scholarly journals Effects of Soothing Liver and Invigorating Spleen Recipes on the IKKβ-NF-κB Signaling Pathway in Kupffer Cells of Nonalcoholic Steatohepatitis Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Xiang-Wen Gong ◽  
Yong-Jian Xu ◽  
Qin-He Yang ◽  
Yin-Ji Liang ◽  
Yu-Pei Zhang ◽  
...  
Keyword(s):  
Liver Function ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Kupffer Cells ◽  
Nonalcoholic Steatohepatitis ◽  
High Fat Diet ◽  
Liver Tissue ◽  
Male Rats ◽  
High Fat ◽  
Mrna And Protein Expression

This study investigates the effect of soothing liver and invigorating spleen recipes on steatohepatitis examining the IKKβ-NF-κB signaling pathway in KCs of NASH rats. SD male rats were randomly divided into 8 groups, and the NASH model was induced by a high-fat diet (HFD). After 26 weeks, liver tissue was examined in H&E stained sections and liver function was monitored biochemically. KCs were isolated by Seglen’s method, with some modifications. The mRNA and protein expression of the IKKβ-NF-κB signaling pathway components was examined by quantitative PCR and Western blotting. The results show that the high-fat diet induced NASH in the rats, and the soothing liver recipe and invigorating spleen recipe decreased the levels of TNF-α, IL-1, and IL-6 in KCs, as well as inhibiting the mRNA and protein expression of the IKKβ-NF-κB signaling pathway components. In conclusion, the experiment indicated the importance of the IKKβ-NF-κB signaling pathway in KCs for the anti-inflammatory effects of the soothing liver and invigorating spleen recipes.

scholarly journals Novel regulation of renal gluconeogenesis by Atp6ap2 in response to high fat diet via PGC1-α/AKT-1 pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Safia Akhtar ◽  
Silas A. Culver ◽  
Helmy M. Siragy
Keyword(s):  
Protein Expression ◽  
High Fat Diet ◽  
Normal Diet ◽  
Receptor Expression ◽  
Wild Type ◽  
High Fat ◽  
Renal Gluconeogenesis ◽  
Mrna And Protein Expression ◽  
Polymerase Chain ◽  
Renal Expression

AbstractRecent studies suggested that renal gluconeogenesis is substantially stimulated in the kidney in presence of obesity. However, the mechanisms responsible for such stimulation are not well understood. Recently, our laboratory demonstrated that mice fed high fat diet (HFD) exhibited increase in renal Atp6ap2 [also known as (Pro)renin receptor] expression. We hypothesized that HFD upregulates renal gluconeogenesis via Atp6ap2-PGC-1α and AKT pathway. Using real-time polymerase chain reaction, western blot analysis and immunostaining, we evaluated renal expression of the Atp6ap2 and renal gluconeogenic enzymes, PEPCK and G6Pase, in wild type and inducible nephron specific Atp6ap2 knockout mice fed normal diet (ND, 12 kcal% fat) or a high-fat diet (HFD, 45 kcal% fat) for 8 weeks. Compared with ND, HFD mice had significantly higher body weight (23%) (P < 0.05), renal mRNA and protein expression of Atp6ap2 (39 and 35%), PEPCK (44 and 125%) and G6Pase (39 and 44%) respectively. In addition, compared to ND, HFD mice had increased renal protein expression of PGC-1α by 32% (P < 0.05) and downregulated AKT by 33% (P < 0.05) respectively in renal cortex. Atp6ap2-KO abrogated these changes in the mice fed HFD. In conclusion, we identified novel regulation of renal gluconeogenesis by Atp6ap2 in response to high fat diet via PGC1-α/AKT-1 pathway.

scholarly journals An ErChen and YinChen Decoction Ameliorates High-Fat-Induced Nonalcoholic Steatohepatitis in Rats by Regulating JNK1 Signaling Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Tian-hong Xie ◽  
Jun-xiang Li ◽  
Tang-you Mao ◽  
Yi Guo ◽  
Chen Chen ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Signaling Pathway ◽  
Nonalcoholic Steatohepatitis ◽  
High Fat Diet ◽  
Therapeutic Option ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serum Biochemistry ◽  
High Fat

