High-fat Diet Induction Research Articles

Effect of Multiple Types of High-fat Diet Induction on Gut Microbiota Profile and Butyrate Levels on NAFLD Rat Model

Dysbiosis, marked by a decline in Firmicutes (such as Clostridium spp.) and a rise in Proteobacteria (such as Escherichia coli), is recognized as a pathway linked to the progression of non-alcoholic fatty liver disease (NAFLD). High-fat food may influence the development of NAFLD. This study investigates the effect of different high-fat diets on gut microbiota composition and butyrate levels in a rat model. Four groups of Rattus norvegicus strain Wistar (n=27) were fed specific diets for 12 weeks: normal diet (ND, n=7), high-fat diet (HFD, n=6), western diet (WD, n=7), and high-fat-high-fructose diet (HFHFD, n=7). Stools were cultured on Eosin Methylene Blue (EMB) for Escherichia coli and Forget Fredette Agar (FFA) for Clostridium spp. Colonies were counted using Total Plate Count (TPC), and butyrate levels were measured with gas chromatography. Liver histology was assessed with the NAFLD activity score (NAS). Gut microbiota were analyzed using Crosstab and Chi-Square tests, and butyrate levels with the Kruskal-Wallis test. Butyrate levels decreased in NAFLD-inducing diet groups (HFD, WD, HFHFD) compared to ND (p=0.021). Escherichia coli colony counts were significantly higher in NAFLD-inducing diet groups (p=0.048), while Clostridium spp. counts were higher in ND (p=0.001). Liver histological changes, particularly in the WD group, resembled NAFLD. These findings imply that different high-fat diets can alter the gut microbiome, potentially influencing NAFLD development.

Alpha-amylase and alpha-glucosidase upregulated glucose homeostasis in high-fat fed wistar rats supplemented with cocoa flavonoid-rich aqueous

This study investigates the impact of cocoa (Theobroma Cacao L.) flavonoid-rich aqueous supplementation on alpha-amylase and alpha-glucosidase enzymes, influencing glucose homeostasis in Wistar rats. Over 12 weeks, Wistar rats underwent a high-fat diet induction for obesity. Group assignments included a negative control on a normal diet, a positive control on a normal diet with 600 mg/kg cocoa-containing flavonoid-rich water extract, a fat-treated group on a high-fat diet with the same cocoa extract, and an untreated fat group exclusively on a high-fat diet. The cocoa extract was orally administered for 14 days, evaluating various metabolic parameters. Results showed that the rats displayed improved glucose tolerance, reduced fasting serum glucose, and enhanced insulin sensitivity with increased alpha-amylase and alpha-glucosidase levels compared to the untreated high-fat group and controls. This study suggests that cocoa-derived polyphenols hold potential in mitigating high-fat diet-induced adverse effects on glucose metabolism by regulating the secretion of alpha-amylase and alpha-glucosidase in rats.

High-Fat Diet Enhances Platelet Activation and Is Associated with Proprotein Convertase Subtilisin Kexin 9: An Animal Study.

Platelet activation and proprotein convertase subtilisin kexin 9 (PCSK9) play pivotal roles in the progression of atherosclerosis to cardiovascular events. It has been reported that hyperlipidemia, a well-documented risk factors for cardiovascular diseases, tends increase platelet activation and PCSK9 expression. However, little is known about this specific mechanism, particularly how nutrition affects platelet activation and PCSK9 levels in hyperlipidemia conditions. This study aimed to assess how a high-fat diet influences platelet activation, its association with PCSK9, and the effects on blood pressure in an animal model. Here, male Wistar rats were divided into four groups, subjected to different high-fat diets for ten weeks with varying nutrient components. The results showed that high-fat diet-induced hypercholesterolemia and hypertriglyceridemia significantly increased the plasma levels of β-thromboglobulin (β-TG), p-selectin, and platelet factor 4 (PF-4). The blood pressure readings were also elevated post high-fat diet induction. Interestingly, the group with the highest percentage of saturated fatty acid and trans-fat exhibited the highest PCSK9 levels, along with the highest increase in plasma cholesterol, triglycerides, and platelet activation parameters. These findings confirm that high-fat diet-induced hypercholesterolemia and hypertriglyceridemia stimulate platelet activity and PCSK9 levels. Moreover, our results suggest that PCSK9, implicated in hypercholesterolemia and hypertriglyceridemia, may synergistically mediate platelet hyperactivity, aligning with clinical studies. Notably, our results highlight the association between a high-fat diet and PCSK9, providing insights for drug discovery targeting platelet activation in atherosclerosis-induced cardiovascular diseases.

