High-fat Diet Rats Research Articles

Saponins from Chenopodium quinoa Willd. husks alleviated high-fat-diet-induced hyperlipidemia via modulating the gut microbiota and multiple metabolic pathways.

Hyperlipidemia is characterized by abnormally elevated blood lipids. Quinoa saponins (QS) have multiple pharmacological activities, including antitumor, bactericidal and immune-enhancing effects. However, the lipid-lowering effect and mechanisms of QS in vivo have been scarcely reported. The effect of QS against hyperlipidemia induced by high-fat diet in rats was explored based on gut microbiota and serum non-targeted metabolomics. The study demonstrated that the supplementation of QS could reduce serum lipids, body weight, liver injury and inflammation. 16S rRNA sequencing demonstrated that QS mildly increased alpha-diversity, altered the overall structure of intestinal flora, decreased the relative richness of Firmicutes, the ratio of Firmicutes/Bacteroidetes (P < 0.05) and increased the relative richness of Actinobacteria, Bacteroidetes, Bifidobacterium, Roseburia and Coprococcus (P < 0.05). Simultaneously, metabolomics analysis showed that QS altered serum functional metabolites with respect to bile acid biosynthesis, arachidonic acid metabolism and taurine and hypotaurine metabolism, which were closely related to bile acid metabolism and fatty acid β-oxidation. Furthermore, QS increased protein levels of farnesoid X receptor, peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase 1, which were related to the screened metabolic pathways. Spearman correlation analysis showed that there was a correlation between gut microbiota and differential metabolites. QS could prevent lipid metabolism disorders in hyperlipidemic rats, which may be closely associated with the regulation of the gut microbiota and multiple metabolic pathways. This study may provide new evidence for QS as natural active substances for the prevention of hyperlipidemia. © 2023 Society of Chemical Industry.

Hypolipidemic, Hypoglycemic, and Ameliorative Effects of Boiled Parsley (Petroselinum crispum) and Mallow (Corchorus olitorius) Leaf Extracts in High-Fat Diet-Fed Rats.

Obesity is a major health concern associated with serious conditions such as type 2 diabetes and cardiovascular diseases. This study investigated the potential anti-obesity effects of heat-treated parsley and mallow extracts (PE and ME, respectively) in high-fat diet (HFD)-fed rats. The selected herbs underwent three heat treatments (boiling, blanching, and microwaving), and the most effective treatment was orally administered to the HFD rats for eight weeks. All three treatments effectively increased the total phenolic content (TPC) and antioxidant capacity of the herbs, with boiling treatment exhibiting the most significant increase. Boiled herbs demonstrated approximately 29% higher TPC and an impressive 348% increase in antioxidant activity compared to the other treatments. Oral administration of the boiled herb extracts to the HFD rats resulted in significant reductions in body weight, total cholesterol, triglycerides, and LDL cholesterol levels, while elevating the HDL cholesterol levels compared to the positive control rats. Additionally, the boiled herb extracts exhibited antioxidant, hepatoprotective, and nephroprotective effects. Notably, PE displayed more significant anti-obesity properties compared to ME, potentially due to higher TPC and antioxidant activity observed in PE compared to ME. In conclusion, this study highlights the potential positive effects of boiled parsley against obesity and recommends boiling treatment as the preferred method when heat treatment is required for herbs.

The Hepatic Antisteatosis Effect of Xanthohumol in High-Fat Diet-Fed Rats Entails Activation of AMPK as a Possible Protective Mechanism.

