scholarly journals Adipokine Chemerin Stimulates Progression of Atherosclerosis in ApoE−/− Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Huadong Liu ◽  
Wei Xiong ◽  
Yu Luo ◽  
Hua Chen ◽  
Yaqiong He ◽  
...  
Keyword(s):  
P38 Mapk ◽  
High Fat Diet ◽  
Transforming Growth Factor ◽  
Elevated Serum ◽  
Serum Levels ◽  
Nuclear Antigen ◽  
High Fat ◽  
Aortic Plaque ◽  
Protein Levels ◽  
Progression Of Atherosclerosis

Background. Vascular remodeling is the most critical pathogenesis of atherosclerosis. Adipokine chemerin was known for its relationship with obesity as well as metabolism. Most recently, chemerin was found to play a crucial role in the pathologic process of cardiovascular diseases including coronary heart disease. In this study, we surveyed the role of chemerin in progression of atherosclerosis in ApoE−/− mice. Objective. To investigate the relationship between chemerin and progression of atherosclerosis in ApoE−/− mice and its mechanism. Methods. 8-week-old ApoE−/− mice were fed with high-fat diet to induce the atherosclerosis model. Adenoviruses were transfected for knockdown or overexpression of chemerin gene into aorta. Serums and aortic tissues of ApoE−/− mice were obtained after feeding high-fat diet for 16 weeks. HE staining and oil red staining were performed to evaluate aortic plaque. ELISA was performed to explore serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and transforming growth factor-β1 (TGF-β1). Real-time PCR and western blotting were carried out to investigate the mRNA and protein levels of chemerin, nuclear factor-κB p65 (NF-κBp65), proliferating cell nuclear antigen (PCNA), phosphorylated p38 mitogen-activated protein kinase (p-p38-MAPK), phosphorylated c-Jun N-terminal kinase (p-JNK), and phosphorylated extracellular signal regulated kinase 1/2 (p-ERK 1/2). Result. Aortic plaque formation was significantly induced by high-fat diet in ApoE−/− mice. Simultaneously, elevated serum levels of TNF-α and IL-1β and elevated mRNA and protein levels of chemerin, NF-κBp65, PCNA, p-p38-MAPK, p-JNK, and p-ERK 1/2 were found in ApoE−/− mice. After aortic chemerin gene was inhibited by adenovirus, aortic atherosclerosis induced by high-fat diet was significantly meliorated, serum levels of TNF-α and IL-1β decreased, mRNA and protein levels of NF-κBp65, PCNA, p-p38-MAPK, p-JNK, and p-ERK 1/2 decreased simultaneously. Conclusion. Our study revealed that chemerin stimulated the progression of atherosclerosis in ApoE−/− mice.

scholarly journals Mechanisms of Protective Effect of Ramulus Mori Polysaccharides on Renal Injury in High-Fat Diet/Streptozotocin-Induced Diabetic Rats

2015 ◽  
Vol 37 (6) ◽  
pp. 2125-2134 ◽  
Author(s):  
Xi Li ◽  
Ling Wang ◽  
Xingxin Gao ◽  
Guoping Li ◽  
Honghua Cao ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Transforming Growth Factor ◽  
Antioxidant Activities ◽  
Serum Levels ◽  
Diabetic Rats ◽  
Biochemical Changes ◽  
Ultrastructural Changes ◽  
High Fat ◽  
Protein Levels ◽  
Stage Renal Disease

