scholarly journals The dietary antioxidant quercetin reduces hallmarks of bleomycin-induced lung fibrogenesis in mice

2020 ◽  
Author(s):  
Agnes Wilhelmina Boots ◽  
Carmen Veith ◽  
Catrin Albrecht ◽  
Roger Bartholome ◽  
Marie Jose Drittij ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Tissue ◽  
Plasma Levels ◽  
Control Diet ◽  
Redox Balance ◽  
Inflammatory Lesions ◽  
Beneficial Effects ◽  
Dietary Antioxidant ◽  
Pulmonary Damage ◽  
Deficient Mice

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic, lethal disease of which the etiology is still not fully understood. Current treatment comprises two FDA-approved drugs that can slow down yet not stop or reverse the disease. As IPF pathology is associated with an altered redox balance, adding a redox modulating component to current therapy might exert beneficial effects. Quercetin is a dietary antioxidant with strong redox modulating capacities that is suggested to exert part of its antioxidative effects via activation of the redox-sensitive transcription factor Nrf2 that regulates endogenous antioxidant levels. Therefore, the aim of the present study was to investigate if the dietary antioxidant quercetin can exert anti-fibrotic effects in a mouse model of bleomycin-induced pulmonary fibrogenesis through Nrf2-dependent restoration of redox imbalance. Methods Homozygous Nrf2 deficient mice and their wildtype littermates were fed a control diet without or with 800 mg quercetin per kg diet from 7 days prior to a single 1 µg/2µl per g BW bleomycin challenge until they were sacrificed 14 days afterwards. Lung tissue and plasma were collected to determine markers of fibrosis (expression of extracellular matrix genes and histopathology), inflammation (pulmonary gene expression and plasma levels of Tumor Necrosis Factor-α (TNFα) and Keratinocyte Chemoattrachtant (KC)), and redox balance (pulmonary gene expression of antioxidants and malondialdehyde-dG (MDA)- DNA adducts). Results Mice fed the enriched diet for 7 days prior to the bleomycin challenge had significantly enhanced plasma and pulmonary quercetin levels (11.08 ± 0.73 µM versus 7.05 ± 0.2 µM) combined with increased expression of Nrf2 and Nrf2-responsive genes compared to mice fed the control diet in lung tissue. Upon bleomycin treatment, quercetin-fed mice displayed reduced expression of collagen (COL1A2) and fibronectin (FN1) and a tendency of reduced inflammatory lesions (2.8 ± 0.7 versus 1.9 ± 0.8). These beneficial effects were accompanied by reduced pulmonary gene expression of TNFα and KC, but not their plasma levels, and enhanced Nrf2-induced pulmonary antioxidant defences. In Nrf2 deficient mice, no effect of the dietary antioxidant on either histology or inflammatory lesions was observed. Conclusion Quercetin exerts anti-fibrogenic and anti-inflammatory effects on bleomycin-induced pulmonary damage in mice possibly through modulation of the redox balance by inducing Nrf2. However, quercetin could not rescue the bleomycin-induced pulmonary damage indicating that quercetin alone cannot ameliorate the progression of IPF.

scholarly journals The dietary antioxidant quercetin reduces hallmarks of bleomycin-induced lung fibrogenesis in mice

2019 ◽  
Author(s):  
Agnes Wilhelmina Boots ◽  
Carmen Veith ◽  
Catrin Albrecht ◽  
Roger Bartholome ◽  
Marie Jose Drittij ◽  
...  
Keyword(s):  
Gene Expression ◽  
Plasma Levels ◽  
Control Diet ◽  
Redox Balance ◽  
Current Therapy ◽  
Inflammatory Lesions ◽  
Beneficial Effects ◽  
Dietary Antioxidant ◽  
Pulmonary Damage ◽  
Deficient Mice