Obesity is the leading cause of non-alcoholic fatty liver disease by provoking hyperglycemia, hyperlipidemia, insulin resistance, oxidative stress, and inflammation. Low activity of AMP-activated protein kinase (AMPK) is linked to obesity, liver injury, and NAFLD. This study involves examining if the anti-steatosis effect of Xanthohumol (XH) in high-fat diet (HFD)-fed rats involves the regulation of AMPK. Adult male rats were divided into five groups (n = 8 each) as control (3.85 kcal/g); XH (control diet + 20 mg/kg), HFD (4.73 kcl/g), HFD + XH (20 mg/kg), and HFD + XH (30 mg/kg) + compound c (cc) (0.2 mg/kg). All treatments were conducted for 12 weeks. Treatment with XH attenuated the gain in body weight, fat pads, fasting glucose, and insulin in HFD rats. It also lowered serum leptin and free fatty acids (FFAs) and improved glucose and insulin tolerances in these rats. It also attenuated the increase in serum livers of liver marker enzymes and reduced serum and hepatic levels of triglycerides (TGs), cholesterol (CHOL), FFAs, as well as serum levels of low-density lipoproteins cholesterol (LDL-c) oxidized LDL-c. XH also reduced hepatic levels of malondialdehyde (MDA), nuclear accumulation of NF-κB, and the levels of tumor necrosis-factor-α (TNF-α) and interleukin-6 (IL-6) while stimulating the nuclear levels of Nrf2 and total levels of glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) in these HFD-fed rats. At the molecular levels, XH increased hepatic mRNA expression and phosphorylation of AMPK (Thr72) and reduced the expression of lipogenic genes SREBP1c and ACC-1. In concomitance, XH reduced hepatic liver droplet accumulation, reduced the number of apoptotic nuclei, and improved the structures of nuclei, mitochondria, and rough endoplasmic reticulum. Co-treatment with CC, an AMPK inhibitor, completely abolished all these effects of XH. In conclusion, XH attenuates obesity and HFD-mediated hepatic steatosis by activating hepatic AMPK.

Renal effects of isolated resistance training in rats fed with high-fat diet

Aims: Regular physical activity is one of the most critical actions for treatment and prevention of obesity. Our aim is to evaluate the effects of resistance training in the inflammatory profile and renal damage promoted by high-fat diet in rats. Methods: Male Wistar rats were randomized into four groups: 12 weeks of a standard diet without (C) or with association with a 12 weeks resistance training program (RT), and high-fat diet without (HF) or with association with resistance training (HF-RT). Adiponectin, interleukin-6, leptin, MCP-1 and insulin were evaluated in plasma or serum. Glomerular size was analyzed by histology and total kidney content of mTOR, p-mTOR, PAI-1, STAT3 and p-STAT3 were quantified by western blot. Results: High-fat diet increased leptin, MCP-1 and TNF-α levels and resistance training normalized these levels in these animals. Glomerular tuff hypertrophy and renal increase in STAT, p-STAT3, mTOR and p-mTOR expression were observed in HF animals and normalized with RT. Conclusions: Our resistance training protocol had beneficial effects on proinflammatory state ang glomerular alterations in rats fed high-fat diet.

A Synergistic Botanical Composition Increases Resting Energy Expenditure and Reduces Adiposity in High-Fat Diet-Fed Rats

Objective An imbalance between dietary energy intake and energy expenditure may result in body fat gain or obesity. Increasing resting energy expenditure (REE) is an attractive strategy for managing body fat gain. The objective of the current study was to generate proof-of-concept data on a synergistic composition (LN19183) of Citrus aurantifolia fruit rind (CA) and Theobroma cacao seed (TC) extracts to increase REE and reduce body fat gain in a high-fat diet (HFD)–fed rats. Method In in vitro cell-based experiments, CA, TC, or LN19183 were tested for fibroblast growth factor 21 (FGF-21) production from 3T3-L1 mouse adipocytes. Uncoupling protein 1 (UCP-1) and beta3-adrenergic receptor (β3-AR) protein expressions in LN19183-treated 3T3-L1 lysates were also tested. The 56-day in vivo study in male Sprague Dawley (SD) rats (age: 12–14 weeks; body weight [b.w.]: 115–197 g) contained 2 phases of 28 days each of induction and supplementation. Seven rats received a regular rodent diet (RD) over 56 days. In the induction phase, 21 rats received HFD; in the supplementation phase, the obese rats (n = 7) received either HFD alone or in concurrence with a daily oral dose of either 100 or 250 mg/kg b.w. of LN19183 for 28 days. Results In 3T3-L1 adipocytes, LN19183 synergistically increased FGF-21 production and dose-dependently increased β3-AR and UCP-1 protein expression. In HFD-fed rats, both doses of LN19183 supplementation significantly (p < 0.05) decreased the body weight gain, total fat mass, and liver weight and increased (p < 0.05) REE. High-dose LN19183 also significantly (p < 0.05) increased fat oxidation and UCP-1 protein expression in white fat tissue and reduced liver triglyceride (TG) level. LN19183-supplemented groups substantially reduced serum TG and glucose levels compared to the HFD rats. Conclusions LN19183 reduces body fat mass and weight gain via increased REE and fat oxidation in HFD-fed obese rats.

