High-fat Diet-induced Non-alcoholic Fatty Liver Research Articles

Effects of Acupuncture on the mRNA Expression of NF-κB p65/TNF-α Activated by Fat Accumulation in High-fat Diet-induced Nonalcoholic Fatty Liver Disease Rats

Effects of Acupuncture on the mRNA Expression of NF-κB p65/TNF-α Activated by Fat Accumulation in High-fat Diet-induced Nonalcoholic Fatty Liver Disease Rats

Ovothiol-A Mitigates High-Fat Diet-Induced Non-alcoholic Fatty Liver Disease in Rats

Background: Obesity is frequently linked to multiple comorbid and chronic illnesses, including non-alcoholic fatty liver disease, type 2 diabetes, cancer, and heart disease. Ovothiol-A is one of the most powerful natural antioxidants found in marine invertebrates like sea urchins. Objective: The current study aimed to investigate ovothiol-A's hypolipidemic and hypoglycemic potential in obese rats. Methods: All groups get a high-fat diet (HFD) for four weeks except for the control group. The control and HFD groups received distilled water, while the Ovothiol-A groups received two doses of Ovothiol-A (200 and 400 mg/kg orally) concurrent with HFD. Results: Weight gain, glucose, insulin, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, total cholesterol, triglycerides, low-density lipoprotein, malondialdehyde, and nitric oxide were all decreased after oral administration of Ovo at either the 200 or 400 mg/kg dose, while levels of high-density lipoprotein (HDL), glutathionereduced, catalase and glutathione-S-transferase increased. Histopathological alterations were less noticeable in the liver tissue of Ovothiol-A groups, with only a few vacuolated or pyknotic nuclei amongst a few dispersed hepatocytes. Conclusion: The current findings indicate that ovothiol-A protects against high-fat diet-induced fatty liver in rats. The anti-obesity mechanism of Ovothiol-A is associated with its hypolipidemic, hypoglycemic, and antioxidant properties.

Diosgenin ameliorating non-alcoholic fatty liver disease via Nrf2-mediated regulation of oxidative stress and ferroptosis.

This study aimed to investigate the mechanisms through which diosgenin inhibits the pathogenesis of non-alcoholic fatty liver disease, focusing particularly on ferroptosis-related pathways and its reliance on nuclear factor erythroid 2-related factor 2. Using a rat model, we showed diosgenin's efficacy in reducing lipid deposition throughout the body and examined its impact on ferroptosis-related gene expression in vivo. Moreover, in vitro experiments using human hepatocellular liver carcinoma cell line cells were conducted to assess oxidative stress and ferroptosis levels. Diosgenin decreased lipid accumulation and steatosis; lowered serum levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, glutamic pyruvic transaminase and glutamic oxaloacetic transaminase; reduced interleukin-1β and tumour necrosis factor-α; diosgenin decreased malondialdehyde levels; and increased serum superoxide dismutase levels in a rat model of high-fat diet-induced non-alcoholic fatty liver disease. Diosgenin upregulated the expression of nuclear factor erythroid 2-related factor 2 and its downstream ferroptosis-related genes to inhibit ferroptosis in the livers of rats with non-alcoholic fatty liver disease. Diosgenin decreased reactive oxygen species levels and enhanced the expression of ferroptosis-related genes in human hepatocellular liver carcinoma cells induced by free fatty acids, with its effects being dependent on nuclear factor erythroid 2-related factor 2. This study highlights the potential of diosgenin from Dioscoreaceae plants in mitigating oxidative stress and ferroptosis levels through nuclear factor erythroid 2-related factor 2 regulation, offering novel insights into the treatment of non-alcoholic fatty liver disease and other metabolic disorders through traditional Chinese medicine.

Chitosan-Stabilized Selenium Nanoparticles Alleviate High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease (NAFLD) by Modulating the Gut Barrier Function and Microbiota.

