Abstract 404: NLR Family, Pyrin Domain-containing 3 Knockout Rescues Cardiac Dysfunction Induced by High-fat Diet Feeding

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Matthew R Peterson ◽  
Samantha Haller ◽  
Tracy Ta ◽  
Luiza Bosch ◽  
Aspen Smith ◽  
...  

NLR family, pyrin domain-containing 3 (NLRP3) is a pattern recognition receptor responsible for perpetuating an inflammatory response through production of pro-inflammatory cytokines IL-1β and IL-18. It has been implicated in the sustained inflammatory response in obesity and multiple cardiovascular disease conditions. In order to investigate NLRP3 as a potential therapeutic target in metabolic syndrome, C57BL/6 wild-type (WT) and NLRP3 knockout (NLRP3-\-) mice were fed a normal diet (ND; 12% fat chow) or a high fat diet (HFD; 45% fat chow) for 5 months. At 5 months, echocardiography and glucose tolerance tests (GTTs) were performed. Cardiac function assessed by fractional shortening (FS) was significantly impaired by HFD feeding in the WT group (0.335 HFD vs. 0.456 ND; p<0.05) but not in the NLRP3-\- (0.449 HFD vs. 0.492 ND; p>0.05). FS was higher in NLRP3-\-HFD than in WT-HFD (p<0.05). Two-dimensional analysis shows the FS difference between NLRP3-\-HFD and WT-HFD was primarily explained by the difference in left ventricular end-systolic dimension (0.2716 cm WT vs. 0.1883 cm NLRP3-\-; p<0.05). Glucose tolerance measured by area under the curve (AUC) was significantly impaired by HFD feeding for both WT (23183 ND vs. 57298 HFD; p<0.001) and NLRP3-\- (23197 ND vs. 44626 HFD; p<0.001), but significantly better in the NLRP3-\-HFD than in WT-HFD (p<0.01). HFD feeding increased fasting blood glucose (FBG) for both WT (97.7 mg . dl -1 ND vs. 164.7 mg . dl -1 HFD; p<0.01) and NLRP3-\- (80.50 mg . dl -1 ND vs. 108.8 mg . dl -1 HFD; p<0.05), but significantly less in NLRP3-\- mice (NLRP3-\- vs. WT; p<0.05). For GTTs, body weight was significantly higher in the WT than NLRP3-\- fed HFD (47.93 g vs. 36.5 g; p<0.001). Body weight explained 92% of variation in glucose tolerance (p<0.0001) and 69% of variation in fasting blood glucose (p<0.0001). WT-HFD averaged 1.31X heavier than NLRP3-\-HFD, while the AUC for the IGTT was 1.28X larger for the WT-HFD than NLRP3-\-HFD. Body weights were not significantly different between genotypes at the time of echo. The results suggest that knockout of NLRP3 may be protective against HFD induced cardiovascular dysfunction. A protective effect on glucose tolerance is not strongly supported.

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Sumit Bhattacharyya ◽  
Leo Feferman ◽  
Terry Unterman ◽  
Joanne K. Tobacman

Aims. Major aims were to determine whether exposure to the commonly used food additive carrageenan could induce fasting hyperglycemia and could increase the effects of a high fat diet on glucose intolerance and dyslipidemia.Methods. C57BL/6J mice were exposed to either carrageenan, high fat diet, or the combination of high fat diet and carrageenan, or untreated, for one year. Effects on fasting blood glucose, glucose tolerance, lipid parameters, weight, glycogen stores, and inflammation were compared.Results. Exposure to carrageenan led to glucose intolerance by six days and produced elevated fasting blood glucose by 23 weeks. Effects of carrageenan on glucose tolerance were more severe than from high fat alone. Carrageenan in combination with high fat produced earlier onset of fasting hyperglycemia and higher glucose levels in glucose tolerance tests and exacerbated dyslipidemia. In contrast to high fat, carrageenan did not lead to weight gain. In hyperinsulinemic, euglycemic clamp studies, the carrageenan-exposed mice had higher early glucose levels and lower glucose infusion rate and longer interval to achieve the steady-state.Conclusions. Carrageenan in the Western diet may contribute to the development of diabetes and the effects of high fat consumption. Carrageenan may be useful as a nonobese model of diabetes in the mouse.


2021 ◽  
Author(s):  
Guijiao Xie ◽  
Zelin Liu ◽  
Jiao Wang ◽  
Shasha He ◽  
Honghong Liu ◽  
...  