Preparation of sn-2-acTAG from Polygala seed oil and a study on its hypolipidemic effect

A new class of 2-acetyl-1,3-diacyl-sn-glycerols (sn-2-acTAG) was found in the seed oil of Polygala previously. Its structure is very similar to sn-1,3-DAG, which has effect of preventing and treating hyperlipidemia and other diseases. In this study, sn-2-acTAG was enriched and confirmed, the safety and the hypolipidemic activity was assessed. In addition the mechanism of action was investigated. Our study indicated that a diet containing 20% sn-2-acTAG or lower was not toxic to SD rats. Compared to the soybean oil group, sn-2-acTAG could lower the total cholesterol, triglyceride, and high-density lipoprotein cholesterol levels, as well as rise the level of high-density lipoprotein cholesterol. Sn-2-acTAG could regulate the expression of proinflammatory factors to ameliorate hyperlipidemia. In conclusion, sn-2-acTAG has for the first time been found to significantly ameliorate hyperlipidemia in the high-fat diet rat. This study will provide a strong theoretical support for the efficient development and application of Polygala seed oil.

ß- Caryophyllene Ameliorates Insulin Resistance in Liver of High Fat Diet and Fructose-Induced Type-2 Diabetic Rats

Insulin resistance may impact organs that transmit insulin signals, like skeletal muscle, adipose tissue, and the liver. Hyperglycemia and hypertriglyceridemia in the fasting state of type 2 diabetes mellitus are more significantly impacted by insulin resistance in the liver. Hypertriglyceridemia is the culprit behind beta-cell failure in type 2 diabetes. Treating insulin resistance in liver as a primary mechanism of traditional antidiabetic drugs, but unfortunately traditional drugs has unalterable advisory effect. In the present research, insulin resistance in the liver is addressed with the versatile natural phytonutrient beta-caryophyllene to demonstrate effectiveness in managing diabetes. An effective dose of -Caryophyllene taken by non-parental route (200 mg/kg b.wt) was given for 30 days to experimentally induced (high-fat diet and fructose-fed) type-2 diabetic rats to find out whether β-Caryophyllene regulates the IRS-2/akt pathway of insulin signaling. In the liver of diabetic rats, the data demonstrates that ß-caryophyllene treatment significantly increased the mRNA and protein expression of insulin receptor (IR) and GLUT-2. However, there was a significant variation in the mRNA expression of akt and insulin receptor-substrate-2 (IRS-2) between groups. Taking caryophyllene supplements can be beneficial for the control of type 2 diabetes. Studies conducted with this sesquiterpene could have tremendous potential and benefit for the treatment of type 2 diabetes.

High-fat stimulation induces atrial neural remodeling by reducing NO production via the CRIF1/eNOS/P21 axi