Low molecular weight chitosan selenium nanoparticles (LCS-SeNPs), a biologically active compound derived from selenium polysaccharides, have demonstrated potential in addressing obesity. However, the mechanism through which LCS-SeNPs alleviate high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) remains unclear. Our results elucidated that LCS-SeNPs significantly inhibited fat accumulation and markedly improved the intestinal barrier by increasing mucus secretion from goblet cells. Moreover, LCS-SeNPs reshaped intestinal flora composition by increasing the abundance of mucus-associated microbiota (Bifidobacterium, Akkermansia, and Muribaculaceae_unclassified) and decreasing the abundance of obesity-contributed bacterium (Anaerotruncus, Lachnoclostridium, and Proteus). The modulation of intestinal microbiota by LCS-SeNPs influenced several metabolic pathways, including bile acid secretion, purine metabolites, and tryptophan derivation. Meanwhile, glycocholic acid and tauro-beta-muricholic acid were significantly reduced in the LCS-SeNP group. Our study suggests the crucial role of intestinal microbiota composition and metabolism, providing a new theoretical foundation for utilizing selenium polysaccharides in the intervention of HFD-induced NAFLD.

Fanlian Huazhuo Formula alleviates high-fat diet-induced non-alcoholic fatty liver disease by modulating autophagy and lipid synthesis signaling pathway.

Fanlian Huazhuo Formula (FLHZF) has the functions of invigorating spleen and resolving phlegm, clearing heat and purging turbidity. It has been identified to have therapeutic effects on type 2 diabetes mellitus (T2DM) in clinical application. Non-alcoholic fatty liver disease (NAFLD) is frequently diagnosed in patients with T2DM. However, the therapeutic potential of FLHZF on NAFLD and the underlying mechanisms need further investigation. To elucidate the effects of FLHZF on NAFLD and explore the underlying hepatoprotective mechanisms in vivo and in vitro. HepG2 cells were treated with free fatty acid for 24 hours to induce lipid accumulation cell model. Subsequently, experiments were conducted with the different concentrations of freeze-dried powder of FLHZF for 24 hours. C57BL/6 mice were fed a high-fat diet for 8-week to establish a mouse model of NAFLD, and then treated with the different concentrations of FLHZF for 10 weeks. FLHZF had therapeutic potential against lipid accumulation and abnormal changes in biochemical indicators in vivo and in vitro. Further experiments verified that FLHZF alleviated abnormal lipid metabolism might by reducing oxidative stress, regulating the AMPKα/SREBP-1C signaling pathway, activating autophagy, and inhibiting hepatocyte apoptosis. FLHZF alleviates abnormal lipid metabolism in NAFLD models by regulating reactive oxygen species, autophagy, apoptosis, and lipid synthesis signaling pathways, indicating its potential for clinical application in NAFLD.

Comparative effects of viable Lactobacillus rhamnosus GG and its heat-inactivated paraprobiotic in the prevention of high-fat high-fructose diet-induced non-alcoholic fatty liver disease in rats.

Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver alterations worldwide, being gut microbiota dysbiosis one of the contributing factors to its development. The aim of this research is to compare the potential effects of a viable probiotic (Lactobacillus rhamnosus GG) with those exerted by its heat-inactivated paraprobiotic counterpart in a dietary rodent model of NAFLD. The probiotic administration effectively prevented the hepatic lipid accumulation induced by a high-fat high-fructose diet feeding, as demonstrated by chemical (lower TG content) and histological (lower steatosis grade and lobular inflammation) analyses. This effect was mainly mediated by the downregulation of lipid uptake (FATP2 protein expression) and upregulating liver TG release to bloodstream (MTTP activity) in rats receiving the probiotic. By contrast, the effect of the paraprobiotic preventing diet-induced liver lipid accumulation was milder, and mainly derived from the downregulation of hepatic de novo lipogenesis (SREBP-1c protein expression and FAS activity) and TG assembly (DGAT2 and AQP9 protein expression). The obtained results demonstrate that under these experimental conditions, the effects induced by the administration of viable L. rhamnosus GG preventing liver lipid accumulation in rats fed a diet rich in saturated fat and fructose differ from those induced by its heat-inactivated paraprobiotic counterpart.

