The Effect of Cinnamaldehyde on iNOS Activity and NO-Induced Islet Insulin Secretion in High-Fat-Diet Rats

Introduction. Obesity and insulin resistance are associated with alterations in nitric oxide level and insulin secretion. Previous studies demonstrated that cinnamaldehyde (CNMA) improved islet insulin secretion and restored nitric oxide (NO) level, but its underlying mechanisms have not been investigated. This study aimed to investigate the effect of CNMA on inducible nitric oxide synthase (iNOS) activity and NO-induced islet insulin secretion in high-fat-diet (HFD) treated rats. Materials and Methods. Forty male Wistar rats (12 weeks old) were randomly divided into four equal groups, namely, control, CNMA, HFD, and HFD + CNMA. Control and CNMA groups were treated with standard laboratory animals’ diet, while HFD and HDF + CNMA groups were fed with an HFD diet enriched with 25% W / W tail fat for 16 weeks. CNMA was administrated orally (20 mg/kg body weight, daily) during the study period. Islet insulin secretion and the inducible NOS activity in the presence or absence of L-NAME (NO synthase inhibitor, 5 mmol/L) were evaluated. Results. L-NAME-suppressed insulin secretion in control, HFD, and HFD + CNMA groups; however, in the CNMA group, it could not exhibit such effect ( P < 0.01 ). Islets of HFD-treated animals showed significantly higher iNOS activity than controls. CNMA treatment significantly suppressed iNOS activities in CNMA and HFD + CNMA groups compared with control and HFD, respectively. Conclusion. These results suggest that the beneficial effect of CNMA on insulin secretion might be due to its inhibitory effect on iNOS activity.

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Microinjection of l-glutamate into the nucleus ambiguus partially inhibits gastric motility through the NMDA receptor – nitric oxide pathway

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2013-0413 ◽

2014 ◽

Vol 92 (6) ◽

pp. 455-459 ◽

Cited By ~ 2

Author(s):

Hong-Zhao Sun ◽

Shu-Zhen Zhao ◽

Hong-Bin Ai

Keyword(s):

Nitric Oxide ◽

Nmda Receptor ◽

Gastric Motility ◽

Inhibitory Effect ◽

Nmda Receptor Antagonist ◽

Nucleus Ambiguus ◽

No Donor ◽

Gastric Smooth Muscle ◽

Male Wistar Rats ◽

Synthase Inhibitor

We have previously reported that both l-glutamate (l-Glu) and nitric oxide (NO) modulate gastric motility in the nucleus ambiguus (NA). The aim of this study is to explore the potential correlation between the l-Glu and NO. A latex balloon connected to a pressure transducer was inserted into the pylorus through the fundus of anesthetized male Wistar rats to continuously record changes in gastric smooth muscle contractile curves. Pretreatment with the NO-synthase inhibitor N-nitro-l-arginine methylester (l-NAME) did not completely abolish the inhibitory effect of l-Glu on gastric motility, but intravenous injection of the ganglionic blocker hexamethonium bromide (Hb) did. By using a specific N-methyl-d-aspartic acid (NMDA) receptor antagonist, we blocked the inhibitory effect of the NO-donor sodium nitroprusside (SNP) on gastric motility. These results suggest that microinjections of l-Glu into the NA inhibits gastric motility by activating the cholinergic preganglionic neurons, partially through the NMDA receptor – NO pathway.

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Pengaruh Pemberian Ekstrak Anggur Laut terhadap Penurunan Kadar Kolesterol LDL Rattus norvegicus Jantan yang Mendapat Diet Tinggi Lemak

Hang Tuah Medical journal ◽

10.30649/htmj.v17i2.340 ◽

2020 ◽

Vol 17 (2) ◽

pp. 192

Author(s):

RONALDO LAU ◽

SULISTIANA PRABOWO ◽

RIAMI RIAMI

Keyword(s):

