Silymarin prevents lipid accumulation in the liver of rats with type 2 diabetes via sirtuin1 and SREBP-1c

2018 ◽  
Vol 29 (3) ◽  
pp. 301-308 ◽  
Author(s):  
Nejat Kheiripour ◽  
Jamshid Karimi ◽  
Iraj Khodadadi ◽  
Heidar Tavilani ◽  
Mohammad Taghi Goodarzi ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Messenger Rna ◽  
Glycogen Content ◽  
Regulatory Element ◽  
Quantitative Polymerase Chain Reaction ◽  
Diabetic Rat ◽  
Model Assessment ◽  
Control Groups ◽  
Protein Carbonyl Content

Abstract Background: In this study, we have investigated whether silymarin intake influences lipid and glycogen content in conjunction with sirtuin1 (SIRT1) and sterol regulatory element-binding protein 1c (SREBP-1c) expressions in liver of type 2 diabetic rat. Methods: Thirty-six male Wistar rats were randomly divided into six groups: control groups (C) and diabetic groups (D); the control groups received 60 or 120 mg/kg silymarin (C+S60 or C+S120), and the diabetic groups received 60 or 120 mg/kg silymarin (D+S60 or D+S120) daily for 8 weeks. Serum biochemical parameters, as well as glycogen, lipid and oxidative stress biomarkers, in the liver tissue were measured by spectrophotometric methods. Additionally, SIRT1 and SREBP-1c messenger RNA (mRNA) expressions were evaluated by quantitative polymerase chain reaction. Results: Diabetes caused a significantly increased fasting blood sugar, homeostasis model assessment for insulin resistance, liver total cholesterol and triglyceride (TG) content, which were attenuated after the administration of silymarin. Dietary silymarin caused the improvement of lipid content in the liver of diabetic rats. Moreover, silymarin administration promoted SIRT1, suppressed SREBP-1c mRNA expression, reduced liver nitric oxide and protein carbonyl content, and increased liver glycogen, catalase and glutathione peroxidase activity. Furthermore, histopathological changes were improved in the treated groups. Conclusions: Silymarin administration considerably restored hepatic changes induced by streptozotocin and nicotinamide. The upregulation of SIRT1 mRNA expression by silymarin may be associated with decreased lipid, increased glycogen content and downregulation of the SREBP-1c gene in the liver.

scholarly journals Estrogen Metabolism in Abdominal Subcutaneous and Visceral Adipose Tissue in Postmenopausal Women

2017 ◽  
Vol 102 (12) ◽  
pp. 4588-4595 ◽  
Author(s):  
Natalia Hetemäki ◽  
Hanna Savolainen-Peltonen ◽  
Matti J Tikkanen ◽  
Feng Wang ◽  
Hanna Paatela ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mrna Expression ◽  
Postmenopausal Women ◽  
Messenger Rna ◽  
Metabolic Diseases ◽  
Quantitative Polymerase Chain Reaction ◽  
Subcutaneous Fat ◽  
Estrogen Metabolism ◽  
Serum Samples ◽  
Estrogen Exposure