Chiglitazar attenuates high-fat diet-induced nonalcoholic fatty liver disease by modulating multiple pathways in mice

Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide; however, effective intervention strategies for NAFLD are still unavailable. The present study sought to investigate the efficacy of chiglitazar, a pan-PPAR agonist, in protecting against NAFLD in mice and its underlying molecular mechanism. Male C57BL/6 J mice were fed a high-fat diet (HFD) for 8 weeks to generate NAFLD and the HFD was continued for an additional 10 weeks in the absence or presence of 5 mg/kg/d or 10 mg/kg/d chiglitazar by gavage. Chiglitazar significantly improved dyslipidemia and insulin resistance, ameliorated hepatic steatosis and reduced liver inflammation and oxidative stress in NAFLD mice. RNA-seq revealed that chiglitazar alleviated HFD-induced NAFLD in mice through multiple pathways, including fatty acid metabolism regulation, insulin signaling pathway, and AMPK signaling pathway. This study demonstrated the potential therapeutic effect of chiglitazar on NAFLD. Chiglitazar ameliorated NAFLD by modulating multiple pathways.

Platycodon D reduces obesity and non-alcoholic fatty liver disease induced by a high-fat diet through inhibiting intestinal fat absorption.

Platycodin D (PD) has been reported to treat metabolic diseases, including non-alcoholic fatty liver disease. In addition, platycodin D has been reported to activate intestinal 5'AMP-activated protein kinase (AMPK) phosphorylation levels, thereby reducing lipid absorption. Therefore, the aim of this study is to explore whether PD activation of intestinal AMPK and reduced lipid absorption can improve non-alcoholic fatty liver disease. Clean-grade male C57/BL mice were fed a high-fat diet (HFD) (containing 60% calories) for 16 weeks, and oral PD (10mg/kg/day) was administered at the same time. The liver and intestines were the collected, and the intestines were tested. The expressions of lipid absorption genes (CD36, NPC1L1, and ApoB), the serum total triglyceride (TG) and total cholesterol (TC) levels in the intestines and livers, the fecal free fatty acid (FFA) levels, and the expression of AMPK phosphorylated proteins in the intestines were examined using Western blot analyses. The lipid distribution in the livers, intestines, and fat was detected using Oil Red O and hematoxylin and eosin (H&E) staining. A colon cancer cell line (Caco2) was used to confirm the effect of PD on the cellular lipid uptake in vitro. In addition, serum inflammatory factors and liver enzymes were measured to clarify the impact of PD on the circulation of metabolic syndrome. Leptin-deficient mice (OB) were then used to further explore the improvement of PD on body weight and blood lipids. PD had a very significant therapeutic or preventive effect on metabolic syndrome and fatty liver induced by a high-fat diet. PD improved body weight, insulin sensitivity, and glucose tolerance in mice fed a high-fat diet and also prevented non-alcoholic fatty liver disease, reduced blood lipid levels, and increased fecal lipid excretion. In addition, PD reduced lipid absorption by activating the intestinal AMPK protein, which may have involved the inhibition of the gene expression levels of intestinal lipid absorption genes (CD36, NPC1L1, and ApoB). The combined effect of these factors improved hepatic lipid accumulation and lipid accumulation in adipose tissue. It was further found that PD also improved the body weights and blood lipid levels of leptin-deficient mice (OB) mice. PD had a very strong therapeutic effect on mice under a high-fat diet. PD reduced high-fat diet-induced obesity and non-alcoholic fatty liver disease by inhibiting intestinal fat absorption.

Coprococcus protects against high-fat diet-induced nonalcoholic fatty liver disease in mice.