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic, lethal disease of unknown etiology. Current treatment comprises two FDA-approved drugs that can slow down yet not stop or reverse the disease. As IPF pathology is associated with an altered redox balance, adding a redox modulating component to current therapy might exert beneficial effects. Quercetin is a dietary antioxidant with strong redox modulating capacities suggested to exert part of its antioxidative effects via activation of the redox-sensitive transcription factor Nrf2. Therefore, the aim of the present study was to investigate if quercetin can exert anti-fibrotic effects in a mouse model of bleomycin-induced pulmonary fibrogenesis through Nrf2-dependent restoration of redox imbalance. Methods Homozygous Nrf2 deficient mice and their wildtype littermates were fed a control diet without or with 800 mg/kg quercetin from 7 days prior to a single 1 µg/2µl per g BW bleomycin challenge until they were sacrificed 14 days afterwards. Lung tissue and plasma were collected to determine markers of fibrosis (expression of extracellular matrix genes and histopathology), inflammation (pulmonary gene expression and plasma levels of Tumor Necrosis Factor-α (TNFα) and Keratinocyte Chemoattrachtant (KC)), and redox balance (pulmonary gene expression of antioxidants and malondialdehyde-dG (MDA)- DNA adducts). Results Mice fed the enriched diet had significantly enhanced plasma and pulmonary quercetin levels (11.08 ± 0.73 µM versus 7.05 ± 0.2 µM) combined with increased pulmonary expression of Nrf2 and Nrf2-responsive genes compared to mice fed the control diet. Upon bleomycin treatment, quercetin-fed mice displayed reduced expression of collagen (COL1A2) and fibronectin (FN1) and a tendency of reduced inflammatory lesions (2.8 ± 0.7 versus 1.9 ± 0.8). These beneficial effects were accompanied by reduced pulmonary gene expression of TNFα and KC, but not their plasma levels, and enhanced Nrf2-induced pulmonary antioxidant defences. In Nrf2 deficient mice, no effect of the dietary antioxidant on either histology or inflammatory lesions was observed. Conclusion Quercetin exerts anti-fibrogenic and anti-inflammatory effects on bleomycin-induced pulmonary damage in mice possibly through modulation of the redox balance by inducing Nrf2. However, quercetin could not rescue the bleomycin-induced pulmonary damage indicating that quercetin alone cannot ameliorate the progression of IPF.

scholarly journals The dietary antioxidant quercetin reduces hallmarks of bleomycin-induced lung fibrogenesis in mice

2020 ◽  
Author(s):  
Agnes Wilhelmina Boots ◽  
Carmen Veith ◽  
Catrin Albrecht ◽  
Roger Bartholome ◽  
Marie Jose Drittij ◽  
...  
Keyword(s):  
Gene Expression ◽  
Plasma Levels ◽  
Control Diet ◽  
Redox Balance ◽  
Current Therapy ◽  
Inflammatory Lesions ◽  
Beneficial Effects ◽  
Dietary Antioxidant ◽  
Pulmonary Damage ◽  
Deficient Mice

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic, lethal disease of unknown etiology. Current treatment comprises two FDA-approved drugs that can slow down yet not stop or reverse the disease. As IPF pathology is associated with an altered redox balance, adding a redox modulating component to current therapy might exert beneficial effects. Quercetin is a dietary antioxidant with strong redox modulating capacities suggested to exert part of its antioxidative effects via activation of the redox-sensitive transcription factor Nrf2. Therefore, the aim of the present study was to investigate if quercetin can exert anti-fibrotic effects in a mouse model of bleomycin-induced pulmonary fibrogenesis through Nrf2-dependent restoration of redox imbalance. Methods Homozygous Nrf2 deficient mice and their wildtype littermates were fed a control diet without or with 800 mg/kg quercetin from 7 days prior to a single 1 µg/2µl per g BW bleomycin challenge until they were sacrificed 14 days afterwards. Lung tissue and plasma were collected to determine markers of fibrosis (expression of extracellular matrix genes and histopathology), inflammation (pulmonary gene expression and plasma levels of Tumor Necrosis Factor-α (TNFα) and Keratinocyte Chemoattrachtant (KC)), and redox balance (pulmonary gene expression of antioxidants and malondialdehyde-dG (MDA)- DNA adducts). Results Mice fed the enriched diet had significantly enhanced plasma and pulmonary quercetin levels (11.08 ± 0.73 µM versus 7.05 ± 0.2 µM) combined with increased pulmonary expression of Nrf2 and Nrf2-responsive genes compared to mice fed the control diet. Upon bleomycin treatment, quercetin-fed mice displayed reduced expression of collagen (COL1A2) and fibronectin (FN1) and a tendency of reduced inflammatory lesions (2.8 ± 0.7 versus 1.9 ± 0.8). These beneficial effects were accompanied by reduced pulmonary gene expression of TNFα and KC, but not their plasma levels, and enhanced Nrf2-induced pulmonary antioxidant defences. In Nrf2 deficient mice, no effect of the dietary antioxidant on either histology or inflammatory lesions was observed. Conclusion Quercetin exerts anti-fibrogenic and anti-inflammatory effects on bleomycin-induced pulmonary damage in mice possibly through modulation of the redox balance by inducing Nrf2. However, quercetin could not rescue the bleomycin-induced pulmonary damage indicating that quercetin alone cannot ameliorate the progression of IPF.