Abstract Context In postmenopausal women, adipose tissue (AT) levels of estrogens exceed circulating concentrations. Although increased visceral AT after menopause is related to metabolic diseases, little is known about differences in estrogen metabolism between different AT depots. Objective We compared concentrations of and metabolic pathways producing estrone and estradiol in abdominal subcutaneous and visceral AT in postmenopausal women. Design, Setting, Patients, and Interventions AT and serum samples were obtained from 37 postmenopausal women undergoing surgery for nonmalignant gynecological reasons. Serum and AT estrone, estradiol, and serum estrone sulfate (E1S) concentrations were quantitated using liquid chromatography-tandem mass spectrometry. Activity of steroid sulfatase and reductive 17β-hydroxysteroid dehydrogenase enzymes was measured using radiolabeled precursors. Messenger RNA (mRNA) expression of estrogen-converting enzymes was analyzed by real-time reverse transcription quantitative polymerase chain reaction. Results Estrone concentration was higher in visceral than subcutaneous AT (median, 928 vs 706 pmol/kg; P = 0.002) and correlated positively with body mass index (r = 0.46; P = 0.011). Both AT depots hydrolyzed E1S to estrone, and visceral AT estrone and estradiol concentrations correlated positively with serum E1S. Compared with visceral AT, subcutaneous AT produced more estradiol from estrone (median rate of estradiol production, 1.02 vs 0.57 nmol/kg AT/h; P = 0.004). In visceral AT, the conversion of estrone to estradiol increased with waist circumference (r = 0.65; P = 0.022), and estradiol concentration correlated positively with mRNA expression of HSD17B7 (r = 0.76; P = 0.005). Conclusions Both estrone and estradiol production in visceral AT increased with adiposity, but estradiol was produced more effectively in subcutaneous fat. Both AT depots produced estrone from E1S. Increasing visceral adiposity could increase overall estrogen exposure in postmenopausal women.

scholarly journals Increase of E3 ubiquitin ligase NEDD4 expression leads to degradation of its target proteins PTEN/IGF1R during the formation of goose fatty liver

2020 ◽  
Vol 98 (9) ◽  
Author(s):  
Chunchi Yan ◽  
Minmeng Zhao ◽  
Shuo Li ◽  
Tongjun Liu ◽  
Cheng Xu ◽  
...  
Keyword(s):  
Fatty Liver ◽  
Mrna Expression ◽  
Messenger Rna ◽  
Quantitative Polymerase Chain Reaction ◽  
Normal Liver ◽  
Protective Mechanism ◽  
Nonalcoholic Fatty Liver ◽  
Target Proteins ◽  
Protein Levels ◽  
Gene 4

Abstract Goose fatty liver may have a unique protective mechanism as it does not show a pathological injury even in the case of severe steatosis. Although neural precursor cell-expressed developmentally downregulated gene 4 (NEDD4) participates in repair and regeneration of injured liver through its target proteins, its role in nonalcoholic fatty liver disease remains unknown. Using quantitative polymerase chain reaction (PCR) and immunoblot analyses, here, we found that the messenger RNA (mRNA) and protein expressions of NEDD4 were induced in goose fatty liver compared with normal liver. The mRNA expression of the gene of phosphate and tension homology deleted on chromosome ten (PTEN) and insulin-like growth factor 1 receptor (IGF1R) was also induced in goose fatty liver; however, their protein expression was or tended to be suppressed. Moreover, the co-immunoprecipitation analysis indicated that there was a physical association between NEDD4 and PTEN in goose liver, which was consistent with the ubiquitination of PTEN in goose fatty liver. Furthermore, NEDD4 overexpression in goose primary hepatocytes suppressed the PTEN and IGF1R protein levels without a significant effect on their mRNA expression. In conclusion, the increased expression of NEDD4 leads to the degradation of PTEN and IGF1R proteins through ubiquitination in goose fatty liver, suggesting that NEDD4 may protect goose fatty liver from severe steatosis-associated injury via its target proteins during the development of goose fatty liver.

scholarly journals Intermittent hypoxia training blunts cerebrocortical presenilin 1 overexpression and amyloid-β accumulation in ethanol-withdrawn rats

2017 ◽  
Vol 313 (1) ◽  
pp. R10-R18 ◽  
Author(s):  
Myoung-Gwi Ryou ◽  
Robert T. Mallet ◽  
Daniel B. Metzger ◽  
Marianna E. Jung
Keyword(s):  
Messenger Rna ◽  
Quantitative Polymerase Chain Reaction ◽  
Amyloid Β ◽  
Protein Carbonyl ◽  
Ethanol Withdrawal ◽  
Male Rats ◽  
Presenilin 1 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protein Carbonyl Content ◽  
Oxidative Protein Damage

