scholarly journals Loss of Glycine N-Methyltransferase Associates with Angiopoietin-Like Protein 8 Expression in High Fat-Diet-Fed Mice

2019 ◽  
Vol 20 (17) ◽  
pp. 4223 ◽  
Author(s):  
Jian-Wei Huang ◽  
Chao-Ju Chen ◽  
Chia-Hung Yen ◽  
Yi-Ming Arthur Chen ◽  
Yu-Peng Liu
Keyword(s):  
Metabolic Syndrome ◽  
High Fat Diet ◽  
Metabolic Diseases ◽  
Inverse Correlation ◽  
Microarray Dataset ◽  
Dominant Negative ◽  
Mechanistic Study ◽  
Dependent Manner ◽  
High Fat ◽  
High Insulin

Imbalance of lipid metabolism is a main cause of metabolic syndrome leading to life-threatening metabolic diseases. Angiopoietin-like protein 8 (Angptl8) was recently identified as a liver and adipose tissue-released hormone that is one of the molecules involved in triglyceride metabolism. However, the regulatory mechanism of Angptl8 is largely unknown. A high fat diet (HFD)-fed mouse model, which showed high cholesterol, high triglyceride, and high insulin in the blood, revealed the upregulation of hepatic and plasma Angptl8 and the downregulation of hepatic glycine N-methyltransferase (GNMT). The inverse correlation of hepatic Angptl8 and GNMT expression in the livers of HFD-fed mice was also confirmed in a publicly available microarray dataset. The mechanistic study using primary hepatocytes showed that the Angptl8 expression could be induced by insulin treatment in a dose- and time-dependent manner. Inhibition of PI3K/Akt pathway by the specific inhibitors or the dominant-negative Akt blocked the insulin-induced Angptl8 expression. Moreover, knockout of GNMT promoted the Akt activation as well as the Angptl8 expression. These results suggested that GNMT might be involved in insulin-induced Angptl8 expression in HFD-mediated metabolic syndrome.

Abstract 394: Posttranslational Modification Of Klf5 Mediates Metabolic Dysfunction And Vascular Disease In Metabolic Syndrome

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Yumiko Oishi ◽  
Ichiro Manabe ◽  
Kazuyuki Tobe ◽  
Takashi Kadowaki ◽  
Ryozo Nagai
Keyword(s):  
Skeletal Muscle ◽  
Metabolic Syndrome ◽  
Energy Expenditure ◽  
Posttranslational Modifications ◽  
High Fat Diet ◽  
Metabolic Diseases ◽  
C2c12 Myotubes ◽  
Metabolic Dysfunction ◽  
High Fat ◽  
Increased Risk

We have previously shown that a zinc finger transcription factor, Krüppel-like factor 5 (KLF5), plays an important role in pathogenesis of cardiovascular diseases, such as atherosclerosis. KLF5 heterozygous knockout ( KLF5 +/ − ) mice exhibited much less neointima formation, cardiac hypertrophy and fibrosis. We also found that expression of KLF5 correlated with a higher incidence of restenosis following PCI and the SNP located within the KLF5 promoter was associated with an increased risk of hypertension in man. Interestingly, KLF5 is also expressed in metabolic tissues such as adipose tissue, skeletal muscle, and pancreatic β-cells. Thus, we hypothesized that KLF5 might play a role in metabolic diseases. To test this, KLF5 +/ − mice were fed with high-fat diet. Although KLF5 +/ − mice ate more food than wild-type littermates, they were resistant to high-fat diet-induced obesity and protected from dyslipidemia, glucose intolerance and hepatic steatosis, indicating that KLF5 + /− mice were less susceptible to metabolic syndrome. The systemic O 2 consumption and expression of genes involved in energy expenditure in skeletal muscle were increased in KLF5 + /− mice, demonstrating enhanced energy expenditure, which partly explains the phenotype. Knocking down KLF5 by siRNA increased expression levels of UCP2/3 and CPT-1b in C2C12 myotubes, suggesting that KLF5 may inhibit energy expenditure-related genes. Chromatin immunoprecipitation and coimmunoprecipitation assays showed that KLF5 interacted with corepressors, such as SMRT and NCoR, and strongly inhibited the UCP and CPT-1b promoters. We found that this inhibitory activity of KLF5 depended on its SUMOylation. When KLF5 was deSUMOylated, it activated the promoters. These data demonstrate that KLF5 acts as a molecular switch for energy expenditure and the posttranslational modifications of KLF5 including SUMOylation turns on/off the switch function of KLF5. Given that KLF5 also controls tissue remodeling in response to external stress, KLF5 may mediate metabolic dysfunction and atherosclerosis in metabolic syndrome. Our findings also suggest that the posttranscriptional modification of KLF5 is an attractive novel therapeutic target.