Background: Diabetic nephropathy (DN) is the most important complication of diabetes and the most common cause of end-stage renal disease (ESRD). Aims: A recent study established that the Ramulus mori polysaccharides (RMP) exert antioxidant effects on DN in rats. Methods: The diabetic rats which induced by high-fat diet and streptozotocin injection were orally administered RMP by doses of 250, 500 and 1000 mg/kg daily for 8 weeks. The effects of RMP on hyperglycemia and other biochemical changes were examined in the sera and kidney tissues. Additionally, the pathological and ultrastructural changes and expressions of nuclear-factor kappa B (NF-κB) and transforming growth factor-ß1 (TGF-ß1) were assessed. Results: The results revealed that the serum levels of blood glucose, total cholesterol (TC) and triglycerides (TG) were significantly decreased by RMP. Furthermore, the blood urea nitrogen (BUN), serum creatinine (SCr) and 24-hour urine protein levels in the RMP-medicated rats were lower than those in untreated diabetic rats. Moreover, treatment of the DN rats with RMP normalized all biochemical changes, including the malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels in the serum and kidney tissues. In contrast, the protein expression levels of NF-κB and TGF-ß1, which were enhanced in the kidneys of DN rats, were reduced by RMP. Conclusion: These results suggest that RMP improving the renal function of diabeitc rats possibly via its ameliorating antioxidant activities.

scholarly journals Functional and Structural Changes in the Kidney in the Early Stages of Obesity

2001 ◽  
Vol 12 (6) ◽  
pp. 1211-1217
Author(s):  
JEFFREY R. HENEGAR ◽  
STEVEN A. BIGLER ◽  
LISA K. HENEGAR ◽  
SURESH C. TYAGI ◽  
JOHN E. HALL
Keyword(s):  
Arterial Pressure ◽  
High Fat Diet ◽  
Structural Changes ◽  
Transforming Growth Factor ◽  
Renal Plasma Flow ◽  
Basement Membranes ◽  
Nuclear Antigen ◽  
High Fat ◽  
Functional Changes ◽  
Early Stages

Abstract. The purpose of this study was to examine the histologic and functional changes that occur in the kidney in the early stages of obesity caused by a high-fat diet. Lean dogs (n = 8) were fed a standard kennel ration, and obese dogs (n = 8) were fed the standard kennel ration plus a supplement of cooked beef fat each day for 7 to 9 wk or 24 wk. Body weights were 58 ± 5% greater and kidney weights were 31 ± 7% greater in obese dogs, compared with the average values for lean dogs. Plasma renin activity and insulin concentrations were both 2.3-fold greater in obese dogs, compared with lean dogs. Obesity was associated with a mean arterial pressure increase of 12 ± 3 mmHg, a 38 ± 6% greater GFR, and a 61 ± 7% higher renal plasma flow, compared with lean dogs. The glomerular Bowman's space area was significantly greater (+41 ± 7%) in dogs fed the high-fat diet, compared with lean animals, mainly because of expansion of Bowman's capsule (+22 ± 7%). There was also increased mesangial matrix and thickening of the glomerular and tubular basement membranes and the number of dividing cells (proliferating cell nuclear antigen-stained) per glomerulus was 36 ± 8% greater in obese dogs, compared with lean dogs. There was also a trend for glomerular transforming growth factor-β1 expression, as estimated by semiquantitative immunohistochemical analysis, to be elevated with the high-fat diet. Therefore, a high-fat diet caused increased arterial pressure, hyperinsulinemia, activation of the renin-angiotensin system, glomerular hyperfiltration, and structural changes in the kidney that may be the precursors of more severe glomerular injury associated with prolonged obesity.

scholarly journals EX-527 Prevents the Progression of High-Fat Diet-Induced Hepatic Steatosis and Fibrosis by Upregulating SIRT4 in Zucker Rats

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1101 ◽  
Author(s):  
Amit Kundu ◽  
Prasanta Dey ◽  
Jae Hyeon Park ◽  
In Su Kim ◽  
Seung Jun Kwack ◽  
...  
Keyword(s):  
Hepatic Fibrosis ◽  
High Fat Diet ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Critical Role ◽  
Normal Subjects ◽  
Serum Levels ◽  
Zucker Rats ◽  
High Fat ◽  
Nonalcoholic Fatty Liver