Abrupt cessation of chronic alcohol consumption triggers signaling cascades that harm vulnerable brain regions and produce neurobehavioral deficits. We have demonstrated that a program of intermittent, normobaric hypoxia training (IHT) in rats prevents brain damage and neurobehavioral impairment resulting from abrupt ethanol withdrawal (EW). Moreover, EW induced expression of stress-activated protein kinase p38 and presenilin 1 (PS1), the catalytic subunit of γ-secretase that produces the neurotoxic amyloid-β (Aβ) peptides Aβ40 and Aβ42. We tested the hypotheses that 1) IHT limits EW-induced activation of the p38-PS1 axis, thereby attenuating γ-secretase activation and Aβ accumulation, and 2) EW disables heat shock protein 25 (HSP25), a p38 substrate, molecular chaperone, and antioxidant, and provokes protein carbonylation in a manner suppressed by IHT. Adult male rats completed two cycles of a 4-wk ethanol diet (6.5% wt/vol) and a 3-wk EW or an isocaloric, dextrin-based control diet. A 20-day IHT program (5–8 daily cycles of 5–10 min of 9.5–10% fractional inspired O2 + 4 min of 21% fractional inspired O2) was administered during the first EW phase. After the second EW phase, the brain was excised and the prefrontal cortex extracted. PS1, phosphorylated p38 (p-p38), and HSP25 were analyzed by immunoblot, PS1 messenger RNA by quantitative polymerase chain reaction, protein carbonyl content by spectrometry, and Aβ40 and Aβ42 contents by enzyme-linked immunosorbent assay. IHT attenuated the EW-associated increases in PS1, p-p38, Aβ40, Aβ42, and protein carbonyl contents, but not that of PS1 messenger RNA, while preserving functionally competent HSP25 dimers in EW rats. Collectively, these findings suggest that IHT may attenuate EW-induced γ-secretase overactivation by suppressing activation of the p38-PS1 axis and by preventing oxidative protein damage.

scholarly journals Cardiac Hepcidin Expression Associates with Injury Independent of Iron

2016 ◽  
Vol 44 (5) ◽  
pp. 368-378 ◽  
Author(s):  
G. Fenna van Breda ◽  
Lennart G. Bongartz ◽  
Wenqing Zhuang ◽  
Rachel P.L. van Swelm ◽  
Jeanne Pertijs ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Messenger Rna ◽  
Iron Homeostasis ◽  
Quantitative Polymerase Chain Reaction ◽  
Cardiac Injury ◽  
Tissue Growth ◽  
Hepcidin Expression ◽  
Sham Surgery ◽  
Hepcidin Gene

Background: Hepcidin regulates systemic iron homeostasis by downregulating the iron exporter ferroportin. Circulating hepcidin is mainly derived from the liver but hepcidin is also produced in the heart. We studied the differential and local regulation of hepcidin gene expression in response to myocardial infarction (MI) and/or chronic kidney disease (CKD). We hypothesized that cardiac hepcidin gene expression is induced by and regulated to severity of cardiac injury, either through direct (MI) or remote (CKD) stimuli, as well as through increased local iron content. Methods: Nine weeks after subtotal nephrectomy (SNX) or sham surgery (CON), rats were subjected to coronary ligation (CL) or sham surgery to realize 4 groups: CON, SNX, CL and SNX + CL. In week 16, the gene expression of hepcidin, iron and damage markers in cardiac and liver tissues was assessed by quantitative polymerase chain reaction and ferritin protein expression was studied by immunohistochemistry. Results: Cardiac hepcidin messenger RNA (mRNA) expression was increased 2-fold in CL (p = 0.03) and 3-fold in SNX (p = 0.01). Cardiac ferritin staining was not different among groups. Cardiac hepcidin mRNA expression correlated with mRNA expression levels of brain natriuretic peptide (β = 0.734, p < 0.001) and connective tissue growth factor (β = 0.431, p = 0.02). In contrast, liver hepcidin expression was unaffected by SNX and CL alone, while it had decreased 50% in SNX + CL (p < 0.05). Hepatic ferritin immunostaining was not different among groups. Conclusions: Our data indicate differences in hepcidin regulation in liver and heart and suggest a role for injury rather than iron as the driving force for cardiac hepcidin expression in renocardiac failure.

