Morus alba L. Diminishes visceral adiposity, insulin resistance, behavioral alterations via regulation of gene expression of leptin, resistin and adiponectin in rats fed a high-cholesterol diet

2019 ◽  
Vol 201 ◽  
pp. 1-11 ◽  
Author(s):  
Fateheya Mohamed Metwally ◽  
Hend Rashad ◽  
Asmaa Ahmed Mahmoud

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Alex Sotolongo ◽  
Yi-Zhou Jiang ◽  
John Karanian ◽  
William Pritchard ◽  
Peter Davies

Objective: One of the first clinically detectable changes in the vasculature during atherogenesis is the accumulation of cholesterol within the vessel wall. Hypercholesterolemia is characterized by dysfunctional endothelial-dependent vessel relaxation and impaired NOS3 function. Since DNA methylation at gene promoter regions strongly suppresses gene expression, we postulated that high-fat/high-cholesterol diet suppresses endothelial NOS3 through promoter DNA methylation. Methods: Domestic male pigs were fed control diet (CD) or isocaloric high fat and high cholesterol diet (HC; 12% fat and 1.5% cholesterol) for 2, 4, 8 or 12 weeks prior to tissue collection. Furthermore, to determine the effects of risk factor withdrawal, an additional group of swine received HC for 12 weeks and then CD for 8 weeks; a control group received HC continuously for 20 weeks. Endothelial cells were harvested from common carotid aorta. In parallel in vitro studies, cultured human aortic endothelial cells (HAEC) were treated with human LDL, GW3956 (LXR agonist) and RG108 (DNA methyltransferase [DNMT] inhibitor). In cells from both sources, DNA methylation at the NOS3 promoter was measured using methylation specific pyro sequencing, and endothelial gene expression was measured using RT PCR. Results: HC diet increased plasma cholesterol level from 75 mg/dl on CD to a plateau of about 540 mg/dl within 2 weeks. Endothelial NOS3 expression was significantly reduced (71±9 % of CD) after 4 weeks of HC, a level sustained at subsequent time points. Withdrawal of HC for 8 weeks did not recover NOS3 expression. After 12-week HC, the NOS3 promoter was hypermethylated. Withdrawal of HC did not reverse NOS3 promoter methylation. In vitro treatment of HAEC with human LDL (200 mg/dl total cholesterol) or GW3956 (5μM) suppressed NOS3 mRNA to 50% and 30% respectively, suggesting that LXR/RXR is involved in suppression of NOS3. Nitric oxide production was consistently suppressed by GW3959. Both could be reversed through inhibition of DNMTs by RG108. Conclusions: DNA methylation and LXR/RXR pathway can mediate the HC-suppression of endothelial NOS3. The study identifies novel pharmaceutical targets in treating endothelial dysfunction. Crosstalk between these pathways is under investigation.



1994 ◽  
Vol 7 (11) ◽  
pp. 1026-1030 ◽  
Author(s):  
Mitsue Notake ◽  
Yasushi Kondo ◽  
Hideki Nomura ◽  
Katsuji Nakano ◽  
Kanoo Hosoki ◽  
...  


Inflammation ◽  
2007 ◽  
Vol 30 (3-4) ◽  
pp. 105-117 ◽  
Author(s):  
Xiaoyan Dai ◽  
Xiang Ou ◽  
Xinrui Hao ◽  
Dongli Cao ◽  
Yaling Tang ◽  
...  


2015 ◽  
Vol 6 (2) ◽  
pp. 492-500 ◽  
Author(s):  
Seung-Min Lee ◽  
Hye Won Han ◽  
Seung Yun Yim

We sought to evaluate whether a soy milk and fiber mixture could improve high cholesterol diet-induced changes in gut microbiota and inflammation.





Endocrinology ◽  
2014 ◽  
Vol 155 (12) ◽  
pp. 4697-4705 ◽  
Author(s):  
Anisha A. Gupte ◽  
Omaima M. Sabek ◽  
Daniel Fraga ◽  
Laurie J. Minze ◽  
Satoru K. Nishimoto ◽  
...  

Nonalcoholic fatty liver disease, particularly its more aggressive form, nonalcoholic steatohepatitis (NASH), is associated with hepatic insulin resistance. Osteocalcin, a protein secreted by osteoblast cells in bone, has recently emerged as an important metabolic regulator with insulin-sensitizing properties. In humans, osteocalcin levels are inversely associated with liver disease. We thus hypothesized that osteocalcin may attenuate NASH and examined the effects of osteocalcin treatment in middle-aged (12-mo-old) male Ldlr−/− mice, which were fed a Western-style high-fat, high-cholesterol diet for 12 weeks to induce metabolic syndrome and NASH. Mice were treated with osteocalcin (4.5 ng/h) or vehicle for the diet duration. Osteocalcin treatment not only protected against Western-style high-fat, high-cholesterol diet-induced insulin resistance but substantially reduced multiple NASH components, including steatosis, ballooning degeneration, and fibrosis, with an overall reduction in nonalcoholic fatty liver disease activity scores. Further, osteocalcin robustly reduced expression of proinflammatory and profibrotic genes (Cd68, Mcp1, Spp1, and Col1a2) in liver and suppressed inflammatory gene expression in white adipose tissue. In conclusion, these results suggest osteocalcin inhibits NASH development by targeting inflammatory and fibrotic processes.



2014 ◽  
Vol 65 ◽  
pp. 213-218 ◽  
Author(s):  
Sung-Pil Jo ◽  
Jeong-Keun Kim ◽  
Young-Hee Lim


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