Cholesterol Level ◽

Rattus Norvegicus ◽

High Fat Diet ◽

Ldl Cholesterol ◽

White Male ◽

Standard Diet ◽

High Fat ◽

Caulerpa Racemosa ◽

Significant Difference ◽

Male Wistar Rats

ABSTRACTBackground: High fat diet increase the absorption of lipid in the intestinum, that can lead to increase LDL cholesterol level in the blood. Sea grapes extract (Caulerpa racemosa) contains antioxidant polyphenolic group that can reduce MTP and ACAT-2 in the body that can decrease LDL cholesterol level in the blood.The purpose of this study is to know the effect of sea grapes extract on decreasing LDL cholesterol of white male Wistar rats (Rattus norvegicus) fed with high fat diet.Method: 24 white male Wistar rats, that divided into 3 groups: 1) group of rats fed with standard diet for 28 days; 2) group of rats fed with high fat diet for 28 days; 3) group of rats fed with high fat diet for 28 days and given 10 gram/kg body weight/day of sea grapes extract on 15th-28th days. Then the blood LDL cholesterol level measured on the 29th day.Result : One-Way ANOVA Test showed there was significant difference (p=0.004) of LDL level between the group of rats fed with standard diet (12.37 mg/dl) compared to group of rats fed with high fat diet (17.87 mg/dl). There was significant difference (p=0.001) of LDL level between the group of rats fed with high fat diet (17.87 mg/dl) compared to group of rats fed with high fat diet and sea grapes extract (10.12 mg/dl).Conclusion: high fat diet significantly increase blood LDL cholesterol level and sea grapes extract (Caulerpa racemosa) significantly decrease blood LDL cholesterol level. Keywords :Sea grapes extract, LDL cholesterol, high fat diet

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Formononetin Ameliorates Cognitive Disorder via PGC-1α Pathway in Neuroinflammation Conditions in High-Fat Diet-Induced Mice

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527318666190807160137 ◽

2019 ◽

Vol 18 (7) ◽

pp. 566-577 ◽

Cited By ~ 4

Author(s):

Xinxin Fu ◽

Tingting Qin ◽

Jiayu Yu ◽

Jie Jiao ◽

Zhanqiang Ma ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

High Fat Diet ◽

Trifolium Pratense ◽

Amyloid Β ◽

Cognitive Disorder ◽

Mechanism Study ◽

High Fat ◽

Neuroprotective Effects ◽

Underlying Mechanisms

Background: Alzheimer’s disease is one of the most common neurodegenerative diseases in many modern societies. The core pathogenesis of Alzheimer’s disease includes the aggregation of hyperphosphorylated Tau and abnormal Amyloid-β generation. In addition, previous studies have shown that neuroinflammation is one of the pathogenesis of Alzheimer’s disease. Formononetin, an isoflavone compound extracted from Trifolium pratense L., has been found to have various properties including anti-obesity, anti-inflammation, and neuroprotective effects. But there are very few studies on the treatment of Alzheimer’s disease with Formononetin. Objective: The present study focused on the protective activities of Formononetin on a high-fat dietinduced cognitive decline and explored the underlying mechanisms. Methods: Mice were fed with HFD for 10 weeks and intragastric administrated daily with metformin (300 mg/kg) and Formononetin (20 and 40 mg/kg). Results: We found that Formononetin (20, 40 mg/kg) significantly attenuated the learning and memory deficits companied by weight improvement and decreased the levels of blood glucose, total cholesterol and triglyceride in high-fat diet-induced mice. Meanwhile, we observed high-fat diet significantly caused the Tau hyperphosphorylation in the hippocampus of mice, whereas Formononetin reversed this effect. Additionally, Formononetin markedly reduced the levels of inflammation cytokines IL-1β and TNF-α in high-fat diet-induced mice. The mechanism study showed that Formononetin suppressed the pro-inflammatory NF-κB signaling and enhanced the anti-inflammatory Nrf-2/HO-1 signaling, which might be related to the regulation of PGC-1α in the hippocampus of high-fat diet -induced mice. Conclusion: Taken together, our results showed that Formononetin could improve the cognitive function by inhibiting neuroinflammation, which is attributed to the regulation of PGC-1α pathway in HFD-induced mice.

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Repercussion of Maternal Diabetes and Post-Weaning High-Fat Diet Consumption in Laboratory Animals

Metabolism ◽

10.1016/j.metabol.2020.154652 ◽

2021 ◽

Vol 116 ◽

pp. 154652

Author(s):

Veronyca G. Paula ◽

Yuri K. Sinzato ◽

Rafaianne Q.M. Souza ◽

Larissa L. Cruz ◽

Eduardo Kloppel ◽

...

