Lipid Accumulation In Liver Research Articles

RETRACTED: Echinacoside improves diabetic liver injury by regulating the AMPK/SIRT1 signaling pathway in db/db mice

Echinacoside (ECH) is a natural compound extracted from the stem of the Cistanche deserticola plant, has significant biological properties, including antioxidant, anti-inflammatory, neuroprotective, anti-tumor, hepatoprotective, and immunomodulatory properties. In this study, we aimed to explore the protection effects and mechanisms of ECH on diabetic liver injury in db/db mice. Overall, 6-week-old db/db mice (n=20) were randomly allocated to 2 groups: diabetic model group (db/db group, intragastric administration of normal saline, n=10) and ECH-treated group (db/db+ECH group, n=10). Additionally, the normal control group comprised 6-week-old db/m mice (db/m group, normal saline intragastric administration, n=10). ECH was administered once a day for 10weeks. Weight and fasting blood glucose (FBG) were measured biweekly. HE staining and Oil O staining were used to evaluate liver tissue pathological changes and lipid accumulation respectively. Immunofluorescence staining, Western blot and RT-PCR analysis were used to detect the expression of components of the AMPK/SIRT1 signaling axis. The results showed that the administration of echinacoside for 10weeks could significantly improve liver injury and insulin resistance in db/db mice (p<0.01). Also, echinacoside treatment helped to reduce blood lipids and blood glucose (p<0.01). Moreover, ECH actived AMPK/SIRT1 signaling, upregulated peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α), proliferator-activated receptor-α (PPARα), carnitine palmitoyl transferase-1A (CPT1A) in db/db mice (p<0.01). The effect of ECH may be elicited by the activation of the liver AMPK/SIRT1 pathway and its downstream factors to improve adiposity, insulin resistance, and dyslipidemia.

Nonalcoholic fatty liver disease as a metabolic disease in humans: A literature review.

AimsTo conduct a systematic literature review to identify recent epidemiological, biomarker, genetic and clinical evidence that expands our understanding of nonalcoholic fatty liver disease (NAFLD) as a metabolic disorder.Materials and MethodsWe performed a literature search using PubMed to identify trials, observational studies and meta‐analyses published in the past 5 years.ResultsA total of 95 publications met prespecified inclusion criteria and reported on the interplay between NAFLD/nonalcoholic steatohepatitis (NASH) and metabolic dysfunction, in terms of disease burden and/or epidemiology (n = 10), pathophysiology, risk factors and associated conditions (n = 29), diagnosis and biomarkers (n = 34), and treatment approaches (n = 22). There is a growing body of evidence on the links between NAFLD/NASH pathogenesis and mechanisms of metabolic dysfunction, through liver lipid accumulation, insulin resistance, inflammation, apoptosis, and fibrogenic remodelling within the liver. The frequent co‐occurrence of NAFLD with obesity, metabolic syndrome and type 2 diabetes supports this premise. Therapeutic approaches originally envisaged for type 2 diabetes or obesity (such as glucagon‐like peptide‐1 receptor agonists, sodium‐glucose co‐transporter‐2 inhibitors, insulin sensitizers and bariatric surgery) have shown promising signs of benefit for patients with NAFLD/NASH.ConclusionsGiven the complex interplay between NAFLD and metabolic dysfunction, there is an urgent need for multidisciplinary collaboration and established protocols for care of patients with NAFLD that are individualized and ideally support reduction of overall metabolic risk as well as treatment for NASH.

1,3-dichloro-2-propanol induced lipid accumulation by blocking autophagy flux in HepG2 cells

Great attention has been paid to 1,3-dichloro-2-propanol (1,3-DCP) due to its presence in food and concerns about toxic potential as carcinogens. In our previous study, we found that long-term low-dose 1,3-DCP exposure induced lipid accumulation in mouse liver. Recent studies have demonstrated that autophagy plays an important role in regulating lipid metabolism. So, we speculated that 1,3-DCP induced lipid accumulation by regulating autophagy in hepatocytes. In this study, we first studied the effect of 100 μM 1,3-DCP on autophagy flux in HepG2 cells. The data showed that 1,3-DCP (100 μM) impaired autophagy flux mainly through the attenuation of autophagosomes via AKT/mTOR signaling pathway and inhibition of lysosomes biosynthesis. Furthermore, we demonstrated that treatment with 100 μM 1,3-DCP for 24 h affected lipid metabolism through the colocalization of LC3 and Bodipy. We used an autophagy activator or an autophagy inhibitor to test the effect of 1,3-DCP on lipid accumulation through detecting lipid droplets staining, triglyceride (TG) and total cholesterol (TC). The data showed that 1,3-DCP-induced lipid accumulation was alleviated in the presence of Rapamycin (an autophagy activator). On the contrary, 1,3-DCP-induced lipid accumulation was significantly exacerbated in the presence of an autophagy inhibitor (3-methyladenine or chloroquine). These results suggested that 1,3-DCP might induce lipid accumulation by the impairment of autophagy flux in HepG2 cells.