ErChen and YinChen decoction (ECYCD) is an effective traditional Chinese medicine and has been widely used in traditional Chinese medicine to treat nonalcoholic steatohepatitis (NASH), with good curative effects. However, the specific mechanisms underlying these effects are unclear. In this study, we determined the efficacy of ECYCD in a high-fat diet-induced NASH rat model, established by 8-week administration of a high-fat diet. ECYCD was administered daily for 4 weeks, after which the rats were euthanized. The results demonstrated that ECYCD ameliorated high-fat diet-induced NASH, as evidenced by decreased liver indexes, reduced hepatic lipid deposition and liver injury, lower serum biochemistry markers (including low-density lipoprotein), and reduced HOMA-IR scores. Moreover, levels of free fatty acids, tumor necrosis factor, and malondialdehyde were decreased, whereas glutathione was increased in the liver. Serum high-density lipoprotein was also increased in the liver, and ECYCD regulated the c-Jun N-terminal kinase 1 (JNK1) signaling pathway by decreasing the levels of JNK1 protein,JNK1mRNA, activator protein- (AP-) 1 protein,AP-1mRNA, and phospho-insulin receptor substrate- (IRS-)1ser307and increasing phopsho-PKBser473levels. These results suggested that ECYCD could ameliorate high-fat diet-induced NASH in rats through JNK1 signaling. ECYCD may be a safe therapeutic option for the treatment of NASH.

scholarly journals Effects of Distinct n-6 to n-3 Polyunsaturated Fatty Acid Rations on Insulin Resistant and AD-like Phenotypes in High-Fat Diets-Fed APP/PS1 Transgenic Mice

2021 ◽  
Author(s):  
Xiaojun Ma ◽  
Yujie Guo ◽  
Pengfei Li ◽  
Jingjing Xu ◽  
Shengqi Dong ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Insulin Signaling ◽  
High Fat Diet ◽  
High Fat ◽  
Pufa Ratio ◽  
Pro Inflammatory Cytokines

Abstract Background: Type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) are two prevalent diseases with comparable pathophysiological features and genetic predisposition. Polyunsaturated fatty acids (PUFAs) are essential in maintaining normal brain function. However, little is known about the impact of dietary n-6/n-3 PUFA ratio on AD-like pathology, especially in high-fat diet (HFD)-fed AD model mice. Methods: In the present study, the APP/PS1 mice were treated with 60% HFD for 3.5 months to induced insulin resistance. After that, 45% HFD with different n-6/n-3 PUFA ratios (n-6/n-3=1:1, 5:1 or 16:1) was applied for additional 3.5 months treatment. Following the dietary intervention, the behavior of mice was observed using the Water maze. Following behavioral testing, the animals were euthanized, and serum and tissue samples were collected for biochemical, histological and pathological analyses and evaluation. Cortical fatty acid profile was measured by gas chromatography. Western Blot and immunohistochemistry methods were used to detect protein expression of molecules related to AD pathology and insulin signaling pathway(s) in the brain sample tissues. Immunofluorescence assay was used to uncover the expression and migration of NF-κB in the cortex. qPCR method was applied to determine the gene expression of cortical pro-inflammatory cytokines.Results: HFD caused insulin resistance, increased serum IL-6 and TNF-α level, elevated cortical soluble Aβ1-40, Aβ1-42 content, and increased brain n-6/n-3 PUFAs ratio in APP/PS1 mice. Increased APP and BACE1 protein expression and p-IR/IR ratio, but decreased pro-inflammatory cytokines mRNA expression was observed in the cortex from 60% HFD-fed APP/PS1 mice. N-3 PUFAs rich diet (n-6/n-3=1:1) relieved insulin resistance and hyperlipidemia induced by 60% HFD. Cortical soluble Aβ1-40 and Aβ1-42 contents, the expression of cortical APP, GLUT3, insulin metabolism related molecules, and NF-κB pathway downstream pro-inflammatory cytokines showed a dietary n-6/n-3 PUFAs ratio-dependent way, indicating that dietary n-6/n-3 PUFA ratio plays a critical role in modifying the responses of serum inflammatory cytokine, AD pathology, cortical n-6/n-3 PUFAs ratio, insulin signaling and neuroinflammation to HFD treatment.Conclusion: Dietary n-6/n-3 PUFA ratio play an important role in modifying AD pathophysiology, insulin signaling pathway, and neuro-inflammation response to high fat diet treatment in brain.