scholarly journals Dietary nitrite reverses features of postmenopausal metabolic syndrome induced by high-fat diet and ovariectomy in mice

2017 ◽  
Vol 312 (4) ◽  
pp. E300-E308 ◽  
Author(s):  
Kazuo Ohtake ◽  
Nobuyuki Ehara ◽  
Hiroshige Chiba ◽  
Genya Nakano ◽  
Kunihiro Sonoda ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Visceral Fat ◽  
High Fat Diet ◽  
Hormone Replacement ◽  
Dependent Manner ◽  
High Fat ◽  
Alternative Source ◽  
Enos Activity

Menopausal women are at greater risk of developing metabolic syndrome with reduced endothelial nitric oxide synthase (eNOS) activity. Hormone replacement therapy increases eNOS activity and normalizes some characteristics of metabolic syndrome. We hypothesized that nitric oxide (NO) supplementation should have a therapeutic effect on this syndrome. We examined the effect of dietary nitrite in a mouse model with postmenopausal metabolic syndrome induced by ovariectomy (OVX) and a high fat diet (HF). C57BL/6 female mice were divided into five groups, sham+normal fat diet (NF), sham+ HF, OVX+HF with or without sodium nitrite (50 mg and 150 mg/l) in the drinking water. Daily food intake and weekly body weight were monitored for 18 wk. OVX and HF significantly reduced plasma levels of nitrate/nitrite (NOx), and mice developed obesity with visceral hypertrophic adipocytes and increased transcriptional levels of monocyte chemoattractant protein-1, TNF-α, and IL-6 in visceral fat tissues. The proinflammatory state in the adipocytes provoked severe hepatosteatosis and insulin resistance in OVX+HF group compared with sham+NF group. However, dietary nitrite significantly suppressed adipocyte hypertrophy and transcriptions of proinflammatory cytokines in visceral fat in a dose-dependent manner. The improvement of visceral inflammatory state consequently reversed the hepatosteatosis and insulin resistance observed in OVX+HF mice. These results suggest that an endogenous NO defect might underlie postmenopausal metabolic syndrome and that dietary nitrite provides an alternative source of NO, subsequently compensating for metabolic impairments of this syndrome.

scholarly journals Maternal High-Fat Diet Exposure During Gestation and Lactation Affects Intestinal Development in Suckling Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Monika Słupecka-Ziemilska ◽  
Paulina Grzesiak ◽  
Paweł Kowalczyk ◽  
Piotr Wychowański ◽  
Jarosław Woliński
Keyword(s):  
High Fat Diet ◽  
Metabolic Diseases ◽  
Maternal Diet ◽  
Dependent Manner ◽  
Intestinal Development ◽  
High Fat ◽  
Rat Pups ◽  
Diet Induced Obesity ◽  
Cholinergic Signaling ◽  
And Function

Maternal health and diet influence metabolic status and play a crucial role in the development of metabolic function in offspring and their susceptibility to metabolic diseases in adulthood. The pathogenesis of various metabolic disorders is often associated with impairment in intestinal structure and function. Thus, the aim of the current study was to determine the effects of maternal exposure to a high fat diet (HFD), during gestation and lactation, on small intestinal growth and maturation in rat pups at 21 days old. Female, Wistar Han rats were fed either a breeding diet (BD) or high fat diet (HFD), from mating until the 21st day of lactation. Maternal HFD exposure increased body weight, BMI and adiposity. Compared to the maternal BD, HFD exposure influenced small intestine histomorphometry in a segment-dependent manner, changed the activity of brush border enzymes and had an impact on intestinal contractility via changes in cholinergic signaling. Moreover, offspring from the maternal HFD group had upregulated mRNA expression of cyclooxygenase (COX)-2, which plays a role in the inflammatory process. These results suggest that maternal HFD exposure, during gestation and lactation, programs the intestinal development of the offspring in a direction toward obesity as observed changes are also commonly reported in models of diet-induced obesity. The results also highlight the importance of maternal diet preferences in the process of developmental programming of metabolic diseases.

scholarly journals TGR5 Expression Is Associated with Changes in the Heart and Urinary Bladder of Rats with Metabolic Syndrome