Endothelial Cell Receptors in Tissue Lipid Uptake and Metabolism.

Lipid uptake and metabolism are central to the function of organs such as heart, skeletal muscle, and adipose tissue. Although most heart energy derives from fatty acids (FAs), excess lipid accumulation can cause cardiomyopathy. Similarly, high delivery of cholesterol can initiate coronary artery atherosclerosis. Hearts and arteries-unlike liver and adrenals-have nonfenestrated capillaries and lipid accumulation in both health and disease requires lipid movement from the circulation across the endothelial barrier. This review summarizes recent in vitro and in vivo findings on the importance of endothelial cell receptors and uptake pathways in regulating FAs and cholesterol uptake in normal physiology and cardiovascular disease. We highlight clinical and experimental data on the roles of ECs in lipid supply to tissues, heart, and arterial wall in particular, and how this affects organ metabolism and function. Models of FA uptake into ECs suggest that receptor-mediated uptake predominates at low FA concentrations, such as during fasting, whereas FA uptake during lipolysis of chylomicrons may involve paracellular movement. Similarly, in the setting of an intact arterial endothelial layer, recent and historic data support a role for receptor-mediated processes in the movement of lipoproteins into the subarterial space. We conclude with thoughts on the need to better understand endothelial lipid transfer for fuller comprehension of the pathophysiology of hyperlipidemia, and lipotoxic diseases such as some forms of cardiomyopathy and atherosclerosis.

Inhibition of Lipid Accumulation in Skeletal Muscle and Liver Cells: A Protective Mechanism of Bilirubin Against Diabetes Mellitus Type 2.

Ectopic lipid accumulation in skeletal muscle and liver drives the pathogenesis of diabetes mellitus type 2 (DMT2). Mild hyperbilirubinaemia has been repeatedly suggested to play a role in the prevention of DMT2 and is known for its capacity to shape an improved lipid phenotype in humans and in animals. To date, the effect of bilirubin on lipid accumulation in tissues that are prone to ectopic lipid deposition is unclear. Therefore, we analyzed the effect of bilirubin on lipid accumulation in skeletal muscle and liver cell lines. C2C12 skeletal mouse muscle and HepG2 human liver cells were treated with physiological concentrations of free fatty acids (FFA) (0.5 mM and 1 mM) and unconjugated bilirubin (UCB) (17.1 and 55 µM). The intracellular presence of UCB upon exogenous UCB administration was confirmed by HPLC and the lipid accumulation was assessed by using Nile red. Exposure of both cell lines to UCB significantly reduced lipid accumulation by up to 23% (p ≤ 0.001) in HepG2 and by up to 17% (p ≤ 0.01) in C2C12 cells at 0.5 and 5 h under hypoglycaemic conditions. Simultaneously, UCB slightly increased FFA uptake in HepG2 cells after 0.5 and 5 h and in C2C12 cells after 12 h as confirmed by gas chromatographic analyses of the remaining FFA content in the incubation media. The effects of UCB on lipid accumulation and uptake were abolished in the presence of higher glucose concentrations. Monitoring the uptake of a radiolabeled glucose analogue [18F]FDG: (2-deoxy-2-[18F]fluoro-D-glucose) into both cell types further indicated higher glucose consumption in the presence of UCB. In conclusion, our findings show that UCB considerably decreases lipid accumulation in skeletal muscle and liver cells within a short incubation time of max. 5 h which suggests that mildly elevated bilirubin levels could lower ectopic lipid deposition, a major key element in the pathogenesis of DMT2.

Effects and Mechanisms of Chitosan and ChitosanOligosaccharide on Hepatic Lipogenesis and Lipid Peroxidation, Adipose Lipolysis, and Intestinal Lipid Absorption in Rats with High-Fat Diet-Induced Obesity.