Effects of obesity and exercise on testicular leptin signal transduction and testosterone biosynthesis in male mice

2017 ◽  
Vol 312 (4) ◽  
pp. R501-R510 ◽  
Author(s):  
Xuejie Yi ◽  
Haining Gao ◽  
Dequan Chen ◽  
Donghui Tang ◽  
Wanting Huang ◽  
...  
Keyword(s):  
Protein Expression ◽  
High Fat Diet ◽  
Sperm Quality ◽  
Regulatory Protein ◽  
High Volume ◽  
Exercise Group ◽  
High Fat ◽  
Moderate Volume ◽  
Mrna And Protein Expression ◽  
Stat Pathway

To explore the role of the testicular leptin and JAK-STAT[leptin (LEP)-JAK-STAT] pathway in testosterone biosynthesis during juvenile stages and exercise for weight loss, male C57BL/6J mice were randomly divided into normal-diet and high-fat diet groups. After 10 wk, mice in the high-fat diet-fed group were further divided randomly into obese control, obese moderate-volume exercise, and obese high-volume exercise groups. Mice in the obese moderate-volume exercise group were provided with 2 h/day, 6 days/wk swimming exercise for 8 wk, and mice in the obese high-volume exercise group underwent twice the amount of daily exercise intervention as the obese moderate-volume exercise group. The results showed that a high-fat diet causes obesity, leptin resistance, inhibition of the testicular LEP-JAK-STAT pathway, decreased mRNA and protein expression of steroidogenic factor-1, steroidogenic acute regulatory protein, and the P-450 side-chain cleavage enzyme, a decrease in the serum testosterone-to-estradiol ratio, and declines in sperm quality parameters. Both moderate and high-volume exercise were able to reduce body fat and increase the mRNA and protein expression of LEP-JAK-STAT, but only moderate exercise significantly increased the mRNA and protein expression of steroidogenic factor-1, steroidogenic acute regulatory protein, and P-450 side-chain cleavage enzyme and significantly reversed the serum testosterone-to-estradiol ratio and sperm quality parameters. These findings suggest that by impairing the testicular LEP-JAK-STAT pathway, early-stage obesity inhibits the biosynthesis of testosterone and sexual development and reduces male reproductive potential. Long-term moderate and high-volume exercise can effectively reduce body fat and improve obesity-induced abnormalities in testicular leptin signal transduction, whereas only moderate-volume exercise can reverse the negative impacts of obesity on male reproductive function.

scholarly journals Salidroside Modulates Insulin Signaling in a Rat Model of Nonalcoholic Steatohepatitis

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Hongshan Li ◽  
Hao Ying ◽  
Airong Hu ◽  
Dezhou Li ◽  
Yaoren Hu
Keyword(s):  
Signaling Pathway ◽  
Rat Model ◽  
Insulin Signaling ◽  
Nonalcoholic Steatohepatitis ◽  
High Fat Diet ◽  
Metabolic Diseases ◽  
Insulin Signaling Pathway ◽  
Hepatic Tissue ◽  
Therapeutic Effects ◽  
High Fat

A growing body of evidence has shown the beneficial effects of salidroside in cardiovascular and metabolic diseases. This study aimed to evaluate the therapeutic effects of salidroside on nonalcoholic steatohepatitis (NASH) in rats and explore the underlying mechanisms related to insulin signaling. A rat model of NASH was developed by high-fat diet for 14 weeks. From week 9 onward, the treatment group received oral salidroside (4.33 mg/kg) daily for 6 weeks. Salidroside effectively attenuated steatosis and vacuolation of hepatic tissue, with a dramatic decrease in liver triglycerides and free fatty acid levels (P < 0.01). Dysregulation of FINS, FBG, HOMA-IR, ALT, and AST in serum was ameliorated with salidroside treatment (P < 0.01). In the liver, salidroside induced significant increases in key molecules in the insulin signaling pathway, such as phosphorylated insulin receptor substrate 1 (IRS1), phosphoinositide 3-kinase (PI3K), and protein kinase B (PKB), with a significant decrease in SREBP-1c levels (P < 0.01). Therefore, salidroside effectively protected rats from high-fat-diet-induced NASH, which may be partially attributed to its effects on the hepatic insulin signaling pathway.

scholarly journals Radix Astragali Improves Dysregulated Triglyceride Metabolism and Attenuates Macrophage Infiltration in Adipose Tissue in High-Fat Diet-Induced Obese Male Rats through Activating mTORC1-PPARγSignaling Pathway

PPAR Research ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Yang Long ◽  
Xiang-Xun Zhang ◽  
Tao Chen ◽  
Yun Gao ◽  
Hao-Ming Tian
Keyword(s):  
Adipose Tissue ◽  
Signaling Pathway ◽  
High Fat Diet ◽  
Macrophage Infiltration ◽  
Male Rats ◽  
Epididymal Adipose Tissue ◽  
Radix Astragali ◽  
High Fat ◽  
Triglyceride Metabolism ◽  
Lowering Effect