Sirtuin (SIRT) is known to prevent nonalcoholic fatty liver disease (NAFLD); however, the role of SIRT4 in the progression of hepatic fibrosis remains unknown. We hypothesize that EX-527, a selective SIRT1 inhibitor, can inhibit the progression of high-fat diet (HFD)-induced hepatic fibrosis. We found that SIRT4 expression in the liver of NAFLD patients is significantly lower than that in normal subjects. In this study, EX-527 (5 µg/kg), administered to HFD rats twice a week for ten weeks, reduced the serum levels of triglyceride (TG), total cholesterol, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) and attenuated hepatic fibrosis evidenced by Masson’s trichrome and hepatic fat by oil red-O staining. EX-527 upregulated SIRT2, SIRT3, and SIRT4 expression in the liver of HFD fed rats but downregulated transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) expression. It decreased proinflammatory cytokine production and hydroxyproline levels in the serum and SMAD4 expression and restored apoptotic protein (Bcl-2, Bax, and cleaved caspase-3) expression. These data propose a critical role for the SIRT4/SMAD4 axis in hepatic fibrogenesis. SIRT4 upregulation has the potential to counter HFD-induced lipid accumulation, inflammation, and fibrogenesis. We demonstrate that EX-527 is a promising candidate in inhibiting the progression of HFD-induced liver fibrosis.

scholarly journals The Cytoskeletal Elements MAP2 and NF-L Show Substantial Alterations in Different Stroke Models While Elevated Serum Levels Highlight Especially MAP2 as a Sensitive Biomarker in Stroke Patients

2021 ◽  
Author(s):  
Bianca Mages ◽  
Thomas Fuhs ◽  
Susanne Aleithe ◽  
Alexandra Blietz ◽  
Constance Hobusch ◽  
...  
Keyword(s):  
Animal Models ◽  
Neuronal Damage ◽  
Degradation Products ◽  
Focal Cerebral Ischemia ◽  
Elevated Serum ◽  
Serum Levels ◽  
Ultrastructural Level ◽  
Stroke Patients ◽  
Protein Levels ◽  
Cytoskeletal Elements

AbstractIn the setting of ischemic stroke, the neurofilament subunit NF-L and the microtubule-associated protein MAP2 have proven to be exceptionally ischemia-sensitive elements of the neuronal cytoskeleton. Since alterations of the cytoskeleton have been linked to the transition from reversible to irreversible tissue damage, the present study investigates underlying time- and region-specific alterations of NF-L and MAP2 in different animal models of focal cerebral ischemia. Although NF-L is increasingly established as a clinical stroke biomarker, MAP2 serum measurements after stroke are still lacking. Therefore, the present study further compares serum levels of MAP2 with NF-L in stroke patients. In the applied animal models, MAP2-related immunofluorescence intensities were decreased in ischemic areas, whereas the abundance of NF-L degradation products accounted for an increase of NF-L-related immunofluorescence intensity. Accordingly, Western blot analyses of ischemic areas revealed decreased protein levels of both MAP2 and NF-L. The cytoskeletal alterations are further reflected at an ultrastructural level as indicated by a significant reduction of detectable neurofilaments in cortical axons of ischemia-affected areas. Moreover, atomic force microscopy measurements confirmed altered mechanical properties as indicated by a decreased elastic strength in ischemia-affected tissue. In addition to the results from the animal models, stroke patients exhibited significantly elevated serum levels of MAP2, which increased with infarct size, whereas serum levels of NF-L did not differ significantly. Thus, MAP2 appears to be a more sensitive stroke biomarker than NF-L, especially for early neuronal damage. This perspective is strengthened by the results from the animal models, showing MAP2-related alterations at earlier time points compared to NF-L. The profound ischemia-induced alterations further qualify both cytoskeletal elements as promising targets for neuroprotective therapies.

scholarly journals Maternal high-fat diet induces metabolic stress response disorders in offspring hypothalamus