Chitosan and its derivative, chitosan oligosaccharide (CO), possess hypolipidemic and anti-obesity effects. However, it is still unclear if the mechanisms are different or similar between chitosan and CO. This study was designed to investigate and compare the effects of CO and high-molecular-weight chitosan (HC) on liver lipogenesis and lipid peroxidation, adipose lipolysis, and intestinal lipid absorption in high-fat (HF) diet-fed rats for 12 weeks. Rats were divided into four groups: normal control diet (NC), HF diet, HF diet+5% HC, and HF diet+5% CO. Both HC and CO supplementation could reduce liver lipid biosynthesis, but HC had a better effect than CO on improving liver lipid accumulation in HF diet-fed rats. The increased levels of triglyceride decreased lipolysis rate, and increased lipoprotein lipase activity in the perirenal adipose tissue of HF diet-fed rats could be significantly reversed by both HC and CO supplementation. HC, but not CO, supplementation promoted liver antioxidant enzymes glutathione peroxidase and superoxide dismutase activities and reduced liver lipid peroxidation. In the intestines, CO, but not HC, supplementation reduced lipid absorption by reducing the expression of fabp2 and fatp4 mRNA. These results suggest that HC and CO have different mechanisms for improving lipid metabolism in HF diet-fed rats.

Triclosan-induced abnormal expression of miR-30b regulates fto-mediated m6A methylation level to cause lipid metabolism disorder in zebrafish

Chronic exposure of triclosan (TCS) to zebrafish triggers high incidence of fatty liver and hepatitis; however, the underlying molecular mechanisms remain unclear. Herein, we identified miR-30b as a sensitive biomarker to TCS stress, reflecting in that its decreased expression caused metabolic toxicity, abnormal development and behavior, and lipid-metabolism disorder. By microinjecting the inhibitor and mimic experiments, miR-30b was proved to regulate lipid metabolism by its main target gene fto. Over-expression of FTO resulted in fat accumulation, elevation of the TG and TC levels and up-regulation of the PPARγ and CEBPα, as well as decrease of the global m6A level in larvae. On the contrary, the knock-down of FTO using MO caused the anti-lipogenic effect, decrease of the TG and T-CHO levels, and abnormal changes of cebpɑ, acsl5, fasn, ppap2c and pparγ etc. Further fortification tests of cycloleucine and betaine evidenced that the toxic effect was strongly dependent on regulation of the m6A level. The toxicity effects in the treatments of methylated donors and receptors were consistent with the changes in physiological functions of FTO knockdown and overexpression. The effects of cycloleucine on m6A level and lipid metabolism generally consisted with those of FTO, but this was not the case for betaine, reflecting in increased m6A level and lipid accumulation in larval liver. Consequently, we posit that TCS exposure caused zebrafish lipid-metabolism disorder by decreasing miR-30b expression to regulate fto-mediated m6A methylation level. These findings contribute to our deep understanding of the underlying molecular mechanisms regarding contaminant-originating fatty liver and hepatocellular carcinoma, and also have practical significance in pollution warning and target therapy for related diseases.

Ameliorative effects of functional crude-chalaza hydrolysates on the hepatosteatosis development induced by a high-fat diet

Approximately 400 metric tons of egg chalazae, a byproduct in the liquid-egg processing plant, are produced yearly but always regarded as a waste in Taiwan. Our team successfully developed a crude egg chalaza hydrolysate by protease-A digestion (CCH-A). Free branched-chain amino acids, 3-aminoisobutyric acid, and β-alanine, and anserine were assayed in the CCH-A used in this study. Besides, the in vitro bile-acid binding ability and inhibitory lipase activity of CCH-As were demonstrated. Then, high-fat diet feeding for 10 wk caused hyperlipidemia, insulin resistance, and hepatosteatosis in hamsters (P < 0.05). However, CCH-A co-treatment decreased serum/liver triglyceride levels and lipid accumulation in livers by increasing daily fecal lipid/bile-acid outputs, upregulating fatty-acid β oxidation, and downregulating fatty-acid biosynthesis in livers (P < 0.05). CCH-A co-treatment also amended insulin resistance, augmented hepatic antioxidant capacity, and decreased liver damages and inflammatory responses (P < 0.05). Taken together, our results do not only demonstrate the hepatoprotective effects of CCH-As against a chronic high-fat dietary habit, achieving effects similar to Simvastatin, but also decrease the environmental burden of handling chalazae in the liquid-egg industry.