Protein Digestibility and Protein Efficiency Ratio of Herbal Rice by Rats Given High Fat Diet

Herbal rice made from white rice by adding a mixture of turmeric, cinnamon and guava leaves during cooking, reducing cholesterol levels in hypercholesterolemia. This study was aims to evaluate the protein digestibility and protein efficiency ratio of herbal rice by rats given high fat diet. This study used 28 male Spangue dawley rats aged 12 weeks divided into four treatment groups (7 rats per group). The control group (P0) was given standard diet AIN-76 without high fat diet induction, the treatment group (P1) was containing plain rice flour with high fat diet induction, the treatment group (P2) was containing cooked rice flour 1 bag of mixed herbs with high fat diet induction, and the treatment group (P3) was containing cooked rice flour 2 bags of herbal mixture with high fat diet induction. The results showed that the body weight of each rat treatment group increased during the 28 days of the experiment. The type of ration given had a significant effect (p<0.05) on the value of protein digestibility, but had no significant effect (p<0.05) on the value of the protein efficiency ratio (PER). Result evaluation of body weight, protein digestibility and PER of herbal rice obtained, it can be concluded that herbal rice has better protein quality than plain white rice.

Grain-sized moxibustion at Zusanli (ST36) promotes hepatic autophagy in rats with hyperlipidemia by regulating the ULK1 and TFEB expression through the AMPK/mTOR signaling pathway

ObjectiveGrain-sized moxibustion is an effective treatment for hyperlipidemia, but how it regulates dyslipidemia and liver lipid deposits still needs to be fully understood. This study explored the molecular biological mechanism of grain-sized moxibustion to regulate hepatic autophagy in hyperlipidemic rats by affecting ULK1 and TFEB through the AMPK/mTOR signaling pathway. MethodsThirty male Sprague-Dawley (SD) rats were fed a high-fat diet for eight weeks to induce hyperlipidemia. Hyperlipidemic rats were divided into the HFD group, HFD + Statin group, HFD + CC + Moxi group, and grain-sized moxibustion intervention group (HFD + Moxi group). The control (Blank) group consisted of normal rats without any intervention. Grain-sized moxibustion and drug interventions were initiated eight weeks after high-fat diet induction and continued for ten weeks. Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), as well as hepatic triglyceride (TG), were measured after treatment. Hepatic steatosis and the expression of LC3I, LC3II, p62, p-AMPK, AMPK, p-mTOR, mTOR, ULK1, p-ULK1, and TFEB in the liver were analyzed. ResultsCompared with the HFD group, grain-sized moxibustion improved hyperlipidemia and hepatocyte steatosis, increased the LC3, p-AMPK, p-ULK1, and nuclear TFEB expression in the liver, but decreased the p62 and p-mTOR expression. ConclusionGrain-sized moxibustion at ST36 acupoints could regulate the blood lipid level of SD rats with hyperlipidemia, increase the expression level of ULK1 and TFEB by activating the AMPK/mTOR signaling pathway in liver tissues, and initiate the transcription of autophagy genes such as LC3.

Modulation of Autophagy and Mitochondrial Dynamics Gene Expression by Turmeric and Mangosteen Peel Extract