Melatonin and the heart circadian clock of euglycemic and type 2 diabetic male rats: a transcriptional evaluation

2019 ◽  
Vol 2 (3) ◽  
pp. 139-151
Author(s):  
Jose Sinesio-Jr ◽  
Paula Bargi-Souza ◽  
Raphael A Matos ◽  
Eduardo Almeida Leite ◽  
Daniella Carmo Buonfiglio ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Mrna Expression ◽  
Cardiac Dysfunction ◽  
Male Rats ◽  
Diabetic Rat ◽  
Dark Phase ◽  
Metabolic Dysfunction ◽  
Multiple Organs ◽  
Type 2 Diabetic

Diabetes increases risk of various comorbidities, including retinopathy, neuropathy, and cardiovascular disease, comprising both ischemic and non-ischemic cardiomyopathy. Cardiac dysfunction during diabetes is associated with perturbations at histologic, metabolic, biochemical and molecular levels. The circadian clock is misaligned in multiple organs during diabetes, including the heart. Such alterations in clock function have been postulated to play a causal role in cardiac dysfunction even though the mechanisms leading to circadian misalignment are currently unknown. Melatonin has been reported to alter heart circadian clock components and its circulating levels are decreased during diabetes. These observations led to the hypothesis that decreased melatonin levels during diabetes could be related to mismanagement of the heart clock. To evaluate this hypothesis, in the current study male Wistar and non-obese type 2 diabetic Goto-Kakizaki (GK) rats were given melatonin supplementation in their drinking water during the dark phase (for 12-wks), followed by assessment of clock component and the mRNA expression of the clock-controlled genes in the hearts of these animals. Melatonin supplementation significantly altered mRNA expression of targeted genes in both euglycemic and diabetic rat hearts. Collectively, under the condition of diabetes, the jeopardized pineal melatonin synthesis with misalignment of cardiac circadian clock components may likely mediate heart metabolic dysfunction, and/or even cause cardiovascular diseases.

scholarly journals THE PRO-INFLAMMATORY ROLE OF MICRORNA-29b IN DIABETIC NEPHROPATHY

2019 ◽  
pp. 210-213
Author(s):  
NAWAL KHINTEEL JABBAR ◽  
ANWARA JASIB THAABAN ALMZAIEL ◽  
FERDOUS ABASS JABER
Keyword(s):  
Diabetic Nephropathy ◽  
Healthy Subjects ◽  
Target Genes ◽  
Quantitative Polymerase Chain Reaction ◽  
B Cell Lymphoma ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Groups ◽  
And Control

Objectives: The objective of the study was to investigate the expression pattern of microRNA-29b (miRNA-29b) in patients with diabetic nephropathy (DN) compared to Type 2 diabetes mellitus (T2DM) and healthy subjects. Methods: Blood samples were obtained from 30 patients with DN, 30 patients with T2DM and 30 healthy subjects as controls. Serum reactive oxygen species (ROS) and interleukine-10 (IL-10) level were measured by enzyme-linked immunosorbent assay, and quantitative polymerase chain reaction was employed to screen the expression of serum miRNA-29b and anti-apoptotic B-cell lymphoma 2 (Bcl-2). Results: The results showed a significant increase in ROS levels (p<0.05) in DN group compared with T2DM and control groups. IL-10 levels were significantly increased compared to other groups (p<0.05). The gene expression of miRNA-29b was significantly increased with downregulation of Bcl-2 (p<0.05) in DN compared to T2DM and control groups (p<0.05). Conclusions: The study suggested that miRNA-29b expression is involved in the pathogenesis of DN. Hyperglycemia induced oxidative stress-mediated apoptosis, and an increase in expression of pro-inflammatory miRNA-29b exerts anti-protective effect by upregulating target genes related to inflammation and apoptosis, taken together, the results identify the regulatory role of miRNA-29b in DN.