2017 ◽  
Vol 59 (1) ◽  
pp. 81-92 ◽  
Author(s):  
Long The Nguyen ◽  
Sonia Saad ◽  
Yi Tan ◽  
Carol Pollock ◽  
Hui Chen
Keyword(s):  
Endoplasmic Reticulum ◽  
Body Weight ◽  
Er Stress ◽  
High Fat Diet ◽  
Maternal Obesity ◽  
Mrna Level ◽  
Metabolic Stress ◽  
High Fat ◽  
Chemical Chaperone ◽  
Protein Levels

Maternal obesity has been shown to increase the risk of obesity and related disorders in the offspring, which has been partially attributed to changes of appetite regulators in the offspring hypothalamus. On the other hand, endoplasmic reticulum (ER) stress and autophagy have been implicated in hypothalamic neuropeptide dysregulation, thus may also play important roles in such transgenerational effect. In this study, we show that offspring born to high-fat diet-fed dams showed significantly increased body weight and glucose intolerance, adiposity and plasma triglyceride level at weaning. Hypothalamic mRNA level of the orexigenic neuropeptide Y (NPY) was increased, while the levels of the anorexigenic pro-opiomelanocortin (POMC), NPY1 receptor (NPY1R) and melanocortin-4 receptor (MC4R) were significantly downregulated. In association, the expression of unfolded protein response (UPR) markers including glucose-regulated protein (GRP)94 and endoplasmic reticulum DNA J domain-containing protein (Erdj)4 was reduced. By contrast, protein levels of autophagy-related genes Atg5 and Atg7, as well as mitophagy marker Parkin, were slightly increased. The administration of 4-phenyl butyrate (PBA), a chemical chaperone of protein folding and UPR activator, in the offspring from postnatal day 4 significantly reduced their body weight, fat deposition, which were in association with increased activating transcription factor (ATF)4, immunoglobulin-binding protein (BiP) and Erdj4 mRNA as well as reduced Parkin, PTEN-induced putative kinase (PINK)1 and dynamin-related protein (Drp)1 protein expression levels. These results suggest that hypothalamic ER stress and mitophagy are among the regulatory factors of offspring metabolic changes due to maternal obesity.

scholarly journals Elevated Serum Transforming Growth Factor β1 Levels in Epstein-Barr Virus-Associated Diseases and Their Correlation with Virus-Specific Immunoglobulin A (IgA) and IgM

2000 ◽  
Vol 74 (5) ◽  
pp. 2443-2446 ◽  
Author(s):  
Jingwu Xu ◽  
Ali Ahmad ◽  
James F. Jones ◽  
Riccardo Dolcetti ◽  
Emanuela Vaccher ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epstein Barr Virus ◽  
Transforming Growth Factor ◽  
Immunoglobulin A ◽  
Elevated Serum ◽  
Transforming Growth Factor Β ◽  
Serum Levels ◽  
Barr Virus ◽  
Associated Diseases ◽  
Epstein Barr

ABSTRACT Transforming growth factor β (TGF-β) is an immunosuppressive cytokine which can induce immunoglobulin A (IgA) switch and Epstein-Barr virus (EBV) replication in latently infected cells. Here we report elevated serum levels of TGF-β in various EBV-associated diseases correlating positively with EBV-specific IgA titers and negatively with IgM titers, suggesting a role for this cytokine in the pathogenesis of these diseases.

scholarly journals Baicalin Attenuates High Fat Diet-Induced Obesity and Liver Dysfunction: Dose-Response and Potential Role of CaMKKβ/AMPK/ACC Pathway

2015 ◽  
Vol 35 (6) ◽  
pp. 2349-2359 ◽  
Author(s):  
Youli Xi ◽  
Miaozong Wu ◽  
Hongxia Li ◽  
Siqi Dong ◽  
Erfei Luo ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Fatty Liver ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Liver Steatosis ◽  
Serum Levels ◽  
Whole Body ◽  
Therapeutic Effects ◽  
High Fat ◽  
Dependent Protein