High fat diet (HFD) induces oxidative stress and mitochondrial dysfunction which culminates in fatty liver disease. Autophagy and mitochondrial dynamics are affected by HFD. Turmeric and mangosteen have potential roles as antioxidants and regulators of mitochondrial function in the liver. The study aims to examine the effect of turmeric and mangosteen peel extract on autophagy and mitochondrial dynamics in the liver after HFD induction. Five groups of animals (n=5) as used: negative control, positive control (HFD), turmeric (HFD + 270 mg/kg BW turmeric extract), mangosteen (HFD + mangosteen 270 mg/kg BW peel extract), and fenofibrate (HFD + 15 mg/kg BW fenofibrate). HFD was given for 7 weeks, continued by another 7 weeks plus treatment. Liver sections were extracted to conduct semi-quantitative PCR. Autophagy (LC3, p62), mitophagy (Pink1, Parkin, Bnip3), mitochondrial fission (Drp1, Fis1), and mitochondrial fusion (Opa1, Mfn1, Mfn2) gene expression were measured. LC3 (p=0.048), p62 (p=0.043), Pink1 (p=0.012), Bnip3 (p=0.010), Mfn1 (p=0.015), and Mfn2 (p=0.035) gene expressions were differed significantly, while Parkin (p=0.098) Drp1 (p=0.962), Fis1 (p=0.570), and Opa1 (p=0.055) gene expressions did not differ between groups. Both turmeric and mangosteen peel extract have positive effects by activating autophagy, mitophagy, and mitochondrial fusion in rat liver induced by HFD.

Polysaccharides from Artocarpus heterophyllus Lam. (jackfruit) pulp alleviate obesity by modulating gut microbiota in high fat diet-induced rats

Polysaccharides have attracted widely attention for their ability to alleviate obesity by regulating intestinal flora. The modulating effect of polysaccharides from Artocarpus heterophyllus Lam. (jackfruit) pulp (JFP-Ps) on the intestinal flora and body weight (BW) in obese individuals remains unclear. The present study aimed to investigate the regulatory effects of JFP-Ps on intestinal flora in obese rats. The obese rat model was established by continuous induction of high-fat diet for 12 weeks, and then changes in intestinal flora were determined by 16S rRNA sequencing after JFP-Ps intervention. Results showed that JFP-Ps restrained BW gain, improved serum lipid profile, increased number of operational taxonomic units, species abundance and diversity, modulated the composition of intestinal flora, and reversed the dysbiosis of intestinal flora caused by high-fat diet. Moreover, JFP-Ps restored intestinal microecology and enhanced the antioxidant capacity of obese rats by increasing the abundance of short-chain fatty acids-producing bacteria (Prevotellaceae_Ga6A1_group, Sphaerochaeta and Alloprevotella) and reactive sulfur species-producing bacterium (Ruminococcaceae). These findings reveal that JFP-Ps may be a promising prebiotic for the treatment of obesity by modulation of intestinal flora.

Asperuloside alleviates lipid accumulation and inflammation in HFD-induced NAFLD via AMPK signaling pathway and NLRP3 inflammasome

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a clinical pathological syndrome of hepatic parenchymal cell steatosis caused by excessive lipid deposition, which is the chronic liver disease with the highest incidence in China. Asperuloside (ASP), a kind of iridoid compound, possesses natural pharmacological effects of anti-tumor, anti-inflammatory, antioxidant and anti-obesity. However, whether ASP can improve NAFLD remains unclear. PurposeWe aimed to investigate the effect of ASP on NAFLD mice induced by high-fat diet (HFD), and explore its mechanism in vivo and in vitro. MethodsPharmacodynamics of ASP was studied by HFD induction in NAFLD mice. HepG2 cells were induced by palmitic acid (PA) as cell model to investigate the effect of ASP on lipid deposition and inflammatory infiltration. Expression of Adenosine monophosphate - activated protein kinase (AMPK) signaling pathway and NOD-like receptor pyrin containing 3 (NLRP3) inflammasome were detected by Western blot and RT-PCR. Cytokines IL-1β and TNF-α were detected by ELISA. ResultsASP alleviated liver injury and inflammatory damage in mice with NAFLD. In addition, ASP improved lipid deposition as well as inflammatory response in HFD-induced NAFLD mice and PA-stimulated HepG2 cells. ASP ameliorated lipid deposition and inflammatory response by regulating the p-AMPK/SREBP-1c signaling pathway and NLRP3 inflammasome. ConclusionOur results suggest that ASP improve lipid deposition and inflammatory infiltration in NAFLD mice via regulating the AMPK/SREBP-1c signaling pathway and NLRP3 inflammasome, which may be an effective candidate for the treatment of NAFLD.