Increased levels of free fatty acids (FFAs) and hypertriglyceridemia are important risk factors for cardiovascular disease. The effective fraction isolated from radix astragali (RA) has been reported to alleviate hypertriglyceridemia. The mechanism of this triglyceride-lowering effect of RA is unclear. Here, we tested whether activation of the mTORC1-PPARγsignaling pathway is related to the triglyceride-lowering effect of RA. High-fat diet-induced obese (DIO) rats were fed a high-fat diet (40% calories from fat) for 9-10 weeks, and 4 g/kg/d RA was administered by gavage. RA treatment resulted in decreased fasting triglyceride levels, FFA concentrations, and adipocyte size. RA treated rats showed improved triglyceride clearance and fatty acid handling after olive oil overload. RA administration could also decrease macrophage infiltration and expression of MCP-1 and TNFα, but it may also increase the expression of PPARγin epididymal adipose tissue from RA treated rats. Consistently, expressions of PPARγand phospho-p70S6K were increased in differentiated 3T3-L1 adipocytes treated with RA. Moreover, RA couldnot upregulate the expression of PPARγat the presence of rapamycin. In conclusion, the mTORC1-PPARγsignaling pathway is a potential mechanism through which RA exerts beneficial effects on the disturbance of triglyceride metabolism and dysfunction of adipose tissue in DIO rats.

scholarly journals Pioglitazone Upregulates Angiotensin Converting Enzyme 2 Expression in Insulin-Sensitive Tissues in Rats with High-Fat Diet-Induced Nonalcoholic Steatohepatitis

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Wei Zhang ◽  
Yi-Zhi Xu ◽  
Bo Liu ◽  
Rong Wu ◽  
Ying-Ying Yang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Angiotensin Converting Enzyme ◽  
Protein Expression ◽  
Hepatic Steatosis ◽  
Nonalcoholic Steatohepatitis ◽  
High Fat Diet ◽  
Ang Ii ◽  
Converting Enzyme ◽  
High Fat

Background and Aim.Thiazolidinediones (TZDs) can improve hepatic steatosis in nonalcoholic steatohepatitis (NASH). Angiotensin (Ang) II, the primary effector of renin-angiotensin system (RAS), plays vital roles in the development and progression of NASH. And some AngII-mediated effects can be regulated by TZDs. Angiotensin-converting enzyme (ACE) 2, a new component of RAS, can degrade Ang II to attenuate its subsequent physiological actions. We aimed to evaluate the effects of TZDs on ACE2 expression in insulin-sensitive tissues in NASH rats.Methods. Forty rats were divided into the normal control, high-fat diet (HFD), pioglitazone control, and HFD plus pioglitazone groups. After 24 weeks of treatment, we evaluated changes in liver histology and tissue-specific ACE2 expression.Results. ACE2 gene and protein expression was significantly greater in liver and adipose tissue in the HFD group compared with normal control group, while was significantly reduced in skeletal muscle. Pioglitazone significantly reduced the degree of hepatic steatosis compared with the HFD group. Pioglitazone significantly increased ACE2 protein expression in liver, adipose tissue, and skeletal muscle compared with the HFD group.Conclusions. Pioglitazone improves hepatic steatosis in the rats with HFD-induced NASH and upregulates ACE2 expression in insulin-sensitive tissues.

scholarly journals Effects of High-Fat Diet and Treadmill Running on The Hypothalamic Kiss-1-GPR54 Signaling Pathway in Growing Male Rats

2021 ◽  
Author(s):  
RUI XU ◽  
Junpeng FENG ◽  
Chunyu LIANG ◽  
Ge SONG ◽  
Yi YAN
Keyword(s):  
Signaling Pathway ◽  
High Fat Diet ◽  
Serum Testosterone ◽  
Exercise Group ◽  
Treadmill Running ◽  
Male Rats ◽  
Control Group ◽  
High Fat ◽  
Serum Samples ◽  
Diet And Exercise