BackgroundAutonomic remodeling of the atria plays a pivotal role in the development of atrial fibrillation (AF) and exerts a substantial influence on the progression of this condition. Hyperlipidemia is a predisposing factor for AF, but its effect on atrial nerve remodeling is unclear. The primary goal of this study was to explore the possible mechanisms through which the consumption of a high-fat diet (HFD) induces remodeling of atrial nerves, and to identify novel targets for clinical intervention.MethodsCell models were created in vitro by subjecting cells to palmitic acid (PA), while rat models were established by feeding them a high-fat diet. To investigate the interplay between cardiomyocytes and nerve cells in a co-culture system, we utilized Transwell cell culture plates featuring a pore size of 0.4 μm. The CCK-8 assay was employed to determine cell viability, fluorescent probe DCFH-DA and flow cytometry were utilized for measuring ROS levels, JC-1 was used to assess the mitochondrial membrane potential, the Griess method was employed to measure the nitric oxide (NO) level in the supernatant, a fluorescence-based method was used to measure ATP levels, and MitoTracker was utilized for assessing mitochondrial morphology. The expression of pertinent proteins was evaluated using western blotting (WB) and immunohistochemistry techniques. SNAP was used to treat nerve cells in order to replicate a high-NO atmosphere, and the level of nitroso was assessed using the iodoTMT reagent labeling method.ResultsThe study found that cardiomyocytes’ mitochondrial morphology and function were impaired under high-fat stimulation, affecting nitric oxide (NO) production through the CRIF1/SIRT1/eNOS axis. In a coculture model, overexpression of eNOS in cardiomyocytes increased NO expression. Moreover, the increased Keap1 nitrosylation within neuronal cells facilitated the entry of Nrf2 into the nucleus, resulting in an augmentation of P21 transcription and a suppression of proliferation. Atrial neural remodeling occurred in the HFD rat model and was ameliorated by increasing myocardial tissue eNOS protein expression with trimetazidine (TMZ).ConclusionsNeural remodeling is triggered by high-fat stimulation, which decreases the production of NO through the CRIF1/eNOS/P21 axis. Additionally, TMZ prevents neural remodeling and reduces the occurrence of AF by enhancing eNOS expression.

Assessment of melatonin's therapeutic effectiveness against hepatic steatosis induced by a high-carbohydrate high-fat diet in rats.

Several studies have demonstrated the protective effects of melatonin against metabolic diseases, such as liver steatosis. However, its therapeutic effects have received less scrutiny. The present study aimed to explore melatonin's therapeutic effectiveness in treating non-alcoholic fatty liver disease (NAFLD) induced by a high-carbohydrate high-fat (HCHF) diet in rats. The NAFLD was developed in male Wistar rats using an HCHF diet for 8 weeks. Afterward, they were given melatonin orally for four weeks at doses of 5 mg/kg, 10 mg/kg, and 30 mg/kg, along with the HCHF diet. In addition, six age-matched healthy rats received the highest dose of melatonin (30 mg/kg) for the same duration. Rats on the HCHF diet exhibited obesity, dyslipidemia, hyperglycemia, glucose intolerance, insulin resistance, inflammation, oxidative stress, and liver injury (steatosis). Melatonin treatment at 10 mg/kg and 30 mg/kg reduced body weight, adiposity index, oxidative damage, and inflammation but did not affect impaired glucose metabolism induced by the HCHF diet. Meanwhile, the highest dose of melatonin (30 mg/kg) reduced the liver steatosis index in HCHF rats but caused mild liver damage in healthy rats. In conclusion, using melatonin demonstrated positive outcomes in treating NAFLD induced by the HCHF diet in rats, with no noteworthy effects observed in healthy rats. A moderate dosage of 10 mg/kg of melatonin proved to be a safer and more efficient method for reducing HCHF diet-induced NAFLD in rats. Higher melatonin doses should be cautiously administered due to potential disruptions in lipid metabolism and the risk of liver complications.

Endoplasmic reticulum stress inhibitor may substitute for sleeve gastrectomy to alleviate metabolic dysfunction-associated steatotic liver disease

BackgroundMetabolic dysfunction-associated steatotic liver disease (MASLD) is becoming the most common form of chronic liver disease worldwide. We explored the potential mechanisms responsible for the protective role of sleeve gastrectomy (SG) on MASLD in a high-fat diet (HFD) rat model. MethodsRats were fed with HFD for 12 weeks to generate MASLD model that were subjected to SG or sham surgery. The endoplasmic reticulum stress (ERS) inhibitor 4-phenylbutyric acid (4-PBA) was injected intraperitoneally every day for 4 weeks after surgery to identify the impact of ERS. ResultsThe MASLD rat model was generated successfully, as indicated by significant upregulation of metabolic parameters. Fibroblast growth factor 21 (FGF21) and ERS-related proteins were increased in HFD rats, while expression of fibroblast growth factor receptor 1 was decreased as expected. An HFD also induced swelling and blurring of the endoplasmic reticulum and mitochondria in hepatocytes, and the above transformation could be relieved by SG and 4-PBA. SG and an ERS inhibitor both inhibited MASLD, but their combined treatment had no additional benefit. ConclusionsDysfunction of the FGF21 signaling pathway and hepatic steatosis and inflammation could be induced by an HFD, potentially causing MASLD. Bariatric surgery and ERS inhibition could alleviate MASLD by relieving ERS-mediated impairment of FGF21 signal transduction. These findings provide a new insight into the use of ERS inhibitors to treat MASLD, especially in patients who prefer to avoid surgery.

