Nobiletin ameliorates high-fat diet-induced vascular and renal changes by reducing inflammation with modulating AdipoR1 and TGF-β1 expression in rats

Life Sciences ◽  
2020 ◽  
Vol 260 ◽  
pp. 118398
Author(s):  
Sarawoot Bunbupha ◽  
Kwanjit Apaijit ◽  
Putcharawipa Maneesai ◽  
Patoomporn Prasarttong ◽  
Poungrat Pakdeechote
Keyword(s):  
High Fat Diet ◽  
High Fat ◽  
Renal Changes ◽  
Tgf Β1

Salvianolic Acid A Prevents the Pathological Progression of Hepatic Fibrosis in High-Fat Diet-Fed and Streptozotocin-Induced Diabetic Rats

2014 ◽  
Vol 42 (05) ◽  
pp. 1183-1198 ◽  
Author(s):  
Guifen Qiang ◽  
Xiuying Yang ◽  
Qi Xuan ◽  
Lili Shi ◽  
Hengai Zhang ◽  
...  
Keyword(s):  
Hepatic Fibrosis ◽  
High Fat Diet ◽  
Diabetic Rats ◽  
Type I ◽  
High Fat ◽  
Salvianolic Acid ◽  
Salvianolic Acid A ◽  
Underlying Mechanisms ◽  
Tgf Β1

Type 2 diabetes patients have an increased risk of developing hepatic fibrosis. Salvianolic acid A (SalA) has been reported to be a strong polyphenolic anti-oxidant and free radical scavenger. The aim of the present study was to evaluate the effect of SalA on the pathological progression of hepatic fibrosis in high-fat diet (HFD)-fed and streptozotocin (STZ)-induced diabetic rats and to clarify the underlying mechanisms. Type 2 diabetic animal model with hepatic fibrosis was developed by a high-sucrose, HFD and low-dose STZ injection (i.p.). Diabetic rats were randomly divided into SalA group (0.3 mg/kg/day) and diabetic control groups fed with a HFD. After administration for four months, SalA reversed the hyperlipidemia and reduced hepatic triglyceride (TG). Hematoxylin–Eosin (HE) and Picro acid-Sirius red staining results indicated that SalA significantly alleviated the lesions of hepatic steatosis and fibrosis, with the reduction of type I and III collagens. The expression of α-smooth-muscle-actin (α-SMA) and transforming growth factor β1 (TGF-β1) in the liver were markedly down-regulated by SalA treatment. TUNEL staining showed that SalA reduced apoptosis in hepatocytes. In addition, SalA improved hepatic mitochondrial respiratory function in diabetic rats. Taken together, these findings demonstrated that SalA could prevent the pathological progression of hepatic fibrosis in HFD-fed and STZ-induced diabetic rats. The underlying mechanisms may be involved in reducing oxidative stress, suppressing α-SMA and TGF-β1 expression, as well as exerting anti-apoptotic and mitochondria-protective effects.

scholarly journals Sex-dependent differences in the adverse renal changes induced by an early in life exposure to a high-fat diet

2019 ◽  
Vol 316 (2) ◽  
pp. F332-F340 ◽  
Author(s):  
Juan M. Moreno ◽  
Antonio Tapia ◽  
Carlos M. Martinez ◽  
Virginia Reverte ◽  
Lidia Oltra ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Arterial Pressure ◽  
High Fat Diet ◽  
Female Rats ◽  
Fat Intake ◽  
Early Exposure ◽  
Sprague Dawley ◽  
High Fat ◽  
Renal Changes ◽  
Renal Vascular

This study examines whether the intake of a high-fat diet very early in life leads to changes in arterial pressure and renal function and evaluates whether the mechanisms involved in these changes are sex-dependent. Experiments were performed in male and female Sprague-Dawley rats fed a normal or high-fat diet from weaning to 4 mo of age. This exposure to a high-fat diet lead to an angiotensin II-dependent elevation in arterial pressure and to significant increments in fat abdominal volume and plasma leptin that were similar in both sexes. In addition, the angiotensin II-induced increment in renal vascular resistance was greater ( P < 0.05) in male (106 ± 14%) and female (97 ± 15%) rats fed a high-fat diet than in rats fed a normal-fat diet (51 ± 8%). However, the high-fat intake during early life induced increments in albuminuria, interleukin-6, and infiltration of CD3 lymphocytes in the renal parenchyma that were greater ( P < 0.05) in male than in female rats. Other sex-dependent differences in response to high-fat intake were that adiponectin levels only decreased in females (21%, P < 0.05), and renal NF-κB expression only increased in males (31%, P < 0.05). In summary, the early exposure to a high-fat diet leads to angiotensin II-dependent arterial pressure elevations and to increments in abdominal fat and in the renal sensitivity to angiotensin II that are similar in both sexes. However, the mechanisms involved in the renal changes associated with early exposure to a high-fat diet are different in males and females.