The incidence of nonalcoholic fatty liver disease (NAFLD) is increasing annually, leading to substantial medical and health burdens. Numerous studies have demonstrated the potential effectiveness of intestinal probiotics as a treatment strategy for NAFLD. Therefore, the objective of this study is to identify a probiotic for the treatment of NAFLD. In this study, blood and fecal samples were collected from 41 healthy volunteers and 44 patients diagnosed with NAFLD. Analysis of the 16S rDNA sequencing data and quantitative real-time PCR (RT-qPCR) revealed a significant reduction in the abundance of Coprococcus in NAFLD patients. Subsequent animal experiments demonstrated that Coprococcus was able to effectively reverse liver lipid accumulation, inflammation, and fibrosis induced by a high-fat diet (HFD) in mice. This study provides the first in vivo evidence that Coprococcus is a beneficial bacterium capable of preventing NAFLD and has the same probiotic effect in mice as Lactobacillus GG (LGG), a positive control. Therefore, Coprococcus has the potential to serve as a probiotic for the prevention and treatment of NAFLD in humans.

Therapeutic potential of Lactobacillus casei and Chlorella vulgaris in high-fat diet-induced non-alcoholic fatty liver disease (NAFLD)-associated kidney damages: a stereological study.

The non-alcoholic fatty liver disease (NAFLD) is prevalent in as many as 25% of adults who are afflicted with metabolic syndrome. Oxidative stress plays a significant role in the pathophysiology of hepatic and renal injury associated with NAFLD. Therefore, probiotics such as Lactobacillus casei (LBC) and the microalga Chlorella vulgaris (CV) may be beneficial in alleviating kidney injury related to NAFLD. This animal study utilized 30 C57BL/6 mice, which were evenly distributed into five groups: the control group, the NAFLD group, the NAFLD + CV group, the NAFLD + LBC group, and the NAFLD + CV + LBC group. A high-fat diet (HFD) was administered to induce NAFLD for six weeks. The treatments with CV and LBC were continued for an additional 35 days. Biochemical parameters, total antioxidant capacity (TAC), and the expression of kidney damage marker genes (KIM 1 and NGAL) in serum and kidney tissue were determined, respectively. A stereological analysis was conducted to observe the structural changes in kidney tissues. A liver histopathological examination confirmed the successful induction of NAFLD. Biochemical investigations revealed that the NAFLD group exhibited increased ALT and AST levels, significantly reduced in the therapy groups (p < 0.001). The gene expression levels of KIM-1 and NGAL were elevated in NAFLD but were significantly reduced by CV and LBC therapies (p < 0.001). Stereological examinations revealed reduced kidney size, volume, and tissue composition in the NAFLD group, with significant improvements observed in the treated groups (p < 0.001). This study highlights the potential therapeutic efficacy of C. vulgaris and L. casei in mitigating kidney damage caused by NAFLD. These findings provide valuable insights for developing novel treatment approaches for managing NAFLD and its associated complications.

Identification of key genes involved in the alleviative effects of Polysaccharide of Atractylodes macrocephala Koidz on high-fat diet-induced nonalcoholic fatty liver disease in mice

Non-alcoholic fatty liver disease (NAFLD) is increasingly prevalent, but treatment options are limited. Previous studies have demonstrated the hepatoprotective effects of Polysaccharide of Atractylodes macrocephala Koidz (PAMK) against liver injury induced by various causes, but its potential in alleviating NAFLD remains unknown. This study aimed to investigate the potential of PAMK in improving NAFLD and its regulatory effects on gene transcription during the process. The results indicated that Highfatdiet (HFD) could induce NAFLD in mice, and PAMK was found to alleviate symptoms of NAFLD and mitigate liver injury caused by HFD. Transcriptome analysis revealed that PAMK affects both metabolic and inflammatory pathways, suggesting its dual impact on maintaining metabolic homeostasis and suppressing inflammation during NAFLD progression. The results of liver biochemical markers, key genes of the cholesterol pathway, glucose (GLU), and inflammatory factors further demonstrated the dual role of PAMK in metabolism and inflammation.