Telmisartan and candesartan promote browning of white adipose tissue and reverse fatty liver changes in high fat diet fed male albino rats.

This work is designed to explore the possible mitigated effects of Telmisartan and Candesartan cilexetil on weight gain and fatty liver in high fat diet (HFD) fed rats. The HFD rat model was achieved with induction of NAFLD. For Seven weeks either telmisartan or candesartan were orally administered at doses of 5 and 10 mg/kg respectively once daily. The effects of both drugs were evaluated by measurements of rat's body weight, food intakes, length, body mass index (BMI), liver weight, inguinal and interscapular fat weights. In addition, we assayed lipid profile, liver functions tests, serum inflammatory cytokines, adipokine and leptin. Lastly, liver and adipose tissue histopathological structures were evaluated. at end of experiment, telmisartan and candesartan were highly effective in decreasing rat's body weight from (213.1±2.68 to 191.2±2.54 and 203.5±5.89 gm , respectively), BMI, liver weight, fat weights in addition reduced serum levels of lipid and liver enzymes. Also, inflammatory cytokines were reduced with repaired histopathological insults in liver by significantly damped NAFLD score from (6.5 ±0.17 to 1±0 and 4 ±0, respectively) and decreased areas of adipocytes from (21239.12 to 5355.7 and 11607.1 um2 , respectively). Telmisartan and candesartan have therapeutic potential against obesity and NAFLD induced by HFD in rats. All the previous indices showed more improvement in telmisartan than candesartan group.

Diosgenin alleviates NAFLD induced by a high-fat diet in rats via mTOR/SREBP-1c/HSP60/MCAD/SCAD signaling pathway

This study aims to observe the effects of diosgenin on the expression of mammalian target of rapamycin(mTOR), sterol regulatory element-binding protein-1c(SREBP-1c), heat shock protein 60(HSP60), medium-chain acyl-CoA dehydrogenase(MCAD), and short-chain acyl-CoA dehydrogenase(SCAD) in the liver tissue of the rat model of non-alcoholic fatty liver disease(NAFLD) and explore the mechanism of diosgenin in alleviating NAFLD. Forty male SD rats were randomized into five groups: a control group, a model group, low-(150 mg·kg~(-1)·d~(-1)) and high-dose(300 mg·kg~(-1)·d~(-1)) diosgenin groups, and a simvastatin(4 mg·kg~(-1)·d~(-1)) group. The rats in the control group were fed with a normal diet, while those in the other four groups were fed with a high-fat diet. After feeding for 8 weeks, the body weight of rats in the high-fat diet groups increased significantly. After that, the rats were administrated with the corresponding dose of diosgenin or simvastatin by gavage every day for 8 weeks. The levels of triglyceride(TG), total cholesterol(TC), alanine transaminase(ALT), and aspartate transaminase(AST) in the serum were determined by the biochemical method. The levels of TG and TC in the liver were measured by the enzyme method. Oil-red O staining was employed to detect the lipid accumulation, and hematoxylin-eosin(HE) staining to detect the pathological changes in the liver tissue. The mRNA and protein levels of mTOR, SREBP-1c, HSP60, MCAD, and SCAD in the liver tissue of rats were determined by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) and Western blot, respectively. Compared with the control group, the model group showed increased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lipid deposition in the liver, obvious hepatic steatosis, up-regulated mRNA and protein expression levels of mTOR and SREBP-1c, and down-regulated mRNA and protein expression levels of HSP60, MCAD, and SCAD. Compared with the model group, the rats in each treatment group showed obviously decreased body weight, food uptake, liver index, TG, TC, ALT, and AST levels in the serum, TG and TC levels in the liver, lessened lipid deposition in the liver, ameliorated hepatic steatosis, down-regulated mRNA and protein le-vels of mTOR and SREBP-1c, and up-regulated mRNA and protein levels of HSP60, MCAD, and SCAD. The high-dose diosgenin outperformed the low-dose diosgenin and simvastatin. Diosgenin may prevent and treat NAFLD by inhibiting the expression of mTOR and SREBP-1c and promoting the expression of HSP60, MCAD, and SCAD to reduce lipid synthesis, improving mitochondrial function, and promoting fatty acid β oxidation in the liver.