scholarly journals High-fat diet causes increased serum insulin and glucose which synergistically lead to renal tubular lipid deposition and extracellular matrix accumulation

2011 ◽  
Vol 107 (1) ◽  
pp. 74-85 ◽  
Author(s):  
Jun Hao ◽  
Shu-xia Liu ◽  
Song Zhao ◽  
Qing-juan Liu ◽  
Wei Liu ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Extracellular Matrix ◽  
Lipid Droplet ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Serum Insulin ◽  
High Fat ◽  
Renal Tubular ◽  
Matrix Accumulation ◽  
Tgf Β1

Renal tubular lipid accumulation is associated with renal injury in the metabolic syndrome, but its mechanisms are not fully elucidated. The purpose of the present study was to investigate the exact mechanism of renal tubular lipid accumulation in the diet-induced metabolic syndrome. The in vivo experiments showed that a high-fat diet induced hyperglycaemia, hyperinsulinaemia and hypertriacylglycerolaemia, subsequent increases in sterol regulatory element binding protein-1 (SREBP-1) and transforming growth factor-β1 (TGF-β1), lipid droplet deposit in renal tubular cells and interstitial extracellular matrix accumulation in Wistar rats. A human renal proximal tubular epithelial cell line (HKC) was used to determine the direct role of insulin, and the results revealed that insulin induced SREBP-1, fatty acid synthase (FASN), TGF-β1 expressions, lipid droplet and extracellular matrix deposits. Knockdown of SREBP-1 by RNA interference technology significantly inhibited FASN, TGF-β1 up-regulation, lipid and extracellular matrix accumulation caused by insulin. In addition, we found that insulin and high glucose could synergistically increase SREBP-1, FASN, TGF-β1 and fibronectin expressions in HKC cells. These results indicate that high-fat diet-induced increased serum insulin and glucose synergistically cause renal tubular lipid deposit and extracellular matrix accumulation via the SREBP-1 pathway.

Gender differences in the renal changes induced by a prolonged high-fat diet in rats with altered renal development

2021 ◽  
Author(s):  
Juan M. Moreno ◽  
Carlos M. Martinez ◽  
Carlos de Jodar ◽  
Virginia Reverte ◽  
Antonio Bernabé ◽  
...  
Keyword(s):  
Gender Differences ◽  
High Fat Diet ◽  
Renal Development ◽  
High Fat ◽  
Renal Changes

scholarly journals Insulin resistance mediates high-fat diet-induced pulmonary fibrosis and airway hyperresponsiveness through the TGF-β1 pathway

2019 ◽  
Vol 51 (5) ◽  
pp. 1-12 ◽  
Author(s):  
Yoon Hee Park ◽  
Eun Yi Oh ◽  
Heejae Han ◽  
Misuk Yang ◽  
Hye Jung Park ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Pulmonary Fibrosis ◽  
High Fat Diet ◽  
Airway Hyperresponsiveness ◽  
High Fat ◽  
Tgf Β1

scholarly journals Ruanmailing Oral Liquid Inhibit Atherosclerosis in ApoE-/- Mice by Regulation of TGF-β1/SMAD4 Signaling Pathway

2021 ◽  
Author(s):  
Tianmin Wu ◽  
Xuanbin Huang ◽  
Jinshui Chen ◽  
Wenjuan Xue ◽  
Liufang Fan ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Thoracic Aorta ◽  
High Fat Diet ◽  
Pathological Examination ◽  
Enzyme Linked Immunosorbent Assay ◽  
High Dose ◽  
Model Group ◽  
High Fat ◽  
Oral Liquid ◽  
Tgf Β1

Abstract BackgroundTo investigate the effect of Ruanmailing oral liquid on atherosclerosis and TGF-β1/SMAD4 signaling pathway in ApoE knockout mice induced by high-fat diet. MethodsForty ApoE-/- mice were randomly divided into 5 groups, and mice fed with standard diets were the control group. ApoE-/- mice high-fat diet induced atherosclerotic phenotype. After grouping and treatment, they were divided into high-fat feeding model group, low-dose and high-dose of Ruanmailing groups (1.75, 4.55 ml/kg/d), Lipitor Group (3.0 mg/kg/d). After 12 weeks of administration, blood was collected from the mice orbit to determine the levels of TC, TG, LDL-C, and HDL-C, and the pathological changes of thoracic aorta atherosclerosis were observed. Enzyme-linked immunosorbent assay (ELISA) was used to detect the concentration of serum TGF-β1, and RT-PCR and Western Blot were used to detect the expression of SMAD4 and GATA2 in the thoracic aorta of ApoE-/- mice in each group. ResultsCompared with the high-fat model group, the serum lipids level of each administration group were reduced (P<0.01 or P<0.05), and the ratio of plaque area to luminal area (W/L) was significantly reduced (P<0.05), and pathological examination indicated atherosclerotic lesions in thoracic aorta of ApoE-/- mice were alleviated, and the high-dose Ruanmailing group had the most significant anti-atherosclerotic effect. ConclusionsRuanmailing oral liquid has an anti-atherosclerotic effect, and its mechanism may be related to the intervention of GATA2 in the TGF-β1/SMAD4 signaling pathway to reduce the differentiation and proliferation of arterial smooth muscle cells.

