scholarly journals Effects of Secretome from Fat Tissues on Ion Currents of Cardiomyocyte Modulated by Sodium-Glucose Transporter 2 Inhibitor

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3606
Author(s):  
Shih-Jie Jhuo ◽  
I-Hsin Liu ◽  
Wei-Chung Tsai ◽  
Te-Wu Chou ◽  
Yi-Hsiung Lin ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Glucose Transporter ◽  
Study Groups ◽  
Sglt2 Inhibitors ◽  
Delayed Rectifier ◽  
High Fat ◽  
Pericardial Fat ◽  
The Metabolic Syndrome ◽  
Glucose Transporter 2 ◽  
Significant Difference

Sodium-glucose transporter 2 (SGLT2) inhibitors were shown to decrease mortality from cardiovascular diseases in the EMPA-REG trial. However, the effects of empagliflozin (EMPA) for cardiac arrhythmia are not yet clarified. A total of 20 C57BL/6J mice were divided into four groups: (1) The control group were fed standard chow, (2) the metabolic syndrome (MS) group were fed a high-fat diet, (3) the empagliflozin (EMPA) group were fed a high-fat diet and empagliflozin 10 mg/kg daily, and (4) the glibenclamide (GLI) group were fed a high-fat diet and glibenclamide 0.6 mg/kg daily. All mice were sacrificed after 16 weeks of feeding. H9c2 cells were treated with adipocytokines from the pericardial and peripheral fat from the study groups. The delayed-rectifier potassium current (IK) and L-type calcium channel current (ICa,L) were measured by the whole-cell patch clamp techniques. Adipocytokines from the peripheral and pericardial fat tissues of mice with MS could decrease the IK and increase the ICa,L of cardiomyocytes. After treating adipocytokines from pericardial fat, the IK in the EMPA and GLI groups were significantly higher than that in the MS group. The IK of the EMPA group was also significantly higher than the GLI group. The ICa,L of the EMPA and GLI groups were significantly decreased overload compared with that of the MS group. However, there was no significant difference of IK and ICa,L among study groups after treating adipocytokines from peripheral fat. Adipocytokines from pericardial fat but not peripheral fat tissues after EMPA therapy attenuated the effects of IK decreasing and ICa,L increasing in the MS cardiomyocytes, which may contribute to anti-arrhythmic mechanisms of sodium-glucose transporter 2 (SGLT2) inhibitors.

Comparative effects of telmisartan, sitagliptin and metformin alone or in combination on obesity, insulin resistance, and liver and pancreas remodelling in C57BL/6 mice fed on a very high-fat diet

2010 ◽  
Vol 119 (6) ◽  
pp. 239-250 ◽  
Author(s):  
Vanessa Souza-Mello ◽  
Bianca M. Gregório ◽  
Fernando S. Cardoso-de-Lemos ◽  
Laís de Carvalho ◽  
Márcia B. Aguila ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Glucose Transporter ◽  
Oral Glucose ◽  
Free Access ◽  
High Fat ◽  
The Metabolic Syndrome ◽  
Glucose Transporter 2 ◽  
Drug Treatments

