) was shown to positively act on AMPK both in vitro and in vivo models. HSP and NER were not investigated in these regards.…”

“…Some flavonoids assessed here have been studied for their properties on activating AMPK pathway. The treatment with NAR(Zygmunt, Faubert, MacNeil, & Tsiani, 2010), NRG(Sui, Xiao, Lu, & Sun, 2018), or NHP(Wu et al, 2017) was FIGURE 7 AMPK is implied in the activation of SIRT1 induced by BJe. THP-1 cells were treated with BJe or AICAR for 1 h, prior adding lipopolysaccharide (LPS).…”

Naringin Attenuates High Fat Diet Induced Non-alcoholic Fatty Liver Disease and Gut Bacterial Dysbiosis in Mice

“…The normal chow diet (ND, 1025), the ND supplemented with 0.07% NAR (Sigma-Aldrich, St. Louis, MO, United States), the HFD (synthetic diet supplemented with 0.15% cholesterol, w/w and 41% energy from fat, H10141), and the HFD supplemented with 0.07% NAR were purchased from Beijing HFK Bioscience Co., Ltd. (Beijing, China). The dose of 0.07% NAR is based on previous studies (Wang et al, 2015;Sui and Xiao, 2018). After 1 week of acclimation on ND, the mice were randomly divided into the ND group (n = 20) and the HFD group (n = 20) and treated for 8 weeks.…”

The Study of the Response of Fat Metabolism to Long-Term Energy Stress Based on Serum, Fatty Acid and Transcriptome Profiles in Yaks

“…Adenosine monophosphate-activated protein kinase (AMPK) has a central role in the regulation of energy metabolism [ 46 , 47 ]. The serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform (PP2A) can inhibit the activation of AMPK by dephosphorylation, and the expression of its gene, PPP2R1A, was downregulated in the subcutaneous fat of the yaks under ES ( q < 0.01).…”