Background/Aims: Obesity-associated fatty liver disease affects millions of individuals. This study aimed to evaluate the therapeutic effects of baicalin to treat obesity and fatty liver in high fat diet-induced obese mice, and to study the potential molecular mechanisms. Methods: High fat diet-induced obese animals were treated with different doses of baicalin (100, 200 and 400 mg/kg/d). Whole body, fat pad and liver were weighed. Hyperlipidemia, liver steatosis, liver function, and hepatic Ca2+/CaM-dependent protein kinase kinase β (CaMKKβ) / AMP-activated protein kinase (AMPK) / acetyl-CoA carboxylase (ACC) were further evaluated. Results: Baicalin significantly decreased liver, epididymal fat and body weights in high fat diet-fed mice, which were associated with decreased serum levels of triglycerides, total cholesterol, LDL, alanine transaminase and aspartate transaminase, but increased serum HDL level. Pathological analysis revealed baicalin dose-dependently decreased the degree of hepatic steatosis, with predominantly diminished macrovesicular steatosis at lower dose but both macrovesicular and microvesicular steatoses at higher dose of baicalin. Baicalin dose-dependently inhibited hepatic CaMKKβ/AMPK/ACC pathway. Conclusion: These data suggest that baicalin up to 400 mg/kg/d is safe and able to decrease the degree of obesity and fatty liver diseases. Hepatic CaMKKβ/AMPK/ACC pathway may mediate the therapeutic effects of baicalin in high fat diet animal model.

FPS-ZM1 Alleviates Circulating Indices of Liver Injury in Diet-Induced Type 2 Diabetic Mice

2022 ◽  
Author(s):  
Somayeh Aslani ◽  
Saman Bahrambeigi ◽  
Davoud Sanajou
Keyword(s):  
Liver Injury ◽  
High Fat Diet ◽  
Lifestyle Modification ◽  
Serum Levels ◽  
Diabetic Mice ◽  
High Fat ◽  
Lifestyle Modifications ◽  
Gamma Glutamyl Transpeptidase ◽  
Alcoholic Fatty Liver

Despite dietary/lifestyle modifications as well as glycemic and lipid control, non-alcoholic fatty liver disease (NAFLD) imposes a considerable risk to the patients by advancing to non-alcoholic steatohepatitis (NASH). The present investigation aims to evaluate the protective potential of FPS-ZM1, a selective inhibitor for advanced glycation end products (RAGE), against circulating indices of liver injury in high fat diet-induced diabetic mice. FPS-ZM1 at 0.5. 1, and 2 mg/kg (orally) was administered for 2 months, starting 4 months after provision of the high-fat diet. Tests for glucose homeostasis, liver injury markers, and hepatic/plasma miR-21 expressions were performed. FPS-ZM1 attenuated diabetes-induced elevations in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamate dehydrogenase (GLD), and alpha glutathione-S-transferase (α-GST) as well as alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT). It also decreased diabetes-associated elevations in serum ferritin and plasma cytokeratin 18 fragments. Additionally, FPS-ZM1 down-regulated elevated expressions of miR-21 in the liver and plasma of diabetic mice. These findings highlight the benefits of FPS-ZM in alleviating liver injury in mice evoked by high-fat diet-induced type 2 diabetes and suggest FPS-ZM1 as a new potential adjunct to the conventional diet/lifestyle modification and glycemic control in diabetics.