The aim of the present study was to evaluate the effects of monotherapies and combinations of drugs on insulin sensitivity, adipose tissue morphology, and pancreatic and hepatic remodelling in C57BL/6 mice fed on a very HF (high-fat) diet. Male C57BL/6 mice were fed on an HF (60% lipids) diet or SC (standard chow; 10% lipids) diet for 10 weeks, after which time the following drug treatments began: HF-T (HF diet treated with telmisartan; 5.2 mg·kg−1 of body weight·day−1), HF-S (HF diet treated with sitagliptin; 1.08 g·kg−1 of body weight·day−1), HF-M (HF diet treated with metformin; 310.0 mg·kg−1 of body weight·day−1), HF-TM (HF diet treated with telmisartan+metformin), HF-TS (HF diet treated with telmisartan+sitagliptin) and HF-SM (HF diet treated with sitagliptin+metformin). Treated groups also had free access to the HF diet, and treatments lasted for 6 weeks. Morphometry, stereological tools, immunostaining, ELISA, Western blot analysis and electron microscopy were used. The HF diet yielded an overweight phenotype, an increase in oral glucose intolerance, hyperinsulinaemia, hypertrophied islets and adipocytes, stage 2 steatosis (>33%), and reduced liver PPAR-α (peroxisome-proliferator-activated receptor-α) and GLUT-2 (glucose transporter-2) levels, concomitant with enhanced SREBP-1 (sterol-regulatory-element-binding protein-1) expression (P<0.0001). Conversely, all drug treatments resulted in significant weight loss, a reversal of insulin resistance, islet and adipocyte hypertrophy, and alleviated hepatic steatosis. Only the HF-T and HF-TS groups had body weights similar to the SC group at the end of the experiment, and the latter treatment reversed hepatic steatosis. Increased PPAR-α immunostaining in parallel with higher GLUT-2 and reduced SREBP-1 expression may explain the favourable hepatic outcomes. Restoration of adipocyte size was consistent with higher adiponectin levels and lower TNF-α (tumour necrosis factor-α) levels (P<0.0001) in the drug-treated groups. In conclusion, all of the drug treatments were effective in controlling the metabolic syndrome. The best results were achieved using telmisartan and sitagliptin as monotherapies or as a dual treatment, combining partial PPAR-γ agonism and PPAR-α activation in the liver with extended incretin action.

scholarly journals SPARC is required for the maintenance of glucose homeostasis and insulin secretion in mice

2019 ◽  
Vol 133 (2) ◽  
pp. 351-365 ◽  
Author(s):  
Catalina Atorrasagasti ◽  
Agostina Onorato ◽  
María L. Gimeno ◽  
Luz Andreone ◽  
Mariana Garcia ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Glucose Homeostasis ◽  
High Fat Diet ◽  
Glucose Transporter ◽  
Cell Types ◽  
High Fat ◽  
Metabolic Complications ◽  
Glucose Transporter 2 ◽  
Diabetes In Mice ◽  
Key Factor

Abstract Obesity, metabolic syndrome, and type 2 diabetes, three strongly interrelated diseases, are associated to increased morbidity and mortality worldwide. The pathogenesis of obesity-associated disorders is still under study. Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycoprotein expressed in many cell types including adipocytes, parenchymal, and non-parenchymal hepatic cells and pancreatic cells. Studies have demonstrated that SPARC inhibits adipogenesis and promotes insulin resistance; in addition, circulating SPARC levels were positively correlated with body mass index in obese individuals. Therefore, SPARC is being proposed as a key factor in the pathogenesis of obesity-associated disorders. The aim of this study is to elucidate the role of SPARC in glucose homeostasis. We show here that SPARC null (SPARC−/−) mice displayed an abnormal insulin-regulated glucose metabolism. SPARC−/− mice presented an increased adipose tissue deposition and an impaired glucose homeostasis as animals aged. In addition, the absence of SPARC worsens high-fat diet-induced diabetes in mice. Interestingly, although SPARC−/− mice on high-fat diet were sensitive to insulin they showed an impaired insulin secretion capacity. Of note, the expression of glucose transporter 2 in islets of SPARC−/− mice was dramatically reduced. The present study provides the first evidence that deleted SPARC expression causes diabetes in mice. Thus, SPARC deficient mice constitute a valuable model for studies concerning obesity and its related metabolic complications, including diabetes.

scholarly journals Loss of Immunohistochemical Reactivity in Association With Handling-Induced Dark Neurons in Mouse Brains

2020 ◽  
Vol 48 (3) ◽  
pp. 437-445
Author(s):  
Virawudh Soontornniyomkij ◽  
Rachel C. Chang ◽  
Benchawanna Soontornniyomkij ◽  
Jan M. Schilling ◽  
Hemal H. Patel ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Hippocampal Formation ◽  
Control Diet ◽  
Study Groups ◽  
Inflammatory Factor ◽  
High Fat ◽  
Middle Aged ◽  
Dark Neurons ◽  
Dark Neuron ◽  
Significant Difference