Modulation of Xiongdanjiuxin pills on the gut-liver axis in high-fat diet rats

AimXiongdanjiuxin pill (XP) is a traditional Chinese medicine formula for the prevention and treatment of hyperlipidemia (HLP) and related complications. In this study, the gut-liver axis was used as the breakthrough point to analyze the therapeutic effect and potential mechanism of XP on HLP model rats and related complications. Main methodsWe used high-fat diet (HFD) to establish the HLP model of rats and treated them with XP. The 16S rRNA sequencing method was used to explore the effect of XP on the gut microbiota of HFD rats, and the effects of XP on ileum pathology, intestinal barrier and circulatory inflammation in HFD rats were also investigated. We further explored the molecular mechanism of XP treating liver inflammation in rats with HFD by regulating toll-like receptor 4 (TLR4) signaling. Key findingsWe found that XP could regulate the imbalance of gut microbiota in HFD rats, and up-regulate the expression of tight junction protein in intestinal epithelium of HFD rats, thereby improving the intestinal barrier damage and intestinal inflammatory response. In addition, XP could significantly reduce the levels of inflammatory cytokines in HFD rats, and inhibit TLR4 signaling pathway, thereby reducing liver inflammation in HFD rats. SignificanceXP can effectively improve the imbalance of gut-liver axis in hyperlipidemic rats and alleviate the inflammatory damage of liver. Its mechanism may be related to regulating the disorder of gut microbiota and inhibiting TLR4 signal pathway, so as to achieve the therapeutic effect on hyperlipidemic fatty liver in rats.

Altered Lipid Moieties and Carbonyls in a Wistar Rat Dietary Model of Subclinical Fatty Liver: Potential Sex-Specific Biomarkers of Early Fatty Liver Disease?

Non-alcoholic fatty liver disease (NAFLD) is a condition in which excess fat builds up in the liver. To date, there is a lack of knowledge about the subtype of lipid structures affected in the early stages of NAFLD. The aim of this study was to analyze serum and liver lipid moieties, specifically unsaturations and carbonyls, by nuclear magnetic resonance (NMR) in a subclinical Wistar rat model of NAFLD for detecting early alterations and potential sex dimorphisms. Twelve weeks of a high-fat diet (HFD) induced fat accumulation in the liver to a similar extent in male and female Wistar rats. In addition to total liver fat accumulation, Wistar rats showed a shift in lipid subtype composition. HFD rats displayed increased lipid carbonyls in both liver and serum, and decreased in unsaturated fatty acids (UFAs) and polyunsaturated fatty acids (PUFAs), with a much stronger effect in male than female animals. Our results revealed that the change in fat was not only quantitative but also qualitative, with dramatic shifts in relevant lipid structures. Finally, we compared the results found in Wistar rats with an analysis in a human patient cohort of extreme obesity. For the first time to our knowledge, lipid carbonyl levels and lipoproteins profiles were analyzed in the context of subclinical NAFLD. The association found between lipid carbonyls and alanine aminotransferase (ALT) in a human cohort of extremely obese individuals further supports the potential role of lipid moieties as biomarkers of early NAFLD.