Would Combination Be Better: Swimming Exercise and Intermittent Fasting Improve High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease in Obese Rats via the miR-122-5p/SREBP-1c/CPT1A Pathway.

Swimming and intermittent fasting can both improve obesity-induced NAFLD, but which of the two is more effective and whether the combination of the two has a superimposed effect is inconclusive. The model of NAFLD in obese rats was established by a high-fat diet and performed swimming, intermittent fasting, and a combination of both interventions for 8 weeks. Serum lipids and enzyme activity were measured by an automatic biochemical analyzer. Liver morphostructural analysis was observed by transmission electron microscopy, and morphology was observed by HE staining. RT‒PCR was used to detect the mRNA level. Morphology and microstructure of the liver of model rats were impaired, with the upregulation of miR-122-5p, SREBP-1c, FASN and ACC1. Eight weeks of swimming exercise, intermittent fasting and the combination of both attenuate these effects, manifested by the downregulation of miR-122-5p and upregulation of CPT1A mRNA levels. There was no significant stacking effect of the combination of the swimming and intermittent fasting interventions. NAFLD leads to pathology in model rats. Eight weeks of swimming exercise, intermittent fasting and the combination of both can inhibit miR-122-5p and improve hepatic lipid metabolism, while no significant additive effects of combining the interventions were found.

Lipidomic Analysis of Liver and Adipose Tissue in a High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease Mice Model Reveals Alterations in Lipid Metabolism by Weight Loss and Aerobic Exercise.

Detailed investigation of the lipidome remodeling upon normal weight conditions, obesity, or weight loss, as well as the influence of physical activity, can help to understand the mechanisms underlying dyslipidemia in metabolic conditions correlated to the emergence and progression of non-alcoholic fatty liver disease (NAFLD). C57BL/6 male mice were fed a normal diet (ND) or a high-fat diet (HFD) for 20 weeks. Subgroups within the high-fat diet (HFD) group underwent different interventions: some engaged in exercise (HFDex), others were subjected to weight loss (WL) by changing from the HFD to ND, and some underwent a combination of weight loss and exercise (WLex) during the final 8 weeks of the 20-week feeding period. To support our understanding, not only tissue-specific lipid remodeling mechanisms but also the cross-talk between different tissues and their impact on the systemic regulation of lipid metabolism are essential. Exercise and weight loss-induced specific adaptations in the liver and visceral adipose tissue lipidomes of mice were explored by the UPLC-TOF-MS/MS untargeted lipidomics methodology. Lipidomic signatures of ND and HFD-fed mice undergoing weight loss were compared with animals with and without physical exercise. Several lipid classes were identified as contributing factors in the discrimination of the groups by multivariate analysis models, such as glycerolipids, glycerophospholipids, sphingolipids, and fatty acids, with respect to liver samples, whereas triglycerides were the only lipid class identified in visceral adipose tissue. Lipids found to be dysregulated in HFD animals are related to well-established pathways involved in the biosynthesis of PC, PE, and TG metabolism. These show a reversing trend back to basic levels of ND when animals change to a normal diet after 12 weeks, whereas the impact of exercise, though in some cases it slightly enhances the reversing trend, is not clear.

Potential Hepatoprotective Effect of Matricaria Pubescens on High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Rats.