Life ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 695
Author(s):  
Chia-Chen Hsu ◽  
Kai-Chun Cheng ◽  
Yingxiao Li ◽  
Ping-Hao Hsu ◽  
Juei-Tang Cheng ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
High Fat Diet ◽  
Metabolic Diseases ◽  
Lithocholic Acid ◽  
Female Rats ◽  
High Fat ◽  
Tnf Α ◽  
G Protein Coupled ◽  
Camp Levels ◽  
Necrosis Factor

Adipose-derived cytokines may contribute to the inflammation that occurs in metabolic syndrome (MetS). The Takeda G protein-coupled receptor (TGR5) regulates energy expenditure and affects the production of pro-inflammatory biomarkers in metabolic diseases. Etanercept, which acts as a tumor necrosis factor (TNF)-α antagonist, can also block the inflammatory response. Therefore, the interaction between TNF-α and TGR5 expression was investigated in rats with high-fat diet (HFD)-induced obesity. Heart tissues isolated from the HFD-induced MetS rats were analyzed. Changes in TGR5 expression were investigated with lithocholic acid (LCA) as the agonist. Betulinic acid (BA) was used to activate TGR5 in urinary bladders. LCA was more effective in the heart tissues of HFD-fed rats, although etanercept alleviated the function of LCA. STAT3 activation and higher TGR5 expression were observed in the heart tissues collected from HFD-fed rats. Thus, cardiac TGR5 expression is promoted by HFD through STAT3 activation in rats. Moreover, the urinary bladders of female rats fed a HFD showed a low response, which was reversed by etanercept. Relaxation by BA in the bladders was more marked in HFD-fed rats. The high TGR5 expression in HFD-fed rats was characterized using a mRNA assay, and the increased cAMP levels were found to be stimulated by BA in the isolated bladders. Therefore, TGR5 expression increases with a HFD in both the hearts and urinary bladders. Collectively, cytokine-medicated TGR5 activation was observed in the hearts and urinary bladders of rats.

Abstract P257: High Fat Diet Induces Metabolic Syndrome-Like Phenotype Associated with Adverse Micro- and Macro-Vascular Remodeling

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Aaron J Trask
Keyword(s):  
Metabolic Syndrome ◽  
Blood Glucose ◽  
High Fat Diet ◽  
Vascular Remodeling ◽  
Coronary Flow ◽  
Metabolic Diseases ◽  
Fasting Blood Glucose ◽  
High Fat ◽  
Flow Reserve ◽  
Vascular Bed

Metabolic diseases such as type 2 diabetes (T2DM), hypertension, and metabolic syndrome (MetS) have been associated with vascular disease, and we have previously demonstrated vascular-bed-specific remodeling in both mouse and porcine models of T2DM and MetS. The aim of this study was to determine whether high-fat diet would induce MetS-associated adverse micro- and macro-vascular remodeling and mechanics in mice. Three week old male C57BL/6J mouse siblings were randomized to receive either a normal low-fat (LFD: 10% fat) or high-fat (HFD: 60% fat) diet for 20 weeks (n=7-10 per group). HFD induced a MetS-like phenotype characterized by increased body weight (LFD: 28.6±0.7 vs. HFD: 43.4±0.8 g, p <0.0001), increased mean arterial pressure (LFD: 65±3 vs. HFD: 91±2 mmHg, p <0.0001), increased plasma insulin (LFD: 106±39 vs. HFD: 368±54 pg/mL, p <0.001), and transient increases in fasting blood glucose. Passive pressure myography of septal coronary resistance microvessels (CRMs) revealed reduced internal (LFD: 151±11 vs. HFD: 113±7 μm at 125 mmHg, p <0.05) and external diameters, increased wall/lumen ratio (LFD: 5.5±0.6 vs. HFD: 7.8±0.5 at 125 mmHg, p <0.01) and reduced incremental modulus of elasticity (LFD: 7.9x10 6 ±1.7x10 6 vs. HFD: 4.5x10 6 ±0.6x10 6 dynes/cm 2 at 125 mmHg, p <0.01) in mice fed HFD. Adverse CRM remodeling was associated with reduced coronary flow at baseline and under hyperemic conditions, which reduced coronary flow reserve (LFD: 7.3±0.5 vs. HFD: 5.5±0.5, p <0.05). Aortic pulse wave velocity was increased (LFD: 0.31±0.02 vs. HFD: 0.36±0.01 cm/ms, p <0.05) and significantly correlated with the increased blood pressure (r=0.67, p<0.01). These data demonstrate that 20 weeks of a high-fat diet induces an early MetS-like pathophysiological state that is associated with vascular-bed-specific remodeling and alterations in vascular biomechanics. Furthermore, the presence of adverse vascular remodeling in the presence of an early MetS-like phenotype, but not overt MetS (i.e. in the presence of sustained elevation in fasting blood glucose), may suggest the presence of underlying sub-clinical disease during the early progression of metabolic syndrome.