The Effect of CV12, ST25, ST36 Acupuncture in General Diet and High Fat Diet Rat

The Effect of CV12, ST25, ST36 Acupuncture in General Diet and High Fat Diet Rat

Piezo1 channel activation facilitates baroreflex afferent neurotransmission with subsequent blood pressure reduction in control and hypertension rats.

Mechanosensitive cation channels such as Piezo1 and Piezo2 are activated by mechanical force like a starched wall of the aorta while blood pressure (BP) rising, which helps to elucidate the underlying mechanism of mechanotransduction of baroreceptor endings. In this study we investigated how Piezo1 channel activation-mediated gender- and afferent-specific BP regulation in rats. We established high-fat diet and fructose drink-induced hypertension model rats (HFD-HTN) and deoxycorticosterone (DOCA)-sensitive hypertension model rats. We showed that the expression levels of Piezo1 and Piezo2 were significantly up-regulated in left ventricle of HFD and DOCA hypertensive rats, whereas the down-regulation of Piezo1 was likely to be compensated by Piezo2 up-regulation in the aorta. Likewise, down-regulated Piezo1 was observed in the nodose ganglion (NG), while up-regulated Piezo2 was found in the nucleus tractus solitarius (NTS), which might synergistically reduce the excitatory neurotransmitter release from the presynaptic membrane. Notably, microinjection of Yoda1 (0.025-2.5 mg/ml) into the NG concentration-dependently reduced BP in both hypertensive rat models as well as in control rats with similar EC50; the effect of Yoda1 was abolished by microinjection of a Piezo1 antagonist GsMTx4 (1.0 μM). Functional analysis in an in vitro aortic arch preparation showed that instantaneous firing frequency of single Ah-fiber of aortic depressor nerve was dramatically increased by Yoda1 (0.03-1.0 μM) and blocked by GsMTx4 (1.0 μM). Moreover, spontaneous synaptic currents recorded from identified 2nd-order Ah-type baroreceptive neurons in the NTS was also facilitated over 100% by Yoda1 (1.0 μM) and completely blocked by GsMTx4 (3.0 μM). These results demonstrate that Piezo1 expressed on Ah-type baroreceptor and baroreceptive neurons in the NG and NTS plays a key role in a sexual-dimorphic BP regulation under physiological and hypertensive condition through facilitation of baroreflex afferent neurotransmission, which is presumably collaborated by Piezo2 expression at different level of baroreflex afferent pathway via compensatory and synergistic mechanisms.

Quinoa bran insoluble dietary fiber-zinc chelate mediates intestinal flora structure to regulate glucose and lipid metabolism in obese rats

Insoluble dietary fiber (IDF) and ZnSO4·7H2O were chelated to obtain the IDF-Zn. The Zn ion content was as high as 31.25 mg/g, which is a good source of Zn-rich products. The effects of IDF-Zn on metabolism and blood lipid levels were investigated in obese rats. Results showed that compared to IDF and organic Zn (ZnSO4·7H2O), IDF-Zn can significantly reduce the body weight, the levels of total cholesterol, triglycerides, and low-density lipoprotein cholesterol in serum, improve liver abnormal lipid sedimentation, oxidation stress state, and enhance the immunity of obese rats. Through 16S rRNA results, IDF-Zn intervention decreased the ratio of Firmicutes/Bacteroidetes and increased the abundance of probiotics (such as Lactobacillus, Muribaculaceae, and Bacteroides), and decreased the abundance of cellulolytic bacteria (such as Romboutsia and Clostridia-UCG-014). These results suggest that IDF-Zn can adjust intestinal flora structure of high-fat diet rats, promote liver health, reduce lipid deposits, and ultimately positively impact glucolipid metabolism.

Tirzepatide ameliorates spatial learning and memory impairment through modulation of aberrant insulin resistance and inflammation response in diabetic rats.