Keyword(s):

High Fat Diet ◽

Maternal Diabetes ◽

Laboratory Animals ◽

High Fat

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Gut Microbiome and Metabolome Profiles Associated with High-Fat Diet in Mice

Metabolites ◽

10.3390/metabo11080482 ◽

2021 ◽

Vol 11 (8) ◽

pp. 482

Author(s):

Jae-Kwon Jo ◽

Seung-Ho Seo ◽

Seong-Eun Park ◽

Hyun-Woo Kim ◽

Eun-Ju Kim ◽

...

Keyword(s):

Gut Microbiota ◽

Relative Abundance ◽

High Fat Diet ◽

Amplicon Sequencing ◽

Gas Chromatography Mass Spectrometry ◽

Control Group ◽

Rrna Gene ◽

High Fat ◽

Underlying Mechanisms ◽

Insight Into

Obesity can be caused by microbes producing metabolites; it is thus important to determine the correlation between gut microbes and metabolites. This study aimed to identify gut microbiota-metabolomic signatures that change with a high-fat diet and understand the underlying mechanisms. To investigate the profiles of the gut microbiota and metabolites that changed after a 60% fat diet for 8 weeks, 16S rRNA gene amplicon sequencing and gas chromatography-mass spectrometry (GC-MS)-based metabolomic analyses were performed. Mice belonging to the HFD group showed a significant decrease in the relative abundance of Bacteroidetes but an increase in the relative abundance of Firmicutes compared to the control group. The relative abundance of Firmicutes, such as Lactococcus, Blautia, Lachnoclostridium, Oscillibacter, Ruminiclostridium, Harryflintia, Lactobacillus, Oscillospira, and Erysipelatoclostridium, was significantly higher in the HFD group than in the control group. The increased relative abundance of Firmicutes in the HFD group was positively correlated with fecal ribose, hypoxanthine, fructose, glycolic acid, ornithine, serum inositol, tyrosine, and glycine. Metabolic pathways affected by a high fat diet on serum were involved in aminoacyl-tRNA biosynthesis, glycine, serine and threonine metabolism, cysteine and methionine metabolism, glyoxylate and dicarboxylate metabolism, and phenylalanine, tyrosine, and trypto-phan biosynthesis. This study provides insight into the dysbiosis of gut microbiota and metabolites altered by HFD and may help to understand the mechanisms underlying obesity mediated by gut microbiota.

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Vagotomy Reduces Insulin Clearance in Obese Mice Programmed by Low-Protein Diet in the Adolescence

Neural Plasticity ◽

10.1155/2017/9652978 ◽

2017 ◽

Vol 2017 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Camila Lubaczeuski ◽

Luciana Mateus Gonçalves ◽

Jean Franciesco Vettorazzi ◽

Mirian Ayumi Kurauti ◽

Junia Carolina Santos-Silva ◽

...

Keyword(s):

Insulin Secretion ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

High Fat Diet ◽

Insulin Clearance ◽

Protein Diet ◽

Low Protein Diet ◽

High Fat ◽

Insulin Degrading Enzyme ◽

Low Protein

The aim of this study was to investigate the effect of subdiaphragmatic vagotomy on insulin sensitivity, secretion, and degradation in metabolic programmed mice, induced by a low-protein diet early in life, followed by exposure to a high-fat diet in adulthood. Weaned 30-day-old C57Bl/6 mice were submitted to a low-protein diet (6% protein). After 4 weeks, the mice were distributed into three groups: LP group, which continued receiving a low-protein diet; LP + HF group, which started to receive a high-fat diet; and LP + HFvag group, which underwent vagotomy and also was kept at a high-fat diet. Glucose-stimulated insulin secretion (GSIS) in isolated islets, ipGTT, ipITT, in vivo insulin clearance, and liver expression of the insulin-degrading enzyme (IDE) was accessed. Vagotomy improved glucose tolerance and reduced insulin secretion but did not alter adiposity and insulin sensitivity in the LP + HFvag, compared with the LP + HF group. Improvement in glucose tolerance was accompanied by increased insulinemia, probably due to a diminished insulin clearance, as judged by the lower C-peptide : insulin ratio, during the ipGTT. Finally, vagotomy also reduced liver IDE expression in this group. In conclusion, when submitted to vagotomy, the metabolic programmed mice showed improved glucose tolerance, associated with an increase of plasma insulin concentration as a result of insulin clearance reduction, a phenomenon probably due to diminished liver IDE expression.