scholarly journals Eicosapentaenoic acid actions on adiposity and insulin resistance in control and high-fat-fed rats: role of apoptosis, adiponectin and tumour necrosis factor-α

2007 ◽  
Vol 97 (2) ◽  
pp. 389-398 ◽  
Author(s):  
Patricia Pérez-Matute ◽  
Nerea Pérez-Echarri ◽  
J. Alfredo Martínez ◽  
Amelia Marti ◽  
María J. Moreno-Aliaga
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Body Weight ◽  
Adipose Tissue ◽  
Weight Gain ◽  
Body Weight Gain ◽  
Control Diet ◽  
Cafeteria Diet ◽  
High Fat ◽  
Beneficial Effects

n-3 PUFA have shown potential anti-obesity and insulin-sensitising properties. However, the mechanisms involved are not clearly established. The aim of the present study was to assess the effects of EPA administration, one of the n-3 PUFA, on body-weight gain and adiposity in rats fed on a standard or a high-fat (cafeteria) diet. The actions on white adipose tissue lipolysis, apoptosis and on several genes related to obesity and insulin resistance were also studied. Control and cafeteria-induced overweight male Wistar rats were assigned into two subgroups, one of them daily received EPA ethyl ester (1 g/kg) for 5 weeks by oral administration. The high-fat diet induced a very significant increase in both body weight and fat mass. Rats fed with the cafeteria diet and orally treated with EPA showed a marginally lower body-weight gain (P = 0·09), a decrease in food intake (P < 0·01) and an increase in leptin production (P < 0·05). EPA administration reduced retroperitoneal adipose tissue weight (P < 0·05) which could be secondary to the inhibition of the adipogenic transcription factor PPARγ gene expression (P < 0·001), and also to the increase in apoptosis (P < 0·05) found in rats fed with a control diet. TNFα gene expression was significantly increased (P < 0·05) by the cafeteria diet, while EPA treatment was able to prevent (P < 0·01) the rise in this inflammatory cytokine. Adiposity-corrected adiponectin plasma levels were increased by EPA. These actions on both TNFα and adiponectin could explain the beneficial effects of EPA on insulin resistance induced by the cafeteria diet.

scholarly journals Changes in Liver Gene Expression and Plasma Concentration of Rbp4, Fetuin-A, and Fgf21 in Sprague-Dawley Rats Subjected to Different Dietary Interventions and Bariatric Surgery

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Dominika Stygar ◽  
Wojciech Pigłowski ◽  
Elżbieta Chełmecka ◽  
Bronisława Skrzep-Poloczek ◽  
Tomasz Sawczyn ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dietary Patterns ◽  
Plasma Levels ◽  
Control Diet ◽  
Retinol Binding Protein ◽  
Fibroblast Growth Factor 21 ◽  
Relative Gene Expression ◽  
Gene Expressions ◽  
Fetuin A ◽  
Relative Gene

Purpose. To study the effect of duodenal-jejunal omega switch (DJOS) in combination with different dietary patterns on the retinol-binding protein (RBP4), fetuin-A, and fibroblast growth factor 21 (FGF21) plasma levels and their hepatic gene expressions in rats. Methods. A high-fat diet (HF) was given to 28 rats and 28 more were fed with a control diet (CD) for 2 months. After that, half of each group underwent either DJOS or SHAM surgery. For the next 2 months, half of the animals in each operation group were kept on the same diet as before and half of them had the diet changed. After 16 weeks of the experiment RBP4, fetuin-A, and FGF21 plasma levels as well as liver Rbp4, Ahsg, and Fgf21 gene expressions were measured. Results. DJOS had a reductive impact on plasma levels of RBP4, fetuin-A, and FGF21 and Rbp4, Ahsg, and Fgf21 relative gene expression in the liver when compared to SHAM. The HF/HF group expressed significantly higher RBP4 and fetuin-A plasma levels in comparison to the control. The HF diet used before and/or after surgery led to upregulation of Rbp4, Ahsg, and Fgf21 relative gene expression. The lowest levels of analyzed parameters were observed in the CD/CD group. Conclusions. The efficiency of DJOS surgery, measured by hepatokines’ plasma levels and their gene expressions in the liver, depends on the type of diet applied before and after surgery. Manipulation of dietary patterns can lead to marked improvements in metabolic profile after DJOS surgery.