Background: One of the typical symptoms of diabetes mellitus patients was memory impairment, which was followed by gradual cognitive deterioration and for which there is no efficient treatment. The anti-diabetic incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) were demonstrated to have highly neuroprotective benefits in animal models of AD. We wanted to find out how the GLP-1/GIP dual agonist tirzepatide affected diabetes's impairment of spatial learning memory. Methods: High fat diet and streptozotocin injection-induced diabetic rats were injected intraperitoneally with Tirzepatide (1.35mg/kg) once a week. The protective effects were assessed using the Morris water maze test, immunofluorescence, and Western blot analysis. Golgi staining was adopted for quantified dendritic spines. Results: Tirzepatide significantly improved impaired glucose tolerance, fasting blood glucose level, and insulin level in diabetic rats. Then, tirzepatide dramatically alleviated spatial learning and memory impairment, inhibited Aβ accumulation, prevented structural damage, boosted the synthesis of synaptic proteins and increased dendritic spines formation in diabetic hippocampus. Furthermore, some aberrant changes in signal molecules concerning inflammation signaling pathways were normalized after tirzepatide treatment in diabetic rats. Finally, PI3K/Akt/GSK3β signaling pathway was restored by tirzepatide. Conclusion: Tirzepatide obviously exerts a protective effect against spatial learning and memory impairment, potentially through regulating abnormal insulin resistance and inflammatory responses.

Fucus vesiculosus polysaccharide alleviates type 2 diabetes in rats via remodeling gut microbiota and regulating glycolipid metabolism-related gene expression

The antidiabetic activity and underlying mechanisms of Fucus vesiculosus polysaccharide (FVP) were studied in type 2 diabetic rats. Our results exhibited that FVP intervention reversed body weight loss, alleviated hyperglycemia and insulin resistance in diabetic rats. FVP also had the potential to ameliorate dyslipidemia, liver and kidney dysfunction, decrease oxidative stress, promote glycogen synthesis, and boost short-chain fatty acid production and total bile acid excretion. 16S rRNA gene sequencing analysis suggested that FVP interfered with the gut microbiota in a beneficial manner. Moreover, RT-qPCR results demonstrated that the antidiabetic activity of FVP in connection with the acceleration of blood glucose absorption and glycogen synthesis, the inhibition of gluconeogenesis, and the regulation of lipid metabolism in the liver. These findings suggested that FVP had antidiabetic effects on high-fat diet and STZ-induced diabetic rats and could be a potential resource for treating type 2 diabetes mellitus.

The Potential Link between Obesity, Synbiotics Intake and Inflammasomes in an Animal Model

Abstract Background Obesity is one of the major public health problems worldwide, being considered a global epidemic. A growing body of evidence highlights the relevance of inflammasomes as a consequence of metabolic disorders and obesity. NLRP3 is the most studied component of the inflammasomes. Gut microbes contribute to the subclinical systemic inflammation that ultimately leads to the development of pathologies such as obesity, insulin resistance. Therefore, the use of intestinal microbiota modulators (e.g probitoics, prebiotics, or both as synbiotics) may improve several metabolic and immune functions. Recently, the link between these modulators and NLRP3 in obesity is less investigated. Aim of the Work to study the potential involvement of inflammasomes as an indicator for the efficacy of synbiotics in alleviating diet-induced obesity. Materials and Methods Thirty adult male Wistar rats were randomly divided into four groups (7 rats /group): normal control group (receiving normal diet), HFD (high fat diet) group, normal group receiving synbiotics, and HFD rats receiving synbiotics. After eight weeks, all rats were sacrificed then WAT (visceral, subcutaneous), brown adipose tissue, and liver were obtained. The body weight of each rat was measured weekly. The expression of NLRP3 was performed by real-time PCR. Results HFD induced a significant weight gain compared to normal diet (p &amp;lt; 0.05). However, synbiotics administration could not affect such weight gain in rats receiving HFD with synbiotics (p &amp;gt; 0.05). The expression of NLRP3, pre-inflammatory marker, is elevated in adipose and liver tissues in HFD group compared to normal diet group (p &amp;lt; 0.05). However, synbiotics successfully reduced the expression of NLRP3 in all previous tissues (p &amp;lt; 0.05). Conclusion the intake of synbiotics could disrupt the inflammatory consequences of obesity through targeting the expression of NLRP3. Thereby, synbiotics might be a promising potential therapeutic agent in treatment of obesity.