scholarly journals Epicardial adipose tissie-derived leptin induce MMPs/TIMPs imbalance and promotes myocardial remodeling in high fat diet-induced obese rats

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
G Tian ◽  
L Liu ◽  
C D Luo ◽  
M Li ◽  
L F Cao ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
High Fat Diet ◽  
Type I Collagen ◽  
Nuclear Translocation ◽  
Cardiac Fibroblasts ◽  
Type I ◽  
Myocardial Remodeling ◽  
High Fat ◽  
Obese Rats ◽  
Tgf Β1

Abstract Background and aims Epicardial adipose tissue (EAT)-derived leptin contributes to myocardial remodeling in metabolic syndrome. However, the precise mechanisms remain to be determined. The present study was designed to elucidate the adverse effects of EAT-derived leptin on obesity-related myocardial remodeling. Methods and results Eight-week-old male Wistar rats were divided into two groups that received either a normal diet (control, n=10) or a high-fat diet (obese, n=10) for 12 weeks. Obese rats exhibited abnormal myocardial structure, diastolic dysfunction and abundant collagen deposition. Local leptin expression in obese rats EAT upregulated along with adipocyte hypertrophy, accompanied by renin-angiotensin-aldosterone system (RAAS) activation and increased oxidative stress level. Leptin receptor (ObR) and angiotensin II type 1 receptor (AT1R) expression in obese EAT were significantly higher than that in control. In vitro, mature adipocytes treated with angiotensin II (Ang II) exhibited pronounced leptin synthesis and secretion by promoting AP-1 nuclear translocation via the AT1R-ROS-ERK1/2 pathway. Moreover, cardiac fibroblasts were incubated with obese rat EAT-conditioned medium (EAT-CM), plus various inhibitors. EAT-derived leptin promoted proliferation of cardiac fibroblasts associated with increased ERK1/2 phosphorylation and induced MMPs/TIMPs imbalance, stimulating upregulation of type I collagen via the JAK2/STAT3-TGF-β1/Smad3 pathway in cardiac fibroblasts of obese rats. Conclusions The paracrine effect of EAT-derived leptin on myocardial remodeling, inducing MMPs/TIMPs imbalance and promoting the proliferation of cardiac fibroblasts via activating ERK1/2 and JAK2/STAT3-TGF-β1/Smad3 pathway in obesity. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): the Nature Science Foundation of China (grant no. 81873513, 81600574, and 30871042)

scholarly journals Renal Changes in the Early Stages of Diet-Induced Obesity in Ovariectomized Rats

2014 ◽  
pp. 723-732
Author(s):  
L. S. B. AMARAL ◽  
J. A. SILVA ◽  
T. M. TRINDADE ◽  
W. B. D. RIBAS ◽  
C. L. MACEDO ◽  
...  
Keyword(s):  
Blood Pressure ◽  
High Fat Diet ◽  
Ovariectomized Rats ◽  
Nuclear Antigen ◽  
Standard Diet ◽  
Ang Ii ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Fractional Excretion Of Sodium ◽  
Renal Changes

The relationship between obesity and renal lesions, especially in low estrogen levels, has been less documented. The aim of this study was to assess the renal changes in diet-induced obesity in ovariectomized rats. Wistar rats were ovariectomized or sham-operated and divided into four groups: sham-operated rats fed a standard diet (SSD); ovariectomized rats fed a standard diet (OSD); sham-operated rats fed a high-fat diet (SHFD); ovariectomized rats fed a high-fat diet (OHFD). Body weight and blood pressure were measured weekly. The rats were killed 24 weeks after initiation of standard or high-fat diet treatment, the kidneys were removed for immunohistochemical and histological studies. Blood and urine samples were collected to quantify sodium, potassium and creatinine. OHFD rats presented increases in visceral adipose tissue, serum insulin levels, blood pressure and proteinuria, and a decrease in fractional excretion of sodium as well. Histological and morphometric studies showed focal alterations in the renal cortex. Expression of macrophages, lymphocytes, nuclear factor-kappa B (NF-kB), Proliferating Cell Nuclear Antigen (PCNA), angiotensin II (ANG II) and vimentin was greater in OHFD rats than in control rats. Thus, these results demonstrate that the high-fat diet in ovariectomized rats promoted renal function and structure changes, renal interstitial infiltration of mononuclear cells and increased expression of ANG II and NF-kB.

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