scholarly journals Dietary Purple Potato Supplementation Ameliorates Gut Inflammation and Associated Colitis

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 535-535
Author(s):  
Shima Bibi ◽  
Yansong Xue ◽  
Yang He ◽  
Min Du ◽  
Boon Chew ◽  
...  
Keyword(s):  
Control Diet ◽  
Goblet Cells ◽  
Protective Effects ◽  
Mice Model ◽  
Differentiation Markers ◽  
Beneficial Effects ◽  
Funding Sources ◽  
Epithelial Structure ◽  
Biochemical Analyses ◽  
Deficient Mice

Abstract Objectives The incidence of inflammatory bowel disease (IBD) is rapidly increasing worldwide. Patients with IBD experience increased susceptibility to colorectal cancer and are associated with morbidity and mortality. Diets are known factors associated with IBD. This study examined the beneficial effects of dietary purple potato against spontaneous colitis and improving gut microbiota in interleukin (IL)-10-deficient mice, a commonly used IBD mice model. Methods IL-10-deficient mice at 7-week-old were assigned to a standard rodent diet (CON) or a control diet supplemented with 10% purple potato (dry feed weight) for 11 weeks, when colonic tissues were collected for histological and biochemical analyses. Results Purple potato supplementation had no effect on feed intake and body weight in IL-10-deficient mice during the 11-week feeding trial. Purple potato supplementation improved the colitis symptom and the integrity of the colonic epithelial structure with reduced inflammation and pathological scores. Furthermore, the density of goblet cells and differentiation markers for goblet cells was enhanced due to PP supplementation. Conclusions Data collectively showed that dietary purple potato supplementation had protective effects against colitis onset in IL-10-deficient mice and improved gut epithelial structure, providing a promising dietary approach for the management and prevention of colitis. Funding Sources USDA-NIFA and Northwest Potato Research Consortium.

scholarly journals Effects of Bacillus subtilis WB60 and Lactococcus lactis on Growth, Immune Responses, Histology and Gene Expression in Nile Tilapia, Oreochromis niloticus

2020 ◽  
Vol 8 (1) ◽  
pp. 67 ◽  
Author(s):  
Seonghun Won ◽  
Ali Hamidoghli ◽  
Wonsuk Choi ◽  
Youngjin Park ◽  
Won Je Jang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bacillus Subtilis ◽  
Lactococcus Lactis ◽  
Nile Tilapia ◽  
Control Diet ◽  
Challenge Test ◽  
Myeloperoxidase Activity ◽  
Beneficial Effects ◽  
Tnf Α ◽  
Nile Tilapia Oreochromis Niloticus

An eight-week feeding trial was conducted to evaluate the effects of a basal control diet (CON), Bacillus subtilis at 107 (BS7) and at 108 CFU/g diet (BS8), Lactococcus lactis at 107 CFU/g (LL7) and at 108 CFU/g diet (LL8), and oxytetracycline (OTC) at 4 g/kg diet on Nile tilapia. Fish with initial body weight of 2.83 ± 0.05 g (mean ± SD) were fed two times a day. Weight gain, specific growth rate, feed efficiency, protein efficiency ratio and lysozyme activity of fish fed BS8, LL8 and LL7 diets were significantly higher than those of fish fed CON diet (p < 0.05). Superoxide dismutase and myeloperoxidase activity of fish fed BS8, LL8, BS7, LL7 and OTC diets were significantly higher than those of fish fed CON diet. Intestinal villi length and muscular layer thickness of fish fed BS8, LL8 and LL7 diets were significantly higher than those of fish fed CON and OTC diets. Also, heat shock protein 70 (HSP70), interleukin (IL-1β), interferon-gamma (IFN-γ) and tumour necrosis factor (TNF-α) gene expression of fish fed BS8 and LL8 diets were significantly higher than those of fish fed CON diet. After 13 days of challenge test, cumulative survival rate of fish fed BS8 and LL8 diets were significantly higher than those of fish fed CON, BS7 and OTC diets. Based on these results, B. subtilis and L. lactis at 108 (CFU/g) could replace antibiotics, and have beneficial effects on growth, immunity, histology, gene expression, and disease resistance in Nile tilapia.

scholarly journals Dietary supplementation with an extract of lycopene-rich tomatoes does not reduce atherosclerosis in Watanabe Heritable Hyperlipidemic rabbits