This study aimed to identify the phytochemical compounds of Matricaria pubescens by LC-MS/MS and evaluate the potential protective effect of its supplementation in high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in adult rats through modulation of oxidative stress and histopathological changes. Twenty-four male rats were randomly divided into four groups. The first group served as control and received the standard diet. The second group (HFD) received a high-fat diet only (30 % of sheep fat). The third group's (control+MP) animals received a standard diet supplemented with 5 % M. pubescens (w/w). The fourth group (HFD+MP) received a high-fat diet supplemented with 5 % M. pubescens for 16 weeks. LC-MS/MS analysis showed that M. pubescens contains many phytochemical compounds. It was observed that the ethanolic extract of M. pubescens has a higher phenolic content than the aqueous extract. The supplementation of M. pubescens (5 % w/w) to HFD rats decreased significantly (p<0.01) body weight, liver and epididymal adipose tissue relative weights, glycemia, triglycerides (TG), insulin resistance, liver markers, TNF-α, malondialdehyde (MDA), protein carbonyl (PCO), advanced oxidation protein products (AOPP) level, and increased reduced glutathione (GSH) level, glutathione peroxidase (GPx), glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase activities as well as ameliorated histological alterations through the reduction hepatic lipid deposition and adipocytes hypertrophy compared to the HFD group. We conclude that M. pubescens powder may be effective for correcting hyperglycemia, hypertriglyceridemia, insulin resistance, and liver markers while decreasing inflammation and oxidative stress in the liver of high-fat diet-fed rats.

The therapeutic effect of alcoholic extract of Fumaria parviflora on high-fat diet-induced nonalcoholic fatty liver in rats: an animal experiment.

Nonalcoholic fatty liver disease (NAFLD) is a growing problem with a significant burden. Lifestyle modification is the recommended treatment, but researchers are exploring other options. This study focused on the effects of Fumaria parviflora (FP) extracts on NAFLD induced by a high-fat diet in rats. Thirty-five 10-week-old male Wister-Albino rats were divided into seven groups: normal diet control, high fat diet control, high fat diet with oral normal saline gavage, high fat diet with oral Atorvastatin gavage, and three groups receiving high fat diet with FP extract in 200mg/kg, 400mg/kg, and 700mg/kg.Blood samples of rats were used for the measurement of total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP).1×1cm Liver biopsies were taken, stained with Trichrome Stain (Masson) and Hematoxylin and eosin (H&E) stain for evaluation by a pathologist. Lab results showed that FP extract inhibits weight gain, has positive effects on triglyceride and alkaline phosphatase levels, and reduces hepatocyte ballooning and inflammation in rats. FP extract may lower liver enzymes and have a positive impact on triglyceride, LDL, and HDL levels in rats with NAFLD.

Bacteroides fragilis aggravates high-fat diet-induced non-alcoholic fatty liver disease by regulating lipid metabolism and remodeling gut microbiota.

Gut microbiota dysbiosis is a prominent determinant that significantly contributes to the disruption of lipid metabolism. Consequently, it is essential to the occurrence and development of non-alcoholic fatty liver disease (NAFLD). Nevertheless, the connection between diet and symbiotic gut microbiota in the progression of NAFLD remains uncertain. The purpose of this study was to explore the role of supplementing commensal Bacteroides fragilis (B. fragilis) on lipid metabolism, gut microbiota, and metabolites in high-fat diet (HFD)-fed mice, elucidating the impact of gut microbiota and metabolites on the development of NAFLD. Our study revealed that supplementation with B. fragilis exacerbated both weight gain and obesity in mice. B. fragilis exacerbated blood glucose levels and liver dysfunction in mice. Furthermore, an increase in liver lipid accumulation and the upregulation of genes correlated with lipid metabolism were observed in mice. Under an HFD, supplementation of commensal B. fragilis resulted in alterations in the gut microbiota, notably a significant increase in Desulfovibrionaceae, which led to elevated endotoxin levels and thereby influenced the progression of NAFLD. It was interesting that the simultaneous examination of gut microbiota metabolites revealed a more pronounced impact of diet on short-chain fatty acids. This study represented the pioneering investigation into the impact of B. fragilis on NAFLD. Our findings demonstrated that B. fragilis induced dysregulation in the intestinal microbiota, leading to elevated levels of lipopolysaccharide and dysfunction in glucose and lipid metabolism, thereby exacerbating NAFLD.IMPORTANCESome intestinal symbiotic microbes are involved in the occurrence of the metabolic disorders. Our study investigated the impact of supplementing commensal Bacteroides fragilis on host metabolism in high-fat diet-fed mice. Research results indicated that adding a specific bacterial strain to the complex intestinal microecology can worsen metabolic conditions. This effect mainly affects the structural diversity of intestinal microorganisms, the increase in harmful bacteria in the gut, and the elevation of endotoxin levels, blood glucose, and lipid metabolism, thereby impacting the progression of non-alcoholic fatty liver disease (NAFLD). Understanding the principles that govern the establishment of microbial communities comprising multiple species is crucial for preventing or repairing dysfunctions in these communities, thereby enhancing host health and facilitating disease treatment. This study demonstrated that gut microbiota dysbiosis could contribute to metabolic dysfunction and provides new insights into how to promote gut microbiota in the prevention and therapy of NAFLD.