Abstract Objective: To investigate the effects of hydrogen-rich water (HGRW) on the structure and composition of intestinal microflora in mice fed high-fat diets (HFDs). Materials and Methods : C57BL/6 mice were divided into four groups: (1) normal diet (CD)-normal water (W); (2) CD-HGRW; (3) HFD-W; and (4) HFD-HGRW. After 12 weeks, we sampled fasting blood glucose, lipids, transaminases, and tissue oxidative stress levels and measured body weight. High-throughput sequencing technology was used to sequence the intestinal microflora and differences in intestinal microflora were compared by group, using bioinformatics analysis. Results: Body weight, oral glucose tolerance, and blood glucose increased significantly in the HFD group compared with the CD group (P < 0.001), and malondialdehyde levels were significantly increased in the livers of mice fed a HFD (P < 0.05). Steatosis was seen in the liver parenchyma of the HFD group, and to a lesser degree in the HGRW group. The richness and diversity of intestinal flora only decreased significantly in the HFD group (P < 0.05). However, 24 genera and 26 species were significantly different between the HFD and CD subgroups of mice fed HGRW. Nine genera and five species were significantly different between the HGRW and W subgroups of mice fed a HFD. Correlations were confirmed for 10 physiological parameters; and were positively correlated with 17 genera in the HFD group; six genera were negatively correlated in the HGRW group. Importantly, Lactobacillus was closely related to tissue malondialdehyde levels. Conclusion: Oral HGRW has beneficial effects against antioxidant stress and liver damage. It may improve the diversity and structure of the intestinal flora, enhancing the relative abundance of beneficial flora.


10.5219/1136 ◽  
2019 ◽  
Vol 13 (1) ◽  
pp. 644-650 ◽  
Author(s):  
Ahdiyatul Fauza ◽  
Ahmad Ni'matullah Al-Baarri ◽  
Kis Djamiatun

T2DM has increase in global-morbidity and mortality. Oxidative stress and adiponectin-levels are important for insulin-resistance and pancreatic-b-cell-dysfunction in T2DM. Okra fruit is rich of quercetin and phytosterol which have positive-effect for T2DM. Research aimed was to study the effect of okra-flour to adiponectin-levels and total-antioxidant-capacity (TAC) in T2DM. Thirty Wistar-rats were divided randomly in five groups. K1 and (X1, X2 and X3)-treated-groups were in T2DM-condition-induced by high-fat-diet-(HFD)-Streptozotochin-(STZ)-nicotinamid-(NA). Healthy-controls-(K2)-group was also used. Okra-flour was given orally for 28 days at doses of 0.1; 0.2 and 0.3 g/Kg-body-weight/d to X1, X2 and X3-groups, respectively. Statistical program was used to analyse the different between pre-post-intervention, and between groups. Correlations between variables were also analysed. The serum-adiponectin and TAC-levels were measured by ELISA and ABTS-methods, respectively. By comparing pre and post-intervention, adiponectin levels of all-intervention-(X1, X2, X3)-group were  increase (p = 0.027 for X1 and X2; p = 0.028 for X3), while in the same period the decrease were found in group K1 (p = 0.026) and K2 (p = 0.028). Increase-TAC-levels pre-post-intervention was observed in group all-intervention-groups (p = 0.027), while no change in K1 (p = 0.66) and the decrease in group K2 (p = 0.039). Reduce-fasting-blood-glucose-levels pre-post-intervention were shown in the all-intervention-groups (p = 0.028), while for the K1 groups was increase (p = 0.028). There were significant differences between the five-groups on fasting-blood-glucose-levels, adiponectin and TAC-levels, and X3-group showed the highest adiponectin and TAC-levels. Very-strong-correlations were found between glucose-adiponectin-TAC-levels-post-intervention. Okra-flour make better glucose-adiponectin and TAC-levels in T2DM-conditions. Okra dose of 0.30 g/Kg-body-weight/day is the best in increasing adiponectin and TAC-levels.


Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Caleb J Worker ◽  
Wencheng Li ◽  
Yumei Feng