scholarly journals Chinese Propolis Prevents Obesity and Metabolism Syndromes Induced by a High Fat Diet and Accompanied by an Altered Gut Microbiota Structure in Mice

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 959
Author(s):  
Yufei Zheng ◽  
Yuqi Wu ◽  
Lingchen Tao ◽  
Xi Chen ◽  
Trevor Joseph Jones ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
High Fat Diet ◽  
Metabolic Diseases ◽  
Liver Weight ◽  
Dependent Manner ◽  
Male Mice ◽  
High Fat ◽  
16S Rrna Analysis ◽  
Triglyceride Accumulation ◽  
Chinese Propolis

The increasing incidence of obesity poses a great threat to public health worldwide. Recent reports also indicate the relevance of obesity in metabolic diseases. Chinese propolis (CP), as a well-studied natural nutraceutical, has shown a beneficial effect on alleviating diabetes mellitus. However, few studies have investigated the effect of CP on weight management and energy balance. We examined the beneficial effects of dietary CP on weight in high-fat diet-fed female and male mice and determined whether CP alters gut microbiota. In this study, dietary CP supplementation reduces body weight and improves insulin resistance in high-fat diet (HFD)-fed mice in a dose-dependent manner. CP treatment also reverses liver weight loss and triglyceride accumulation in association with hepatic steatosis. The 16S rRNA analysis of gut microbiota demonstrated that CP treatment modulates the composition in HFD-fed mice. Our study also suggests that male mice were more sensitive to CP treatment than female mice. Taken together, CP supplementation reduces weight gain and reverses gut microbiome dysbiosis induced by HFD. Further, the effects of CP treatment on metabolic biomarkers and microbiome structure differ by gender.

Effects of dietary n-3 PUFA levels in early life on susceptibility to high-fat-diet-induced metabolic syndrome in adult mice

2020 ◽  
pp. 108578
Author(s):  
Dan-Dan Wang ◽  
Fang Wu ◽  
Ling-Yu Zhang ◽  
Ying-Cai Zhao ◽  
Cheng-Cheng Wang ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
High Fat Diet ◽  
Early Life ◽  
High Fat ◽  
Adult Mice

scholarly journals Extract of Wax Gourd Peel Prevents High-Fat Diet-Induced Hyperlipidemia in C57BL/6 Mice via the Inhibition of the PPARγPathway

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Ming Gu ◽  
Shengjie Fan ◽  
Gaigai Liu ◽  
Lu Guo ◽  
Xiaobo Ding ◽  
...  
Keyword(s):  
Blood Glucose ◽  
High Fat Diet ◽  
Target Genes ◽  
Metabolic Diseases ◽  
Body Weight Gain ◽  
Fasting Blood Glucose ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
High Fat ◽  
Wax Gourd

Wax gourd is a popular vegetable in East Asia. In traditional Chinese medicine, wax gourd peel is used to prevent and treat metabolic diseases such as hyperlipidemia, hyperglycemia, obesity, and cardiovascular disease. However, there is no experimental evidence to support these applications. Here, we examined the effect of the extract of wax gourd peel (EWGP) on metabolic disorders in diet-induced C57BL/6 obese mice. In the preventive experiment, EWGP blocked body weight gain and lowered serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), liver TG and TC contents, and fasting blood glucose in mice fed with a high-fat diet. In the therapeutic study, we induced obesity in the mice and treated with EWGP for two weeks. We found that EWGP treatment reduced serum and liver triglyceride (TG) contents and fasting blood glucose and improved glucose tolerance in the mice. Reporter assay and gene expression analysis showed that EWGP could inhibit peroxisome proliferator-activated receptorγ(PPARγ) transactivities and could decrease mRNA levels of PPARγand its target genes. We also found that HMG-CoA reductase (HMGCR) was downregulated in the mouse liver by EWGP. Our data suggest that EWGP lowers hyperlipidemia of C57BL/6 mice induced by high-fat diet via the inhibition of PPARγand HMGCR signaling.

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