Characteristics of intestinal microbiota in C57BL/6 mice with non-alcoholic fatty liver induced by high-fat diet.

As a representation of the gut microbiota, fecal and cecal samples are most often used in human and animal studies, including in non-alcoholic fatty liver disease (NAFLD) research. However, due to the regional structure and function of intestinal microbiota, whether it is representative to use cecal or fecal contents to study intestinal microbiota in the study of NAFLD remains to be shown. The NAFLD mouse model was established by high-fat diet induction, and the contents of the jejunum, ileum, cecum, and colon (formed fecal balls) were collected for 16S rRNA gene analysis. Compared with normal mice, the diversity and the relative abundance of major bacteria and functional genes of the ileum, cecum and colon were significantly changed, but not in the jejunum. In NAFLD mice, the variation characteristics of microbiota in the cecum and colon (feces) were similar. However, the variation characteristics of intestinal microbiota in the ileum and large intestine segments (cecum and colon) were quite different. Therefore, the study results of cecal and colonic (fecal) microbiota cannot completely represent the results of jejunal and ileal microbiota.

Interferon gamma mediates the reduction of adipose tissue regulatory T cells in human obesity

Decreased adipose tissue regulatory T cells contribute to insulin resistance in obese mice, however, little is known about the mechanisms regulating adipose tissue regulatory T cells numbers in humans. Here we obtain adipose tissue from obese and lean volunteers. Regulatory T cell abundance is lower in obese vs. lean visceral and subcutaneous adipose tissue and associates with reduced insulin sensitivity and altered adipocyte metabolic gene expression. Regulatory T cells numbers decline following high-fat diet induction in lean volunteers. We see alteration in major histocompatibility complex II pathway in adipocytes from obese patients and after high fat ingestion, which increases T helper 1 cell numbers and decreases regulatory T cell differentiation. We also observe increased expression of inhibitory co-receptors including programmed cell death protein 1 and OX40 in visceral adipose tissue regulatory T cells from patients with obesity. In human obesity, these global effects of interferon gamma to reduce regulatory T cells and diminish their function appear to instigate adipose inflammation and suppress adipocyte metabolism, leading to insulin resistance.

Transcription factor EB inhibits non-alcoholic fatty liver disease through fibroblast growth factor 21.

We sought to explore the potential role of transcription factor EB (TFEB) in the pathogenesis of the non-alcoholic fatty liver disease (NAFLD). An NAFLD mouse model was established by high-fat diet induction, and then "gain of function" and "loss of function" experiments were performed to determine the potential protective effects of TFEB on NAFLD using TFEB knockdown and TFEB-overexpressed mice. The mediating effect of FGF21 was verified by injection of recombinant mouse fibroblast growth factor 21 (rmFGF21) and knockout of FGF21, and the regulatory effect of TFEB on FGF21 was examined. Mechanistic target of rapamycin (mTOR), ribosomal S6 kinase, TFEB, and FGF21 are involved in the NAFLD process. Overexpression of TFEB in NAFLD mice could reverse lipid deposition and metabolic changes in NAFLD mice. RmFGF21 can reverse the aggravation of NAFLD by TFEB knockdown. Increased expression of TFEB alleviates NAFLD, possibly through upregulation of FGF21 expression by targeting the FGF21 promoter. This study may lay a basis for identifying new drug targets for NAFLD treatment. KEY MESSAGES: Transcription factor EB (TFEB) is involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), and fibroblast growth factor 21 (FGF21) exerts a significantly positive effect on NAFLD. In the current study, we found that starvation led to an increase in liver lipids, which was reversed by re-feeding. Phosphorylated mTOR, ribosomal S6 kinase, TFEB, and FGF21 are involved in the above process. The increased expression of TFEB in NAFLD mice by tail vein injection of Ad-TFEB could reverse lipid deposition and metabolic changes in NAFLD mice. TFEB upregulated FGF21 expression by targeting the promoter of FGF21. This study adds to our understanding of the potential role of TFEB on the progression of NAFLD. This study may lay a basis for identifying new drug target of NAFLD treatment.