2007 ◽  
Vol 97 (1) ◽  
pp. 6-10 ◽  
Author(s):  
Hanne Frederiksen ◽  
Salka E. Rasmussen ◽  
Malene Schrøder ◽  
Anette Bysted ◽  
Jette Jakobsen ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Intervention Studies ◽  
Plasma Lipids ◽  
Control Diet ◽  
Dietary Supplementation ◽  
Plant Oils ◽  
Aortic Atherosclerosis ◽  
Total Plasma ◽  
Beneficial Effects ◽  
Tomato Extract

Tomatoes are rich in lycopene and other carotenoids which have shown beneficial effects on CVD in epidemiological and intervention studies. In the present study the effect of an extract of lycopene-rich tomatoes, Lyc-O-Mato® on atherosclerosis was studied in Watanabe Heritable Hyperlipidemic rabbits. The rabbits were fed a control diet, a control diet supplemented with the tomato extract or a control diet supplemented with a mixture of plant oils for 16 weeks. Lycopene was detected only in plasma of rabbits receiving tomato extract. The tomato extract had no effect on cholesterol and triacylglycerol levels measured in total plasma, lipoprotein fractions and on aortic atherosclerosis evaluated biochemically and by microscopy. Oxidation of lipids in unfractionated plasma also was unaffected by the intake of tomato extract. In conclusion, the tomato extract increased plasma levels of lycopene in rabbits, but had no effect on hypercholesterolaemia, oxidation of plasma lipids or aortic atherosclerosis.

P6274Role of the nicotinamide riboside kinase 2 in NAD metabolism in the heart in basal and pathological condition

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
R Deloux ◽  
C Tannous ◽  
A Karoui ◽  
N Mougenot ◽  
Z Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cardiac Function ◽  
Pathological Condition ◽  
Control Diet ◽  
Functional Improvement ◽  
Wild Type ◽  
Vitamin B3 ◽  
Nad Metabolism ◽  
Nicotinamide Riboside ◽  
Beneficial Effects

Abstract Background NAD is a major coenzyme in energy metabolism and a substrate for SIRT1 and PARP1 enzymes involved in the response to energy and oxidative stress. We have shown the beneficial effects of nicotinamide riboside (NR), a new type of vitamin B3, on cardiac function and remodelling in a mouse model of dilated cardiomyopathy (DCM) triggered by deletion of the SRF transcription factor in the heart (Srf-HKO) (1). This functional improvement correlated with protection of NAD metabolism and a robust increase in cardiac expression of the Nicotinamide Riboside Kinase 2 (NMRK2) that phosphorylates NR to generate nicotinamide mononucleotide (NMN), an immediate precursor of NAD. Purpose We aim to understand the role of the NMRK2-mediated NAD biosynthetic pathway in the heart at baseline and in the DCM context. Methods We generated Nmrk2-KO mice that we bred with Srf-HKO to generate double KO mice (db-KO). We analysed cardiac function and remodelling by echocardiography and quantified myocardial NAD levels at baseline and following NR supplementation in food. Results Nmrk2KO mice developed a progressive eccentric remodelling of LV and decline in EF with aging. At 24-mo, we observed a reduction of myocardial NAD levels (−40% compared to wild type, p<0.05) and of LVEF (61%, SD 6.3% in Nmrk2-KO vs 78%, SD 1.5% in WT, p<0.05). To assess the contribution of cardiac Nmrk2 induction to NR response in DCM, we compared SrfH-KO and db-KO mice fed with control diet (CD) or NR supplemented diet for 40 days starting at young age (2-mo). NR reduced the extent of LV eccentric remodelling and drop in EF as well as the thinning of the LV posterior wall in both genotypes (2-way ANOVA, diet effect, p<0.01). Myocardial NAD levels were more reduced in db-KO mice under CD diet (−22% compared to control mice, p<0.05) than in Srf-HKO mice (−11%, non-significant), when we previously showed a 25% drop in myocardial NAD in aged SrfHKO mice (1). NR partially preserved cardiac NAD pool in db-KOmice (−10% compared to controls, non-significant). Parallel pathways for NMN synthesis were studied. Nampt gene expression was significantly repressed in db-KO mice fed with CD or NR diet compared to control mice (−50% in average, p<0.01), when there was only a trend toward lower expression in SrfHKO mice (−40% in average, p>0.05). Nmrk1 gene expression trended to increase in all groups compared to wild-type control mice. Conclusion We show that NMRK2 pathway plays a role in the maintenance of basal cardiac function and NAD levels when relying on the endogenous myocardial NR pool. In contrast, the beneficial effect of a therapeutic dose of NR is not affected by the lack of NMRK2 suggesting compensation by NMRK1 in the heart and/or that NR beneficial effects on cardiac function could be mediated through its action on systemic metabolism. Aging appears as an aggravating factor for the loss of myocardial NAD coenzyme in DCM. Acknowledgement/Funding Agence Nationale pour la Recherche, Fondation de France

