scholarly journals Effect of Adrenergic Agonists on High-Fat Diet-Induced Hepatic Steatosis in Mice

2020 ◽  
Vol 21 (24) ◽  
pp. 9392
Author(s):  
Yukiomi Nakade ◽  
Rena Kitano ◽  
Taeko Yamauchi ◽  
Satoshi Kimoto ◽  
Kazumasa Sakamoto ◽  
...  

The autonomic nervous system, consisting of sympathetic and parasympathetic branches, plays an important role in regulating metabolic homeostasis. The sympathetic nervous system (SNS) regulates hepatic lipid metabolism by regulating adrenergic receptor activation, resulting in the stimulation of hepatic very-low-density lipoprotein-triglyceride (TG) production in vivo. However, only a few studies on the relationship between SNS and hepatic steatosis have been reported. Here, we investigate the effect of adrenergic receptor agonists on hepatic steatosis in mice fed a high-fat diet (HFD). The α-adrenergic receptor agonist phenylephrine (10 mg/kg/d) or the β-adrenergic receptor agonist isoproterenol (30 mg/kg/d) was coadministered with HFD to male mice. After five weeks, hepatic steatosis, TG levels, and hepatic fat metabolism-related biomarkers were examined. HFD treatment induced hepatic steatosis, and cotreatment with phenylephrine, but not isoproterenol, attenuated this effect. Phenylephrine administration upregulated the mRNA levels of hepatic peroxisome proliferator-activated receptor alpha and its target genes (such as carnitine palmitoyltransferase 1) and increased hepatic β-hydroxybutyrate levels. Additionally, phenylephrine treatment increased the expression of the autophagosomal marker LC3-II but decreased that of p62, which is selectively degraded during autophagy. These results indicate that phenylephrine inhibits hepatic steatosis through stimulation of β-oxidation and autophagy in the liver.

RSC Advances ◽  
2017 ◽  
Vol 7 (60) ◽  
pp. 37858-37866 ◽  
Author(s):  
Lingling Luo ◽  
Yin Li ◽  
Dongshan Wang ◽  
Yuanyuan Zhao ◽  
Yahui Wang ◽  
...  

Ginkgolide B (GB) is a natural occurring terpene lactone and a selective agonistic ligand of hPXR.


Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2114 ◽  
Author(s):  
Leonardo de Souza Mesquita ◽  
Cíntia Caria ◽  
Paola Santos ◽  
Caio Ruy ◽  
Natalia da Silva Lima ◽  
...  

No scientific report proves the action of the phytochemicals from the mangrove tree Rhizophora mangle in the treatment of diabetes. The aim of this work is to evaluate the effects of the acetonic extract of R. mangle barks (AERM) on type 2 diabetes. The main chemical constituents of the extract were analyzed by high-performance liquid chromatography (HPLC) and flow injection analysis electrospray-iontrap mass spectrometry (FIA-ESI-IT-MS/MS). High-fat diet (HFD)-fed mice were used as model of type 2 diabetes associated with obesity. After 4 weeks of AERM 5 or 50 mg/kg/day orally, glucose homeostasis was evaluated by insulin tolerance test (kiTT). Hepatic steatosis, triglycerides and gene expression were also evaluated. AERM consists of catechin, quercetin and chlorogenic acids derivatives. These metabolites have nutritional importance, obese mice treated with AERM (50 mg/kg) presented improvements in insulin resistance resulting in hepatic steatosis reductions associated with a strong inhibition of hepatic mRNA levels of CD36. The beneficial effects of AERM in an obesity model could be associated with its inhibitory α-amylase activity detected in vitro. Rhizophora mangle partially reverses insulin resistance and hepatic steatosis associated with obesity, supporting previous claims in traditional knowledge.


2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Ronald Barbaras ◽  
Rudi Baron ◽  
Marine Goffinet ◽  
Claudine Tardy ◽  
Nadia Boubekeur ◽  
...  

The F1-ATPase/P2Y13 receptor pathway has been involved in the regulation of the HDL uptake liver and disposition via the reverse cholesterol transport. CT1007900 is a novel selective P2Y13 receptor agonist that has been shown to enhance the HDL uptake that results in the increased secretion of the bile acid, bile cholesterol and bile phospholipid into the gallbladder in mice. In the present study, CT1007900 has been evaluated in three different animal models of atherosclerosis. In ApoE -/- flow cessation model, the administration of the drug decreased the cholesterol concentration in atherosclerotic plaques. In a high fat diet fed ApoE -/- mouse model, the prevention of the progression of the plaque in aorta was further evaluated after 4-week treatment with CT1007900. The treated animals had significant decreases in plaque area, cholesterol content, VCAM1 expression and macrophage content. In the high fat diet fed rabbits, 4-week treatment reduced the cholesterol content by about 30% and also decreased the thickness of the plaques. The ApoA1 mRNA levels in the liver and ApoA1 protein concentration in the plasma increased in the drug-treated animals. The HDL content of the treated animals showed a very consistent pattern with a specific decrease in large HDL and an increase of the “intermediate” size HDL particles as compared to control animals. These intermediate HDL particles seem to be more efficient particles for the removal of cholesterol from atherosclerotic plaques by increasing efflux of cholesterol from the macrophages present in the lesions. The plasma samples from drug treated rabbits showed a dose-dependent increase in the cholesterol efflux in an in vitro assay using J774 cells. These results clearly demonstrate that improving functionality of HDL rather than the levels of HDL could have a positive impact on the atherosclerotic pathology. These data also support that P2Y13 receptor agonists could be useful pharmacological therapeutics for the treatment of complications due to atherosclerotic disease.


2007 ◽  
Vol 293 (3) ◽  
pp. E819-E825 ◽  
Author(s):  
Hiroshi Iwakura ◽  
Takashi Akamizu ◽  
Hiroyuki Ariyasu ◽  
Taiga Irako ◽  
Kiminori Hosoda ◽  
...  

Obesity is characterized by markedly decreased ghrelin and growth hormone (GH) secretion. Ghrelin is a GH-stimulating, stomach-derived peptide that also has orexigenic action. Ghrelin supplement may restore decreased GH secretion in obesity, but it may worsen obesity by its orexigenic action. To reveal effects of ghrelin administration on obese animals, we first examined acute GH and orexigenic responses to ghrelin in three different obese and/or diabetic mouse models: db/db mice, mice on a high-fat diet (HFD mice), and Akita mice for comparison. GH responses to ghrelin were significantly suppressed in db/db, HFD, and Akita mice. Food intake of db/db and Akita mice were basally higher, and further stimulation of food intake by ghrelin was suppressed. Pituitary GH secretagogue receptor mRNA levels in db/db and HFD mice were significantly decreased, which may partly contribute to decreased GH response to ghrelin in these mice. In Akita mice for comparison, decreased hypothalamic GH-releasing hormone (GHRH) mRNA levels may be responsible for decreased GH response, since maximum GH response to ghrelin needs GHRH. When ghrelin was injected into HFD mice with GHRH coadministrated, GH responses to ghrelin were significantly emphasized. HFD mice injected with low-dose ghrelin and GHRH for 10 days did not show weight gain. These results indicate that low-dose ghrelin and GHRH treatment may restore decreased GH secretion in obesity without worsening obesity.


2014 ◽  
Vol 52 (01) ◽  
Author(s):  
JP Sowa ◽  
L Wingerter ◽  
G Gerken ◽  
M Palmert ◽  
A Canbay ◽  
...  

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