Preventive Effects of Ilex Cornuta Aqueous Extract on High-Fat Diet-Induced Fatty Liver of Mice.

Objective To investigate the preventive effects of Ilex cornuta aqueous extract (ICAE) on high-fat diet (HFD)-induced fatty liver of mice and its mechanisms. Materials and Methods Twenty-six male KM (Kunming) mice were divided into 3 groups, including the control group (n = 9), fed with normal diet; HFD group (n = 9), fed with HFD; ICAE + HFD group (n = 8), fed with HFD and administered with ICAE (3 g·kg−1·d−1) at the same time for 10 weeks. Body weight, liver weight, intra-abdominal and subcutaneous fat weight, serum triglyceride (TG), total cholesterol (TC), and blood glucose were determined to evaluate the preventive effects of ICAE on obesity. The average 24 h food consumption of the mice was monitored for 5 times in the 9th week of the experiment to investigate the effects of ICAE on food intake. Serum alanine transaminase (ALT) and aspartate aminotransferase (AST) were assayed to observe the influences of HFD and ICAE on liver function. HE staining was adopted to observe the influence of ICAE on the morphology of adipose tissue and liver tissue. Hepatic TG and TC content assay and oil red O staining were used to evaluate the influences of ICAE on HFD-induced fatty liver, and the protein expression of peroxisome proliferator-activated receptors γ (PPARγ) and adipose differentiation-related protein (ADRP) in liver were examined by immunoblotting. Results ICAE treatment significantly reduced the increase of body weight, intra-abdominal, and subcutaneous fat and liver weight induced by HFD (P < 0.001), but has no influence on food intake; ICAE treatment attenuated the elevation of serum TG, TC, and glucose, as well as serum ALT and AST (P < 0.01, P < 0.05, P < 0.001) and dramatically decreased the content of TG in liver (P < 0.01), but has no influence on hepatic TC content. HE staining and oil red O staining showed that ICAE significantly reduced HFD-induced white adipocyte hypertrophy and significantly inhibited lipid accumulation in liver. Immunoblotting showed that the protein levels of PPARγ and ADRP were significantly increased by HFD induction, which can be dramatically reduced by ICAE treatment (P < 0.05, P < 0.0001). Conclusion ICAE has preventive effects on HFD-induced obesity and fatty liver in mice, exerted beneficial effects upon HFD-induced hepatic injury. The preventive effects of ICAE on fatty liver are concerned with the downregulation of PPARγ and ADRP protein expression in liver.

Hypolipidemic Effect and Liver Protection of Irpex lacteus Fermented Tea in Vivo

To study the effect of Irpex lacteus fermented tea on blood lipids and liver in mouse, 60 male KM mice were established hyperlipidemia model by high-fat diet induction, and then were randomly divided into six groups: Model group, simvastatin positive control group(10 mg/kg), green tea group(400 mg/kg) and high-(400 mg/kg), medium-(200 mg/kg), and low-(100 mg/kg) -dose Irpex lacteus fermented tea groups. And another 10 male KM mice were set up blank control group. The blank control group was given basic feeds, and the remaining groups were fed with high-fat feeds and gavage corresponding drugs. After 35 days, the body weight, liver weight and liver coefficient of each group were calculated. Serum total cholesterol(TC), triglyceride(TG), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), aspartate aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatase(ALP), superoxide dismutase(SOD), malondialdehyde(MDA) and glutathion peroxide(GSH) levels were detected, and morphological changes(HE) and liver fat particles(oil red O) in the liver of mice were observed. The results showed that high-(400 mg/kg) -dose Irpex lacteus fermented tea group could significantly reduce the levels of TC, LDL-C, AST, ALT, ALP and liver coefficient(P<0.05 or P<0.01), these indicators levels were close to the simvastatin group. High-(400 mg/kg) -dose Irpex lacteus fermented tea group significantly reduced TG level(P<0.01), and with the blank control group TG level, and increased HDL-C levels(P<0.01) in hyperlipidemic mice, the level of HDL-C was close to simvastatin group. It also could significantly reduce MDA content in liver and hyperlipidemia mice below simvastatin group, and increase SOD and GSH activity, which were close to blank control group and simvastatin group, respectively(P<0.05), improve the degree of fatty liver histopathology, and reduce liver fat particles. These findings indicated that the high-(400 mg/kg) -dose Irpex lacteus fermented tea group had hypolipidemic, improved the fatty liver disease and hepatoprotective effects by regulating oxidative stress in hyperlipidemic mice. This study would provide a theoretical basis for the development and utilization of the Irpex lacteus fermented tea as functional tea with anti-oxidation, lowering blood lipid and improving fatty liver.