We recently reported that the (pro)renin receptor (PRR) is a key component of the brain renin-angiotensin system, mediating the majority of Ang II formation, and plays a pivotal role in the development of hypertension. Its importance in obesity-related metabolic syndrome is, however, unknown. We hypothesize that brain PRR plays a regulatory role in high-fat diet (HFD) induced metabolic syndrome. To test our hypothesis, neuron-specific PRR knockout (PRRKO) mice and wildtype (WT) littermates were fed with either HFD (60% calories from fat) or normal fat chow (NFD, 10% calories from fat) with matching calories for 16 weeks. Weekly body weight (BW) and monthly fasting blood glucose (FBG) measurements were recorded and end point glucose tolerance (GTT) and insulin sensitivity tests (IST) were performed. Blood pressure (BP) was recorded using radiotelemetry in conscious free moving mice. We observed no difference in BW or food intake between genotypes in either HFD or NFD. The baseline BP and heart rate (HR) were similar between PRRKO and WT mice; however, following 16 weeks HFD the BP (101±6 vs. 111±3 mmHg, P=0.035) and HR (536±12 vs. 578±4 BPM, P=0.046) were significantly lower in PRRKO compared with WT mice. Interestingly, neuronal PRR deletion attenuated the elevation of FBG (127.12±10.46 vs. 167.77±16.57 mg/dl, P=0.039) induced by HFD. Glucose tolerance was significantly improved in PRRKO compared with WT following 16 weeks of HFD (AUC: 20557±894 vs. 29994±2976, P=0.006), while there was no difference in the IST between the groups. We also found that HFD mice had higher levels of plasma (pro)renin (9.95±1.83 vs. 2.74± 0.47 ng/ml, P=0.005) and brain angiotensin II (656.8±94.9 vs. 375.3±32.0 pg/g, P=0.02), as well as higher cardiac (ΔHR to propranolol: -150±6 vs. -82±15 bpm , P=0.0054) and vasomotor (ΔBP to chlorisondamine: -44±3 vs. -22±3 mmHg, P=0.0004) sympathetic tone, suggesting that the HFD-induced rise in BP is sympathetically mediated and associated with elevation of brain angiotensin II. Our data indicates that PRR deletion in the neurons protects against glucose intolerance and BP elevation in HFD mice with no effect on insulin sensitivity or body weight. We conclude that neuronal PRR plays a role in the development of obesity-related metabolic syndrome.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
James Miller ◽  
Madison N Putich ◽  
Jennifer E Mueller ◽  
Aubrey O'Farrell ◽  
Samira Sholami ◽  
...  

Abstract Objectives Metabolic syndrome (MetS) is an important risk factor for cardiovascular mortality and vascular inflammation plays a major role in the development of vascular complications. We tested the hypothesis that dietary strawberries (SB) attenuate vascular inflammation in MetS and this is due to a direct effect of SB on the vasculature. Methods Seven-week-old male C57BL/6 J mice consumed rodent diets with 10% kcal from fat (control diet fed mice; CD) or 60% kcal from fat (high-fat diet fed mice; HFD) for 12 weeks and subgroups of CD and HFD mice were fed a 2.35% freeze-dried SB supplemented diet (CD + SB or HFD + SB). This dose in mice is equivalent to two servings of SB (∼160 g) per day in humans. HFD model shares many vascular phenotypes with human MetS including vascular inflammation. The following analyses were completed after 12-week treatment: body weight; food intake; body composition; respiratory exchange ratio (RER), energy expenditure and activity (in light and dark cycle by Comprehensive Laboratory Animal Monitoring System); fasting and non-fasting blood glucose; glucose and insulin tolerance tests; and vascular inflammation (binding of fluorescent labelled mouse monocytes WEHI78/24 to aortic vessel). Results HFD mice exhibited increased body weight, reduced lean body mass, increased body fat, reduced RER (in both light and dark cycle), increased fasting and non-fasting blood glucose, and impaired glucose and insulin tolerance compared to CD mice (P < 0.05). SB supplementation does not alter body weight, body fat, lean body mass, blood glucose, glucose or insulin tolerance in CD + SB and HFD + SB mice. The energy expenditure and activity were similar among the groups. The aortic vessel from HFD exhibited an increased binding to WEHI 78/24 monocytic cells vs CD mice. However, SB supplementation reduced monocyte binding to the vessel in HFD + SB vs HFD mice (P < 0.05). Conclusions Strawberry supplementation improves vascular inflammation in HFD mice without altering metabolic milieu. This study indicates that the beneficial vascular effects of SB may not be due to a secondary effect but could be a direct effect on the vasculature. Strawberry consumption may be a potential adjunct strategy to prevent vascular complications in MetS. Funding Sources USDA grant (to ABPV), University of Utah Undergraduate Research Opportunity Program Award (to MNP, JEM, ASO, SS).


2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Ming Gu ◽  
Shengjie Fan ◽  
Gaigai Liu ◽  
Lu Guo ◽  
Xiaobo Ding ◽  
...  

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.


Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 302
Author(s):  
Ahtesham Hussain ◽  
Jin Sook Cho ◽  
Jong-Seok Kim ◽  
Young Ik Lee

Background: Currently, obesity is a global health challenge due to its increasing prevalence and associated health risk. It is associated with various metabolic diseases, including diabetes, hypertension, cardiovascular disease, stroke, certain forms of cancer, and non-alcoholic liver diseases (NAFLD). Objective: The aim of this study to evaluate the effects of polyphenol enriched herbal complex (Rubus crataegifolius/ellagic acid, Crataegus pinnatifida Bunge/vitexin, chlorogenic acid, Cinnamomum cassiaa/cinnamic acid) on obesity and obesity induced NAFLD in the high-fat diet (HFD)-induced obese mouse model. Methods: Obesity was induced in male C57BL/6 mice using HFD. After 8 weeks, the mice were treated with HFD+ plants extract for 8 weeks. Body weight, food intake weekly, and blood sugar level were measured. After sacrifice, changes in the treated group’s liver weight, fat weight, serum biochemical parameters, hormone levels, and enzyme levels were measured. For histological analysis, tissues were stained with hematoxylin-eosin (H&E) and Oil Red-O. Results: Our results showed that the herbal complex ameliorated body weight and liver weight gain, and decreased total body fat in HFD-fed animals. Post prandial blood glucose (PBG) and fasting blood glucose (FBG) were lower in the herbal complex-treated group than in the HFD control group. Additionally, herbal formulation treatment significantly increased HDL levels in serum and decreased TC, TG, AST, ALT, deposition of fat droplets in the liver, and intima media thickness (IMT) in the aorta. Herbal complex increased serum adiponectin and decreased serum leptin. Herbal complex also increased carnitine palmityl transferase (CPT) activity and significantly decreased enzyme activity of beta-hydroxy beta methyl glutamyl-CoA (HMG-CoA) reductase, and fatty acid synthase (FAS). Conclusions: The results of this study demonstrated that the herbal complex is an effective herbal formulation in the attenuation of obesity and obesity-induced metabolic dysfunction including NAFLD in HFD-induced mouse model.


2014 ◽  
Vol 92 (5) ◽  
pp. 405-417 ◽  
Author(s):  
Xian-Wei Li ◽  
Yan Liu ◽  
Wei Hao ◽  
Jie-Ren Yang

Sequoyitol decreases blood glucose, improves glucose intolerance, and enhances insulin signaling in ob/ob mice. The aim of this study was to investigate the effects of sequoyitol on diabetic nephropathy in rats with type 2 diabetes mellitus and the mechanism of action. Diabetic rats, induced with a high-fat diet and a low dose of streptozotocin, and were administered sequoyitol (12.5, 25.0, and 50.0 mg·(kg body mass)−1·d−1) for 6 weeks. The levels of fasting blood glucose (FBG), serum insulin, blood urea nitrogen (BUN), and serum creatinine (SCr) were measured. The expression levels of p22phox, p47phox, NF-κB, and TGF-β1 were measured using immunohistochemisty, real-time PCR, and (or) Western blot. The total antioxidative capacity (T-AOC), as well as the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) were also determined. The results showed that sequoyitol significantly decreased FBG, BUN, and SCr levels, and increased the insulin levels in diabetic rats. The level of T-AOC was significantly increased, while ROS and MDA levels and the expression of p22phox, p47phox, NF-κB, and TGF-β1 were decreased with sequoyitol treatment both in vivo and in vitro. These results suggested that sequoyitol ameliorates the progression of diabetic nephropathy in rats, as induced by a high-fat diet and a low dose of streptozotocin, through its glucose-lowering effects, antioxidant activity, and regulation of TGF-β1 expression.


2017 ◽  
Vol 52 (3) ◽  
pp. 174
Author(s):  
Purwo Sri Rejeki ◽  
Harjanto Harjanto ◽  
Raden Argarini ◽  
Imam Subadi

The aim of this study was to determine the comparative effects of EA (EA) on the CV12, ST36 and ST40 to weight gain prevention over the short-term regulation of energy balance. The study was conducted with a completely randomized design. Rats were divided into five groups: negative control group (no treatment, n=5), positive control (sham EA/back, n=5), EA CV 12 (n=6), EA ST 36 (n=6) and EA ST 40 (n=7). Rats were exposed to high-fat diet for two weeks and EA was simultaneously performed once daily, five days a week for two weeks with 2 Hz, for 10 minutes with continuous wave. Body weight, BMI, front limb circumference and rear were measured during study. Levels of blood glucose, cholesterol, triglycerides, LDL and HDL were measured at the end of the study; which reflects the short-term regulation of energy homeostasis. For weight loss, EA CV12, ST36 and ST40 group have lost weight significantly compared to the negative and positive control group. The ST40 group has a significant decrease than ST36 and CV12. The most significant decrease in BMI found in the ST40 group. EA did not affect blood glucose levels, but modulated blood lipid profile. In ST 40 group there was a significant decrease in cholesterol, LDL and triglycerides. EA at point ST 40 is potential in preventing increased body weight and BMI in rats exposed to high-fat diet compared to the CV 12 and ST 36. ST 40 is a point with a potential of lowering LDL and triglycerides serum so that it can play a role in the short term regulation of energy homeostasis but also in the prevention of dyslipidemia.


Sign in / Sign up

Export Citation Format

Share Document