Exploring the Regulatory Effect of Tegillarca granosa Polysaccharide on High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice Based on Intestinal Flora.

To explore the potential mechanism of action of Tegillarca granosa polysaccharide (TGP) in treating nonalcoholic fatty liver disease (NAFLD), the study conducts in vivo experiments using male C57BL/6 mice fed a high-fat diet while administering TGP for 16 weeks. The study measures body weight, liver weight, serum biochemical markers, pathological histology, liver lipid accumulation, oxidative stress and inflammation-related factors, lipid synthesis and metabolism-related gene and protein expression, and the composition and abundance of intestinal flora. Additionally, short-chain fatty acid (SCFAs) content and the correlation between intestinal flora and environmental factors are measured. The results show that TGP effectively reduces excessive hepatic lipid accumulation, dyslipidemia, abnormal liver function, and steatosis in the mice with NAFLD. Moreover, TGP effectively regulates intestinal flora disorder, increases the diversity of intestinal flora, and affects the relative abundance of specific bacteria while also increasing the content of SCFAs. These findings provide a basis for exploring the regulatory effect of T. granosa polysaccharide on NAFLD based on intestinal flora and highlight its potential as a natural liver nutraceutical.

Lauric acid attenuates hepato-metabolic complications and molecular alterations in high-fat diet-induced nonalcoholic fatty liver disease in rats

Nonalcoholic fatty liver disease (NAFLD) has emerged as a major chronic liver illness characterized by increase of lipid content in the liver. This study investigated the role of lauric acid to treat NAFLD in male adult Sprague Dawley rats. In this study, to induce NAFLD in the rats, a high-fat diet (HFD) was administered for eight consecutive weeks. Lauric acid groups received lauric acid (250 and 500 mg/kg; orally), concurrently with HFD for eight consecutive weeks. Lauric acid could ameliorate the serum levels of TG, TC, ALT, AST, blood glucose, and insulin. Moreover, lauric acid significantly elevated the levels of SOD, GSH, catalase, and IL-10. Additionally, it lowered the hepatic levels of MDA, ROS, MPO, 4-HNE, interleukin (IL)-1β, and tumor necrosis factor (TNF-α). Furthermore, lauric acid significantly up-regulated the hepatic expression of IRS1, AMPK, PI3K, and SIRT1 genes. In parallel, lauric acid could improve the histopathological picture of the liver and reduce the liver apoptosis via decreasing the expression of annexin V (Anx V). Finally, our data proposed that lauric acid could be an effective candidate for the NAFLD treatment.

Curcumin Ameliorates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease by Regulating Endoplasmic Reticulum Stress in The Liver

Curcumin Ameliorates High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease by Regulating Endoplasmic Reticulum Stress in The Liver

Deletion of the PPARδ gene exacerbates high-fat diet-induced nonalcoholic fatty liver disease in mice through the gut-liver axis

Deletion of the PPARδ gene exacerbates high-fat diet-induced nonalcoholic fatty liver disease in mice through the gut-liver axis