MicroRNA-19b-3p-containing extracellular vesicles derived from macrophages promote the development of atherosclerosis by targeting JAZF1.

Atherosclerosis has been regarded as a major contributor to cardiovascular disease. The role of extracellular vesicles (EVs) in the treatment of atherosclerosis has been increasingly reported. In this study, we set out to investigate the effect of macrophages‐derived EVs (M‐EVs) containing miR‐19b‐3p in the progression of atherosclerosis, with the involvement of JAZF1. Following isolation of EVs from macrophages, the M‐EVs were induced with ox‐low density lipoprotein (LDL) (ox‐LDL‐M‐EVs), and co‐cultured with vascular smooth muscle cells (VSMCs). RT‐qPCR and western blot assay were performed to determine the expression of miR‐19b‐3p and JAZF1 in M‐EVs and in VSMCs. Lentiviral infection was used to overexpress or knock down miR‐19b‐3p. EdU staining and scratch test were conducted to examine VSMC proliferation and migration. Dual‐luciferase gene reporter assay was performed to examine the relationship between miR‐19b‐3p and JAZF1. In order to explore the role of ox‐LDL‐M‐EVs carrying miR‐19b‐3p in atherosclerotic lesions in vivo, a mouse model of atherosclerosis was established through high‐fat diet induction. M‐EVs were internalized by VSMCs. VSMC migration and proliferation were promoted by ox‐LDL‐M‐EVs. miR‐19b‐3p displayed upregulation in ox‐LDL‐M‐EVs. miR‐19b‐3p was transferred by M‐EVs into VSMCs, thereby promoting VSMC migration and proliferation. mir‐19b‐3p targeted JAZF1 to decrease its expression in VSMCs. Atherosclerosis lesions were aggravated by ox‐LDL‐M‐EVs carrying miR‐19b‐3p in ApoE−/− mice. Collectively, this study demonstrates that M‐EVs containing miR‐19b‐3p accelerate migration and promotion of VSMCs through targeting JAZF1, which promotes the development of atherosclerosis.

6-gingerol ameliorates metabolic disorders by inhibiting hypertrophy and hyperplasia of adipocytes in high-fat-diet induced obese mice

ObjectivesAccumulating studies revealed that 6-gingerol, a compound extracted mainly from ginger, treats obesity by preventing hyperlipidemia in vivo induced by high-fat-diet (HFD). The present study intends to further evaluate the efficacy of 6-gingerol in the treatment of obesity and investigate its potential mechanism. MethodsObese mice were established by HFD induction. Bioinformatic analysis was used to predict the possible pathways enrolled by the application of 6-gingerol. Body weight and the levels of blood glucose and lipids were examined and analyzed for the evaluation of the therapeutic effect of 6-gingerol. The size and amounts as well as the status of adipocytes were determined by histological staining. The expression levels of related proteins in adipose tissue were assessed by immunohistochemical staining, immunofluorescent staining, and Western blot analysis. In addition, the expression levels of related mRNA were assessed by RT-qPCR. ResultsHFD induced obesity was significantly curbed by 6-gingerol treatment. Here inhibition mechanism of 6-gingerol is demonstrated on excessive hypertrophy and hyperplasia of adipocytes in white adipose tissue (WAT), which may be related to the regulation of adipocytokines, such as PPARγ, C/EBPα, FABP4 and adiponectin, and the TLR3/IL-6/JAK1/STAT3 axis. Moreover, 6-gingerol treatment suppressed the expressions of IL-1β and CD68 in the liver and AKT/INSR/IRS-1 in epididymal WAT. ConclusionThe results suggested that 6-gingerol could alleviate metabolic inflammation in the liver and insulin resistance to treat obesity. The mechanism is mainly involved in the inhibition of excessive hypertrophy and hyperplasia of adipocytes.