scholarly journals The Effect of Combination of Quercetin And Glibenclamide on Myocardial Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Expression In Type 2 Diabetic Rat

2017 ◽  
Vol 16 (2) ◽  
pp. 302-306 ◽  
Author(s):  
Asri Hendrawati ◽  
Syaefudin Ali Akhmad ◽  
AH Sadewa ◽  
Tasmini
Keyword(s):  
Medical Science ◽  
Cellular Damage ◽  
Diabetic Rat ◽  
Control Group ◽  
Related Factor ◽  
Nuclear Factor ◽  
Control Groups ◽  
Nrf2 Expression ◽  
Type 2 Diabetic

Background. Diabetes mellitus (DM) is a metabolic disorder syndrome that marked by hyperglycemia. The main macrovascular complication is heart failure due to diabetic cardiomyopathy. Hyperglycemia can increase reactive oxygen species (ROS) and lipid peroxidation that induce cellular damage. Quercetin is an antioxidant that reduce hyperglycemia and ROS by modify the expression of nuclear factor erythroid 2-related factor 2 (Nrf 2).Objective. The aim of this research was to investigate the effect of combination of quercetin and glibenclamide on myocardial nuclear factor erythroid 2-related factor 2 (nrf 2) expression in type 2 diabetic rat compared with no combination.Methods. The rats were divided randomly into nine groups (each group consisted of four rats). The control group consist of a normal group that received placebo, DM control groups that received placebo and glibenclamide and intervention groups received quercetin 5, 20 and 80 mg/kgbw/day and combination of quercetin with 5 mg/kgbw/day of glibenclamide orally for a period of four weeks. The expression of myocardial Nrf 2 was measured by immunohistochemistry. Data was analyzed by ANOVA and p<0.05 was considered as significant. Results. Twenty and 80 mg/kgbw/day of quercetin with or without combination with glibenclamide orally for a period of four weeks increase myocardial Nrf2 expression higher than placebo (p<0.05). Eighty mg/kgbw/day of quercetin increase myocardial Nrf2 expression higher than 5 and 20 mg/kgbw/day (p<0.05).Conclusion. From this study it can be suggested that there are significant different in expression level of myocardial Nrf2 of type 2 DM after a combination of quercetin and glibenclamide, quercetin alone, glibenclamide alone and placebo.Bangladesh Journal of Medical Science Vol.16(2) 2017 p.302-306

Peripheral mononuclear TNF-α, visfatin, and resistin mRNA expression in overweight women with type 2 diabetes

2007 ◽  
Vol 2 (04) ◽  
Author(s):  
P Tsiotra ◽  
C Tsigos ◽  
E Yfanti ◽  
E Anastasiou ◽  
SA Raptis
Keyword(s):  
Type 2 Diabetes ◽  
Mrna Expression ◽  
Overweight Women ◽  
Tnf Α ◽  
Resistin Mrna

scholarly journals Ayurveda Body–Mind Constitutional Types and Role of Yoga Intervention Among Type 2 Diabetes Mellitus Population of Chandigarh and Panchkula Regions

2021 ◽  
pp. 097275312110000
Author(s):  
Madhava Sai Sivapuram ◽  
Vinod Srivastava ◽  
Navneet Kaur ◽  
Akshay Anand ◽  
Raghuram Nagarathna ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Lipid Profiles ◽  
Control Groups ◽  
Yoga Intervention ◽  
Positive Effects ◽  
Study Results ◽  
Significant Difference ◽  
And Control