The handling-induced dark neuron is a histological artifact observed in brain samples handled before fixation with aldehydes. To explore associations between dark neurons and immunohistochemical alterations in mouse brains, we examined protein products encoded by Cav3 (neuronal perikarya/neurites), Rbbp4 (neuronal nuclei), Gfap (astroglia), and Aif1 (microglia) genes in adjacent tissue sections. Here, dark neurons were incidental findings from our prior project, studying the effects of age and high-fat diet on metabolic homeostasis in male C57BL/6N mice. Available were brains from 4 study groups: middle-aged/control diet, middle-aged/high-fat diet, old/control diet, and old/high-fat diet. Young/control diet mice were used as baseline. The hemibrains were immersion-fixed with paraformaldehyde and paraffin-embedded. In the hippocampal formation, we found negative correlations between dark neuron hyperbasophilia and immunoreactivity for CAV3, RBBP4, and glial fibrillary acidic protein (GFAP) using quantitative image analysis. There was no significant difference in dark neuron hyperbasophilia or immunoreactivity for any protein examined among all groups. In contrast, in the hippocampal fimbria, old age seemed to be associated with higher immunoreactivity for GFAP and allograft inflammatory factor-1. Our findings suggest that loss of immunohistochemical reactivity for CAV3, RBBP4, and GFAP in the hippocampal formation is an artifact associated with the occurrence of dark neurons. The unawareness of dark neurons may lead to misinterpretation of immunohistochemical reactivity alterations.

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

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

<p align="justify"><strong>ABSTRACT</strong><strong></strong></p><p align="justify"><strong>Background</strong>: 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 (<em>Caulerpa racemosa</em>) 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 (<em>Rattus norvegicus</em>) fed with high fat diet.</p><p align="justify"><strong>Method</strong>:  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 15<sup>th</sup>-28<sup>th</sup> days. Then the blood LDL cholesterol level measured on the 29<sup>th</sup> day.</p><p align="justify"><strong>Result :</strong> 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).</p><p align="justify"><strong>Conclusion: </strong>high fat diet significantly increase blood LDL cholesterol level and sea grapes extract (<em>Caulerpa racemosa</em>) significantly decrease blood LDL cholesterol level.</p><p align="justify"> </p><p align="justify"><strong>Keywords :</strong>Sea grapes extract, LDL cholesterol, high fat diet</p>

Particular Matter of Motor Vehicle Exposure and High-Fat Diet Effects on Kidney Histopathology, Creatinine, and Malondialdehyde (MDA) Levels in Wistar Rats

2021 ◽  
Vol 5 (3) ◽  
pp. 124-128
Author(s):  
Rizka Veni ◽  
Awal Prasetyo ◽  
Muflihatul Muniroh
Keyword(s):  
High Fat Diet ◽  
Wistar Rats ◽  
Motor Vehicle ◽  
Histopathological Change ◽  
Normal Diet ◽  
Control Group ◽  
High Fat ◽  
Control Group Design ◽  
Treatment Groups ◽  
Significant Difference

This study aims to analyze the effect of combination of motor vehicle particular matter exposure and high-fat diet in kidney histopathology, creatinine levels, and MDA levels in Wistar rats. This study used a posttest-only control group design. Eighteen healthy male Wistar rats were divided into three groups. The intervention groups received motor vehicle fume exposure for 100 s with normal diet (X1) or high-fat diet (X2), and the control group received no exposure (C). Data analysis was processed with a SPSS 25.0 computer program by using the one-way ANOVA test followed by post hoc LSD. The degree of kidney histopathological damage showed significant differences between the X1 and X2 groups when compared with the control group (p < 0.05). The results of the creatinine level examination found a significant difference between the X2 and C groups (p < 0.05) and the treatment groups X1 and X2 (p < 0.05). The results of kidney MDA level examination showed a significant difference between the treatment groups (X1 and X2) and the control group (p < 0.05). The combination of particular matter of motor vehicle fumes exposure and high-fat diet could induce kidney damage through histopathological change and increased creatinine levels and kidney MDA levels in Wistar rats.

scholarly journals 7-Hydroxymatairesinol improves body weight, fat and sugar metabolism in C57BJ/6 mice on a high-fat diet