Streptozotocin-induced type 1 and 2 diabetes in rodents: a model for studying diabetic cardiac autonomic neuropathy.

Several animal models are continually being developed to study diabetic complication. Several conflicting regimen for diabetes induction exist in the literature with varying dose strength and regimen for different study interest in diabetes. This study aims to show the effect of high dose streptozotocin (STZ) on the one hand compared with multiple low doses after high fat diet induction on diabetic cardiac autonomic neuropathy (DCAN). Eighty-four Wistar rats were used to demonstrate DCAN induction using 2 approaches one for T1DM (STZ 50mg/kg) and the other for T2DM (HFD for 8 weeks with STZ 25mg/Kg daily for five days). DCAN features were assessed using invasive biomarkers, histology patterns and cardiac nerve densities. Diabetes induction rate was 76% and 89% in T1DM and T2DM model respectively. T1DM group had significant weight loss, reduced c-peptide, and insulin level post induction. The T2DM additionally showed significantly higher total cholesterol and Homeostatic model assessment (HOMA) compared with control. Serum levels of catecholamine, choactase, nerve growth factor and cardiac nerve density confirms development of DCAN. High single dose of STZ and HFD with multiple low doses of STZ may be recommended for DCAN study in T1DM and T2DM rat model respectively.

Anti-Obesity Properties of Calocybe Indica in Zebra fishes with Short-Term High-Fat Diet Induction

Obesity, a disease involved with complex health problems, is indicated by increased BMI, triglyceride and cholesterol levels. Obese individuals are found to be highly susceptible to develop non-alcoholic fatty liver disease,cardiovascular diseases, and also type 2 diabetes mellitus. Synthetic drugs used for treating obesity have been found to be associated with side effects such as anxiety,sleeplessness,hypertension, and drug addiction. Research on natural productspossessing therapeutic biological activitieshasdiscoveredtheir potential to minimize or even completely eliminate such side effects. Medicinal properties ofCalocybe indica include antidiabetic, hypertensive, anticancer, anti-inflammatory, antibacterial, and hepatoprotective effects; however, its anti-obesity activity is obscure.In this study, the anti-obesity effects of Calocybe indicawere investigated using a diet-induced obese Zebrafish modeland compared with standard drug Atorvastatin.Results show that 200µg of C. indica was able to effectively bring down triglyceride levels (12.5± 0 mg/ml; normal control 12.7 ± 0.7 mg/ml), cholesterol (210± 15.9 mg; normal control =70.4± 0)and HMG COA Reductase levels (0.9± 0.03; normal = 1.2 ± 0.01). Excessive fat accumulation in the liver (steatohepatitis) reduced after treatment with C. indica to a greater extent than by treatment with standard drug Atorvastatin. 100 µg of C. indica was found to be optimum in decreasing the levels of the liver enzymes, AST (177.1±5.7 IU/L; normal control =177.7±43.02 IU/l), ALT (365.5±2.9 IU/L; normal control= 355.5±34.4 IU/l), and ALP (2.3±1.1μmoles of phenol liberated/mg of protein/min; normal control = 0.7±1.2 μmoles of phenol liberated/mg of protein/min).Whole-body Oil Red O staining of the zebrafishes showed that with increasing concentration of C. indica, the accumulation of triglycerides and lipids decreased.

The Antioxidant Effect of Noni Fruits Extract on HDL and LDL Level of Wistar Rat Induced by High Fat Diet