Background: Type 2 diabetes needs a better understanding of etiological factors and management strategies based on lifestyle and constitutional factors, given its high association rate with many cardiovascular, neurological disorders, and COVID-19 infection. Purpose: The present study was undertaken to investigate the effect of Diabetes-specific integrated Yoga lifestyle Protocol (DYP) on glycemic control and lipid profiles of diabetic adults. Along with the DYP intervention, the individuals residing in Chandigarh and Panchkula union territories in the northern part of India were assessed for Ayurveda-based body–mind constitutional type. Ayurveda describes body–mind constitution as “ prakriti,” which has been discussed from two angles, namely physiological and psychological as body and mind are correlated. Methods: Cluster sampling of waitlist control study subjects was used as the sampling method for the study. A total of 1,215 registered subjects (81 diabetic) responded in randomly selected clusters in Chandigarh and Panchkula. Ayurveda physicians did Ayurveda body–mind constitutional assessment called prakriti assessment (physiological body–mind constitution assessment) in 35 participants (23 diabetic, 12 prediabetic) as a part of the study. Results: A group of 50 subjects was randomly selected for yoga intervention out of 81 diabetes mellitus adults, and 31 subjects were enrolled as waitlist controls. A significant decrease in the glycosylated hemoglobin levels from 8.49 ± 1.94% to 7.97 ± 2.20% in the intervention group was noticed. The lipid profiles of the DYP intervention and control groups were monitored. Three-month follow-up results of lipid profile diagnostic tests in intervention and control groups showed a significant difference between the two groups ( P < 0.05). Most diabetic and prediabetic individuals were found to have pitta dosha ( pitta controls all heat, metabolism, and transformation in the mind and body) as dominant constitution type. Conclusion: The study results demonstrated significant positive effects of yoga in diabetic individuals. This study has indicated the evidence for the safety and efficacy of the validated DYP for community-level interventions to prevent maladies like brain damage and stroke.

scholarly journals Oleuropein Ameliorates Advanced Stage of Type 2 Diabetes in db/db Mice by Regulating Gut Microbiota

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2131
Author(s):  
Shujuan Zheng ◽  
Yanan Wang ◽  
Jingjing Fang ◽  
Ruixuan Geng ◽  
Mengjie Li ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gut Microbiota ◽  
Relative Abundance ◽  
Fasting Blood Glucose ◽  
Therapeutic Effects ◽  
Model Assessment ◽  
Advanced Stage ◽  
Intestinal Microbes ◽  
Promising Therapeutic Approach

Previous studies have reported the therapeutic effects of oleuropein (OP) consumption on the early stage of type 2 diabetes. However, the efficacy of OP on the advanced stage of type 2 diabetes has not been investigated, and the relationship between OP and intestinal flora has not been studied. Therefore, in this study, to explore the relieving effects of OP intake on the advanced stage of type 2 diabetes and the regulatory effects of OP on intestinal microbes, diabetic db/db mice (17-week-old) were treated with OP at the dose of 200 mg/kg for 15 weeks. We found that OP has a significant effect in decreasing fasting blood glucose levels, improving glucose tolerance, lowering the homeostasis model assessment–insulin resistance index, restoring histopathological features of tissues, and promoting hepatic protein kinase B activation in db/db mice. Notably, OP modulates gut microbiota at phylum level, increases the relative abundance of Verrucomicrobia and Deferribacteres, and decreases the relative abundance of Bacteroidetes. OP treatment increases the relative abundance of Akkermansia, as well as decreases the relative abundance of Prevotella, Odoribacter, Ruminococcus, and Parabacteroides at genus level. In conclusion, OP may ameliorate the advanced stage of type 2 diabetes through modulating the composition and function of gut microbiota. Our findings provide a promising therapeutic approach for the treatment of advanced stage type 2 diabetes.

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