scholarly journals Interaction of clozapine with metformin in a schizophrenia rat model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
G. Horvath ◽  
G. Kis ◽  
G. Kekesi ◽  
A. Büki ◽  
L. G. Adlan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cognitive Function ◽  
Negative Symptoms ◽  
Antipsychotic Drugs ◽  
D1 Receptor ◽  
Antidiabetic Drug ◽  
Beneficial Effects ◽  
Adjuvant Therapies ◽  
Behavioral Parameters ◽  
The Brain

AbstractThe low efficacy of antipsychotic drugs (e.g., clozapine) for negative symptoms and cognitive impairment has led to the introduction of adjuvant therapies. Because previous data suggest the procognitive potential of the antidiabetic drug metformin, this study aimed to assess the effects of chronic clozapine and metformin oral administration (alone and in combination) on locomotor and exploratory activities and cognitive function in a reward-based test in control and a schizophrenia-like animal model (Wisket rats). As impaired dopamine D1 receptor (D1R) function might play a role in the cognitive dysfunctions observed in patients with schizophrenia, the second goal of this study was to determine the brain-region-specific D1R-mediated signaling, ligand binding, and mRNA expression. None of the treatments affected the behavior of the control animals significantly; however, the combination treatment enhanced D1R binding and activation in the cerebral cortex. The Wisket rats exhibited impaired motivation, attention, and cognitive function, as well as a lower level of cortical D1R binding, signaling, and gene expression. Clozapine caused further deterioration of the behavioral parameters, without a significant effect on the D1R system. Metformin blunted the clozapine-induced impairments, and, similarly to that observed in the control animals, increased the functional activity of D1R. This study highlights the beneficial effects of metformin (at the behavioral and cellular levels) in blunting clozapine-induced adverse effects.

scholarly journals Insulin treatment improves liver histopathology and decreases expression of inflammatory and fibrogenic genes in a hyperglycemic, dyslipidemic hamster model of NAFLD

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Victoria Svop Jensen ◽  
Christian Fledelius ◽  
Christina Zachodnik ◽  
Jesper Damgaard ◽  
Helle Nygaard ◽  
...  
Keyword(s):  
Cell Activation ◽  
Insulin Treatment ◽  
Stellate Cell ◽  
Control Diet ◽  
Diabetic Patients ◽  
Liver Pathology ◽  
Hamster Model ◽  
Alcoholic Fatty Liver ◽  
Beneficial Effects ◽  
Liver Histopathology

Abstract Background Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are highly prevalent comorbidities in patients with Type 2 diabetes. While many of these patients eventually will need treatment with insulin, little is known about the effects of insulin treatment on histopathological parameters and hepatic gene expression in diabetic patients with co-existing NAFLD and NASH. To investigate this further, we evaluated the effects of insulin treatment in NASH diet-fed hamsters with streptozotocin (STZ) -induced hyperglycemia. Methods Forty male Syrian hamsters were randomized into four groups (n = 10/group) receiving either a NASH-inducing (high fat, fructose and cholesterol) or control diet (CTRL) for four weeks, after which they were treated with STZ or sham-injected and from week five treated with either vehicle (CTRL, NASH, NASH-STZ) or human insulin (NASH-STZ-HI) for four weeks by continuous s.c. infusion via osmotic minipumps. Results NASH-STZ hamsters displayed pronounced hyperglycemia, dyslipidemia and more severe liver pathology compared to both CTRL and NASH groups. Insulin treatment attenuated dyslipidemia in NASH-STZ-HI hamsters and liver pathology was considerably improved compared to the NASH-STZ group, with prevention/reversal of hepatic steatosis, hepatic inflammation and stellate cell activation. In addition, expression of inflammatory and fibrotic genes was decreased compared to the NASH-STZ group. Conclusions These results suggest that hyperglycemia is important for development of inflammation and profibrotic processes in the liver, and that insulin administration has beneficial effects on liver pathology and expression of genes related to inflammation and fibrosis in a hyperglycemic, dyslipidemic hamster model of NAFLD.

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