2018 ◽  
Vol 120 (7) ◽  
pp. 751-762 ◽  
Author(s):  
Giorgio Biasiotto ◽  
Isabella Zanella ◽  
Federica Predolini ◽  
Ivonne Archetti ◽  
Moris Cadei ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Body Weight ◽  
High Fat Diet ◽  
Sugar Metabolism ◽  
Lipid Uptake ◽  
High Fat ◽  
Total Extract ◽  
The Metabolic Syndrome ◽  
Metabolic Genes

Abstract7-Hydroxymatairesinol (7-HMR) is a plant lignan abundant in various concentrations in plant foods. The objective of this study was to test HMRLignan™, a purified form of 7-HMR, and the correspondingPicea abiesextract (total extractP. abies; TEP) as dietary supplements on a background of a high-fat diet (HFD)-induced metabolic syndrome in mice and in the 3T3-L1 adipogenesis model. Mice, 3 weeks old, were fed a HFD for 60 d. Subgroups were treated with 3 mg/kg body weight 7-HMR (HMRLignan™) or 10 mg/kg body weight TEP by oral administration. 7-HMR and TEP limited the increase in body weight (−11 and −13 %) and fat mass (−11 and −18 %) in the HFD-fed mice. Epididymal adipocytes were 19 and −12 % smaller and the liver was less steatotic (−62 and −65 %). Serum lipids decreased in TEP-treated mice (−11 % cholesterol, −23 % LDL and −15 % TAG) and sugar metabolism was ameliorated by both lignan preparations, as shown by a more than 70 % decrease in insulin secretion and insulin resistance. The expression of several metabolic genes was modulated by the HFD with an effect that was reversed by lignan. In 3T3-L1 cells, the 7-HMR metabolites enterolactone (ENL) and enterodiol (END) showed a 40 % inhibition of cell differentiation accompanied by the inhibited expression of the adipogenic genesPPARγ,C/EBPαandaP2. Furthermore, END and ENL caused a 10 % reduction in TAG uptake in HEPA 1–6 hepatoma cells. In conclusion, 7-HMR and TEP reduce metabolic imbalances typical of the metabolic syndrome and obesity in male mice, whereas their metabolites inhibit adipogenesis and lipid uptakein vitro.

scholarly journals Mouse Microglial Calcitonin Receptor Knockout Impairs Hypothalamic Amylin Neuronal pSTAT3 Signaling but Lacks Major Metabolic Consequences

Metabolites ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 51
Author(s):  
Bernd Coester ◽  
Thomas A. Lutz ◽  
Christelle Le Foll
Keyword(s):  
High Fat Diet ◽  
Energy Homeostasis ◽  
Arcuate Nucleus ◽  
Calcitonin Receptor ◽  
High Fat ◽  
Leptin Signaling ◽  
Physiological Relevance ◽  
Major Player ◽  
Significant Difference ◽  
Anorectic Effect

Amylin and leptin synergistically interact in the arcuate nucleus of the hypothalamus (ARC) to control energy homeostasis. Our previous rodent studies suggested that amylin-induced interleukin-6 release from hypothalamic microglia may modulate leptin signaling in agouti-related peptide expressing neurons. To confirm the physiological relevance of this finding, the calcitonin receptor (CTR) subunit of the amylin receptor was selectively depleted in microglia by crossing tamoxifen (Tx) inducible Cx3cr1-CreERT2 mice with CTR-floxed mice. Unexpectedly, male mice with CTR-depleted microglia (KO) gained the least amount of weight of all groups regardless of diet. However, after correcting for the tamoxifen effect, there was no significant difference for body weight, fat mass or lean mass between genotypes. No alteration in glucose tolerance or insulin release was detected. However, male KO mice had a reduced respiratory quotient suggesting a preference for fat as a fuel when fed a high fat diet. Importantly, amylin-induced pSTAT3 was decreased in the ARC of KO mice but this was not reflected in a reduced anorectic response. On the other hand, KO mice seemed to be less responsive to leptin’s anorectic effect while displaying similar ARC pSTAT3 as Tx-control mice. Together, these data suggest that microglial amylin signaling is not a major player in the control of energy homeostasis in mice.