Dyslipidemia is an important risk factor for myocardial infarction, cardiovascular diseases, and Nonalcoholic Fatty Liver (NAFLD) disorders. Inflammatory conditions, oxidative stress, and insulin resistance,as well as several risk factors for cardiovascular disease, are also risk factors for this disease. This study aimsto determine the effect of noni (Morinda citrifolia) extract on the improvement of dyslipidemia condition,based on the Low Density Lipoprotein (LDL) and High Density Lipoprotein (HDL) level. This research is alaboratory experimental study with a post-test only control group design. Male Wistar rat (Rattus norvegicus)were divided into four groups: negative control group with no induction and treatment (K-), positive controlgroup given high-fat diet induction for 14 days (K+), noni extract treatment group given a high-fat diet anda noni extract at a dose of 100 mg/kg BB per day for 7 days (P1), and noni extract at a dose of 200 mg/kgBB per day for seven days (P2). Low Density Lipoprotein and High Density Lipoprotein serum levels weremeasured using the ELISA method. The results showed that there was a significant increase in LDL and adecrease in HDL in both treatment groups (P1 and P2) compared with K(+) group. Therefore, we concludethat noni extract (Morinda citrifolia) played a role as an antioxidant which can increase LDL and decreaseHDL serum levels in rats induced by a high fat diet.

High-Fat Diet-Induced Trefoil Factor Family Member 2 (TFF2) to Counteract the Immune-Mediated Damage in Mice

Simple SummaryHigh-fat (HF) diet induces both immune-mediated damage and trefoil factor family member 2 (Tff2) expression. As TFF2 has tissue repair and protection properties, this suggests that HF diet-induced Tff2 production and the resulting TFF2 mucosal protective effects would be a mechanism to counteract the HF diet-induced tissue damage. On the other hand, the induction of Tff2 by HF diet could indicate that TFF2 is a food intake regulator (appetite control) since Tff2 is also expressed in the brain. This highlights the importance of exploring TFF2-related pathways in the context of obesity management towards potential therapies.Physiological homeostasis requires a balance between the immunological functions and the resulting damage/side effects of the immunological reactions including those related to high-fat (HF) diet. Within this context, whereas HF diet, through diverse mechanisms (such as inflammation), leads to immune-mediated damage, trefoil factor family member 2 (Tff2) represents a HF diet-induced gene. On the other hand, TFF2 both promotes tissue repair and reduces inflammation. These properties are towards counteracting the immune-mediated damage resulting from the HF diet. These observations suggest that the HF diet-induction of Tff2 could be a regulatory pathway aiming to counteract the immune-mediated damage resulting from the HF diet. Interestingly, since Tff2 expression increases with HF diet and with Tff2 also expressed in the brain, we also hypothesize that TFF2 could be a HF diet-induced food intake-control signal that reduces appetite. This hypothesis fits with counteracting the immune damage since reducing the food intake will reduce the HF intake and therefore, reduces the HF diet-induced tissue damage. Such food intake signaling would be an indirect mechanism by which TFF2 promotes tissue repair as well as a pathway worth exploring for potential obesity management pharmacotherapies.

Analog Rice Reduces Weight and Total Cholesterol Levels in Overweight and Hypercholesterolemic Rats

Overweight, whose prevalence is increasing, is caused by unbalanced consumption patterns such as high consumption of fat and can trigger hypercholesterolemia. Analog rice (AR), which has better nutritional content than ordinary rice, is thought to have beneficial effects on health. This study aimed to determine the potential of analog rice in reducing body weight and total cholesterol levels. A total of 24 male Wistar rats were divided into four groups, namely: I) control, II) ordinary rice treatment, III) analog rice 1 treatment (PBA1) and IV) analog rice 2 treatment (PBA2). The control group was given standard feed for 40 days ad libitum. Groups II, III, and IV were given a combination induction of high-fat diet (HFD) for 40 days ad libitum and intraperitoneal injection of streptozotocin (STZ) 35 mg/kg single dose on day 33. All groups were then given the treatment of diet for three weeks according to their respective groups, namely the standard, ordinary rice, analog rice 1, and analog rice 2 feed. Body weight and total cholesterol levels were measured in the pre-induction, post-induction/pre-treatment (pre-test), and post-treatment (post-test). The results of the study showed that the induction of the HFD-STZ combination carried out resulted in a significant increase in body weight and total cholesterol levels. Measurements made after dietary therapy showed that body weight and total cholesterol levels in the I and II groups did not change significantly, whereas those in the III and IV groups decreased significantly (p&lt;0.05). This study concluded that the administration of analog rice could reduce body weight and total cholesterol levels in overweight and hypercholesterolemia rats.Â