Abstract 382: Anti-MAA Antibodies in Sprague Dawley Rats are Increased in Response to a High Fat Western Diet

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Michael J Duryee ◽  
Anand Dusad ◽  
Scott W Shurmur ◽  
Michael D Johnston ◽  
Robert P Garvin ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Normal Diet ◽  
Western Diet ◽  
Sprague Dawley ◽  
High Fat ◽  
Sprague Dawley Rats ◽  
Stable Plaque ◽  
Circulating Antibodies ◽  
Modified Proteins ◽  
Progression Of Atherosclerosis

Introduction Malondialdehyde/Acetaldehyde (MAA) modified proteins have been suggested to play a role in the development/progression of atherosclerosis. Circulating antibodies directed against these proteins have recently been shown to be associated with the severity of the disease. More specifically, the isotype of the antibody to MAA correlated with either an acute MI (IgG) or stable plaque formation (IgA) formation. MAA is thought to form as a result of the oxidation of fat(s) and thus the concentration and antibody response should reflect the amount of fat in the diet. Objective The purpose of this study was to evaluate the antibody responses to MAA modified proteins following immunization and high fat western diet feeding in rats. Methods Male Sprague Dawley rats were immunized with MAA-modified protein weekly for 5 weeks and then assayed for antibodies to these proteins. Animals were then separated into the following groups: chow sham, chow MAA immunized, high fat sham, and high fat MAA immunized. The high fat animals were fed a Western diet with 2-thiouracil for 12 weeks, bled every 3 weeks, and serum assayed for the presence of circulating MAA antibodies. Results Prior to feeding with high fat diet, rats immunized with MAA-modified protein had a significant increase (P<0.001) in serum antibodies directed against these modified proteins compared to controls (N of 4 per group). Following feeding of high fat diet antibody concentrations increased 6 fold in the high fat MAA immunized group compared to the chow MAA immunized group (P<0.05). Antibodies in the high fat sham and chow sham had only minimal increases in antibodies to these proteins. Conclusions These data demonstrate that following immunization with MAA-modified proteins, circulating antibodies are produced that increase following consumption of a high fat Western diet. It suggests that MAA-modified proteins are produced at low levels following normal diet, producing antibodies which act as a normal clearance method for altered protein. When high fat consumption increases these antibody levels are increased in response to the oxidative stress. Implications Use of these antibodies as a biomarker in the future may help predict the onset or progression of atherosclerosis.

scholarly journals Notoginsenoside R1 Facilitated Wound Healing in High-Fat Diet/Streptozotocin-Induced Diabetic Rats

2022 ◽  
Vol 2022 ◽  
pp. 1-15
Author(s):  
Guangzhao Cao ◽  
Changpei Xiang ◽  
Rui Zhou ◽  
Yi Zhang ◽  
He Xu ◽  
...  
Keyword(s):  
Wound Healing ◽  
High Fat Diet ◽  
Transforming Growth Factor ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Therapeutic Drug ◽  
High Morbidity ◽  
Diabetic Wound ◽  
High Fat ◽  
Diabetic Wound Healing ◽  
Matrix Metallopeptidase

Diabetic ulcers bring about high morbidity and mortality in patients and cause a great economic burden to society as a whole. Since existing treatments cannot fulfil patient requirements, it is urgent to find effective therapies. In this study, the wound healing effect of topical notoginsenoside R1 (NR1) treatment on diabetic full-thickness wounds in type II diabetes mellitus (T2DM) was induced by the combination of a high-fat diet and streptozotocin (STZ) injection. NR1 significantly increased the wound closure rate, enhanced extracellular matrix (ECM) secretion, promoted collagen growth, increased platelet endothelial cell adhesion molecule-1 (CD31) expression, and decreased cleaved caspase-3 expression. RNA-Seq analysis identified ECM remodeling and inflammation as critical biological processes and Timp1 and Mmp3 as important targets in NR1-mediated wound healing. Further experiments showed that NR1-treated wounds demonstrated higher expression of tissue inhibitor of metalloproteinase 1 (TIMP1) and transforming growth factor-β1 (TGFβ1) and lower expression of matrix metallopeptidase 9 (MMP9), matrix metallopeptidase 3 (MMP3), interleukin-1β (IL-1β), and interleukin-6 (IL-6) than diabetic wounds. These investigations promote the understanding of the mechanism of NR1-mediated diabetic wound healing and provide a promising therapeutic drug to enhance diabetic wound healing.

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