Sodium-glucose transporter 2 inhibition and cardiovascular events in patients with diabetes: information from clinical trials and observational real-world data

2018 ◽  
Vol 132 (18) ◽  
pp. 2003-2012 ◽  
Author(s):  
Giulia Ferrannini ◽  
Lars Rydén
Keyword(s):  
Real World ◽  
Glucose Transporter ◽  
Sglt2 Inhibitors ◽  
European Medicines Agency ◽  
Real World Data ◽  
Glucose Transporter 2 ◽  
Patients With Diabetes ◽  
Cv Disease ◽  
Intervention Trials ◽  
Randomised Controlled

Cardiovascular (CV) disease (CVD) is the main cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Despite optimal glycaemic control, standard antihyperglycaemic therapy failed to impact CV events in intervention trials; therefore, the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) issued a guidance to the pharmaceutical industry to specifically assess the CV outcomes and safety of new glucose-lowering drugs. Amongst them, sodium-glucose transporter 2 (SGLT2) inhibitors proved to not only provide good tolerance, few adverse effects, and good glycometabolic control, but also striking reduction in the risk of CV events. In this review, data from the main randomised controlled trials are presented, including post-hoc analyses looking into several aspects of CV protection. Moreover, the main findings from observational real-world studies to date are described, overall reassuring as regards to CV safety and efficacy of SGLT2 inhibitors. Finally, several mechanisms which might contribute to the cardioprotective effect of SGLT2 inhibition are depicted, including findings from recent mechanistic studies.

Abstract 686: Intervention with Naringenin Enhances Weight Loss, Potentiates Improvements in Metabolic Dysregulation and Halts Progression of Atherosclerosis Induced by a High-Fat Diet in LDLr-/- Mice.

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Amy C Burke ◽  
Brian G Sutherland ◽  
Julia M Assini ◽  
Murray W Huff
Keyword(s):  
Insulin Resistance ◽  
Weight Loss ◽  
Plasma Glucose ◽  
High Fat Diet ◽  
Lesion Size ◽  
Chow Diet ◽  
High Fat ◽  
Metabolic Dysregulation ◽  
The Metabolic Syndrome ◽  
Progression Of Atherosclerosis

Previous studies demonstrate that the addition of naringenin, a grapefruit flavonoid, to a high-fat diet prevents the development of many disorders of the metabolic syndrome and atherosclerosis in Ldlr-/- mice. Furthermore, in intervention studies, the addition of naringenin to a high-fat, high cholesterol (HFHC) diet reversed pre-established obesity, hyperlipidemia, hepatic steatosis, insulin resistance and improved atherosclerotic lesion pathology, but not lesion size. In the present intervention study, we tested the hypothesis that addition of naringenin to a chow diet would further improve pre-established metabolic dysregulation and attenuate lesion development, compared to chow alone. Ldlr-/- mice were fed a HFHC diet for 12 weeks to induce metabolic dysregulation. Subsequently, mice received one of 3 diets for another 12 weeks: 1) continuation of the HFHC diet, 2) an isoflavone-free chow diet or 3) isoflavone-free chow with 3% naringenin. At 12 weeks, the HFHC diet induced significant weight gain and increased adiposity. Intervention with chow alone reduced the weight gained during induction by 22%, whereas the addition of naringenin to chow induced a weight loss of 71%. Specifically, the reduction in adiposity was 2.75-times greater in naringenin-treated mice, compared to chow alone. The HFHC diet increased VLDL cholesterol 20-fold and LDL cholesterol 5-fold, which were reduced by intervention with both chow (>60%) and chow supplemented with naringenin (>80%). The HFHC diet induced insulin resistance and glucose intolerance. Naringenin improved insulin tolerance (plasma glucose AUC -38%) and glucose tolerance (plasma glucose AUC -58%), which was accompanied by normalization of plasma insulin and glucose. HFHC-induction promoted the development of intermediate atherosclerotic lesions. Continuation of the HFHC diet doubled lesion size. Intervention with chow alone attenuated lesion size progression by 65%. The addition of naringenin to chow slowed lesion progression by 90%, resulting in smaller lesions compared to chow intervention alone (P=0.042). We conclude that intervention with naringenin-supplemented chow enhances weight loss, improves metabolic dysregulation and halts the progression of atherosclerosis.

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