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The effects of quercetin on the expression of SREBP-1c mRNA in high-fat diet-induced NAFLD in mice

Journal of Basic and Clinical Physiology and Pharmacology ◽

10.1515/jbcpp-2020-0423 ◽

2021 ◽

Vol 32 (4) ◽

pp. 637-644

Author(s):

Jamal Nasser Saleh Al-maamari ◽

Mahardian Rahmadi ◽

Sisca Melani Panggono ◽

Devita Ardina Prameswari ◽

Eka Dewi Pratiwi ◽

...

Keyword(s):

High Fat Diet ◽

Fatty Liver Disease ◽

Inhibitory Effect ◽

Pcr Analysis ◽

Regulator Gene ◽

High Fat ◽

Alcoholic Fatty Liver ◽

Reverse Transcription Pcr ◽

Hematoxylin Eosin ◽

Alcoholic Fatty Liver Disease

Abstract Objectives The study aimed to determine the effect of quercetin on the expression of primary regulator gene involved in lipogenesis and triglycerides synthesis in the liver, and the sterol regulatory binding protein-1c (SREBP-1c) mRNA in non-alcoholic fatty liver disease (NAFLD) with a high-fat diet (HFD) model. Methods Fifty-six Balb/c mice were divided into seven groups: standard feed; HFD; HFD and quercetin 50 mg/kg for 28 days; HFD and quercetin 100 mg/kg BW for 28 days; HFD and quercetin 50 mg/kg for 14 days; HFD and quercetin 100 mg/kg for 14 days; HFD and repaired fed for 14 days. Quercetin was administered intraperitoneally. The animals were sacrificed 24 h after the last treatment; the liver was taken for macroscopic, histopathological staining using hematoxylin–eosin and reverse transcription-PCR analysis sample. Results HFD significantly increased the expression of SREBP-1c mRNA; meanwhile, quercetin and repaired feed significantly reduced the expression of SREBP-1c mRNA in the liver. Quercetin at a dose of 50 mg/kg and 100 mg/kg also improved liver cells’ pathological profile in high-fat diet NAFLD. Conclusions The present study suggests that quercetin has an inhibitory effect on SREBP-1c expression and improved liver pathology in NAFLD mice.

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IP6-assisted CSN-COP1 competition regulates a CRL4-ETV5 proteolytic checkpoint to safeguard glucose-induced insulin secretion

Nature Communications ◽

10.1038/s41467-021-22941-3 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Hong Lin ◽

Yuan Yan ◽

Yifan Luo ◽

Wing Yan So ◽

Xiayun Wei ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Secretion ◽

High Fat Diet ◽

E3 Ligase ◽

Human Islets ◽

Cop9 Signalosome ◽

Congenital Hyperinsulinism ◽

High Fat ◽

Transcriptional Suppressor

AbstractCOP1 and COP9 signalosome (CSN) are the substrate receptor and deneddylase of CRL4 E3 ligase, respectively. How they functionally interact remains unclear. Here, we uncover COP1–CSN antagonism during glucose-induced insulin secretion. Heterozygous Csn2WT/K70E mice with partially disrupted binding of IP6, a CSN cofactor, display congenital hyperinsulinism and insulin resistance. This is due to increased Cul4 neddylation, CRL4COP1 E3 assembly, and ubiquitylation of ETV5, an obesity-associated transcriptional suppressor of insulin secretion. Hyperglycemia reciprocally regulates CRL4-CSN versus CRL4COP1 assembly to promote ETV5 degradation. Excessive ETV5 degradation is a hallmark of Csn2WT/K70E, high-fat diet-treated, and ob/ob mice. The CRL neddylation inhibitor Pevonedistat/MLN4924 stabilizes ETV5 and remediates the hyperinsulinemia and obesity/diabetes phenotypes of these mice. These observations were extended to human islets and EndoC-βH1 cells. Thus, a CRL4COP1-ETV5 proteolytic checkpoint licensing GSIS is safeguarded by IP6-assisted CSN-COP1 competition. Deregulation of the IP6-CSN-CRL4COP1-ETV5 axis underlies hyperinsulinemia and can be intervened to reduce obesity and diabetic risk.

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