Abstract Background: Kiss-1 neurons, one of the metabolic sensors in the hypothalamic, is necessary for puberty initiating and acts through G protein-coupled receptor, known as GPR54. This study investigated the mechanism of the hypothalamic Kiss-1-GPR54 signaling pathway in high-fat diet and exercise on the growing male rats. Methods: 135 three-week-old weaned male rats were underwent high-fat diet and exercise (60–70% VO2max, 1 h/day, 5 days/ week). These mice were randomly divided into control group, control and exercise group, high-fat diet group, high-fat diet and exercise group. Hypothalamic, testis, and serum samples of each group were collected at PND (postanal day)21st day (21D, early childhood), PND 43rd day (43D, puberty) and PND 56th day (56D, maturity). Immunofluorescence, Quantitative real-time PCR, hematoxylin and eosin staining, chemiluminescent immunoassays were used in studies. Analysis of variance (ANOVA) was used to analyze the effects of age (PND 21,43,56), exercise (exercise, sedentariness), and diet (high-fat, normal) on the biological indexes in ratsResults: The mRNA and protein expression of Kiss-1, GPR54 in the hypothalamic were gradually increased along with growing and peaked at PND 43, and the serum testosterone increased and peaked at PND 56. High-fat diet increased the expression of Kiss-GPR54 system in hypothalamic, while the serum testosterone decreased during different stages of growth. Exercise decreased the expression of Kiss-1 at PND 56 and increased the expression of Kiss-1at PND 43, meanwhile decreased testosterone and the deposition of lipid droplets in the testis at all age of development. Conclusions: The expression of Kiss-1-GPR54 in male rats showed fluctuated change during growth and development. High-fat diet can upregulate the expression of Kiss-1-GPR54 system in hypothalamic. Exercise can correct the adverse effect of high-fat diet on Kiss-1-GPR54 signaling pathway in hypothalamic and the function of hypothalamic-pituitary-testicular (HPT) axis, upregulate Kiss-1 at puberty and downregulate of Kiss-1 at maturity of high-fat diet male rats.

scholarly journals Perinatal high-fat diet alters development of GABAA receptor subunits in dorsal motor nucleus of vagus

2019 ◽  
Vol 317 (1) ◽  
pp. G40-G50 ◽  
Author(s):  
Courtney Clyburn ◽  
Caitlin A. Howe ◽  
Amy C. Arnold ◽  
Charles H. Lang ◽  
R. Alberto Travagli ◽  
...  
Keyword(s):  
Protein Expression ◽  
Gastric Motility ◽  
High Fat Diet ◽  
Cellular Localization ◽  
Developmental Regulation ◽  
Motor Nucleus ◽  
Sprague Dawley ◽  
High Fat ◽  
Dorsal Motor Nucleus ◽  
Mrna And Protein Expression

Perinatal high-fat diet (pHFD) exposure increases the inhibition of dorsal motor nucleus of the vagus (DMV) neurons, potentially contributing to the dysregulation of gastric functions. The aim of this study was to test the hypothesis that pHFD increases the inhibition of DMV neurons by disrupting GABAA receptor subunit development. In vivo gastric recordings were made from adult anesthetized Sprague-Dawley rats fed a control or pHFD (14 or 60% kcal from fat, respectively) from embryonic day 13 (E13) to postnatal day 42 (P42), and response to brainstem microinjection of benzodiazepines was assessed. Whole cell patch clamp recordings from DMV neurons assessed the functional expression of GABAA α subunits, whereas mRNA and protein expression were measured via qPCR and Western blotting, respectively. pHFD decreased basal antrum and corpus motility, whereas brainstem microinjection of L838,417 (positive allosteric modulator of α2/3 subunit-containing GABAA receptors) produced a larger decrease in gastric tone and motility. GABAergic miniature inhibitory postsynaptic currents in pHFD DMV neurons were responsive to L838,417 throughout development, unlike control DMV neurons, which were responsive only at early postnatal timepoints. Brainstem mRNA and protein expression of the GABAA α1,2, and 3 subunits, however, did not differ between control and pHFD rats. This study suggests that pHFD exposure arrests the development of synaptic GABAA α2/3 receptor subunits on DMV neurons and that functional synaptic expression is maintained into adulthood, although cellular localization may differ. The tonic activation of slower GABAA α2/3 subunit-containing receptors implies that such developmental changes may contribute to the observed decreased gastric motility. NEW & NOTEWORTHY Vagal neurocircuits involved in the control of gastric functions, satiation, and food intake are subject to significant developmental regulation postnatally, with immature GABAA receptors expressing slower α2/3-subunits, whereas mature GABAA receptor express faster α1-subunits. After perinatal high-fat diet exposure, this developmental regulation of dorsal motor nucleus of the vagus (DMV) neurons is disrupted, increasing their tonic GABAergic inhibition, decreasing efferent output, and potentially decreasing gastric motility.

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