Nuclear factor Y participates in alcoholic liver disease by activating SREBP1 expression in mice

Chronic and excessive alcohol consumption leads to alcoholic liver disease (ALD). However, the molecular mechanisms in the regulation of ALD have not been fully deciphered. Liver lipid accumulation is an important research direction in ALD. In this study, the physiological role of nuclear factor Y (NF–Y) in ALD and the related mechanisms were investigated using murine hepatocytes and an ethanol-induced liver injury mouse model. In this study, ethanol promoted hepatic NF–Y expression in a mouse model and Hepa1-6 mouse hepatocytes. Lentivirus-mediated NF–Y overexpression in Hepa1-6 cells markedly increased sterol regulatory element binding protein 1 (SREBP1) and fatty acid synthase (FASN) expression compared with empty vector control cells. Conversely, CRISPR/Cas9-mediated knockdown of NF–Y subunit A (NF-YA) attenuated FASN and SREBP1 expression. Mechanistically, luciferase reporter gene assays and chromatin immunoprecipitation (ChIP) analysis indicated that NF–Y activates the transcription of SREBP1 by directly binding to the CCAAT regulatory sequence motif in the promoter. Overall, our results reveal a previously unrecognized physiological function of NF–Y in ALD by activating sterol regulatory element-binding protein 1 (SREBP1). Modulation of hepatic NF–Y expression may therefore offer an attractive therapeutic approach to manage ALD.

Prkaa1 Metabolically Regulates Monocyte/Macrophage Recruitment and Viability in Diet-Induced Murine Metabolic Disorders.

Myeloid cells, including monocytes/macrophages, primarily rely on glucose and lipid metabolism to provide the energy and metabolites needed for their functions and survival. AMP-activated protein kinase (AMPK, its gene is PRKA for human, Prka for rodent) is a key metabolic sensor that regulates many metabolic pathways. We studied recruitment and viability of Prkaa1-deficient myeloid cells in mice and the phenotype of these mice in the context of cardio-metabolic diseases. We found that the deficiency of Prkaa1 in myeloid cells downregulated genes for glucose and lipid metabolism, compromised glucose and lipid metabolism of macrophages, and suppressed their recruitment to adipose, liver and arterial vessel walls. The viability of macrophages in the above tissues/organs was also decreased. These cellular alterations resulted in decreases in body weight, insulin resistance, and lipid accumulation in liver of mice fed with a high fat diet, and reduced the size of atherosclerotic lesions of mice fed with a Western diet. Our results indicate that AMPKα1/PRKAA1-regulated metabolism supports monocyte recruitment and macrophage viability, contributing to the development of diet-induced metabolic disorders including diabetes and atherosclerosis.

Diosmetin Ameliorates Nonalcoholic Steatohepatitis through Modulating Lipogenesis and Inflammatory Response in a STAT1/CXCL10-Dependent Manner

Nonalcoholic steatohepatitis (NASH) is an inflammatory lipotoxic disorder characterized by lipid accumulation and inflammation. Diosmetin (Dios), a flavonoid, has an active effect against nonalcoholic fatty liver disease, whereas its effect on NASH remains elusive. To investigate the effects of Dios on lipogenesis and inflammatory response and explore the molecular mechanisms of Dios on NASH, mice induced by high-fat diet (HFD), HepG2 cells stimulated by palmitic acid (PA), transcriptome sequencing, and molecular biological experiments were used. We show, by pathological analysis (HE, Oli Red O, and Masson staining) and biochemical parameters (TC, TG, LDL-C, ALT, and AST), Dios alleviated liver lipid accumulation and inflammatory injury. According to liver RNA-Seq analysis, CXCL10 and STAT1 were assumed to be the key target genes of Dios on NASH. Significantly, Dios regulated STAT1/CXCL10 signal pathway and further attenuated NASH via regulating the expression of LXRα/β, SREBP-1c, CHREBP, and NF-κB. In conclusion, Dios is proposed to alleviate NASH through suppression of lipogenesis and inflammatory response via a STAT1/CXCL10-dependent pathway.

A New Perspective on Fish Oil: The Prevention of Alcoholic Liver Disease.

The mechanisms of alcoholic liver diseases (ALD) are very complex and interrelated, including abnormal lipid metabolism, oxidative stress, and gut-derived endotoxin pathway. On the other hand, fish oil is rich in n-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which decrease blood triglyceride concentration in hypertriglycemia patients and show protective effects against fatty liver. However, there is limited evidence from studies of the relationship between fish oil and ALD based on the viewpoint of the intestinal integrity and microflora. Therefore, this review discusses the mechanism of amelioration for ALD by fish oil. Based on our previous studies, partial replacement of olive oil by fish oil in alcohol-containing liquid diet ameliorated the liver damage including fatty liver and inflammation in rats. Based on these results, the mechanisms of hepatoprotective effects due to fish oil substitution were discussed in three parts, such as regulating lipid metabolism, decreasing oxidative stress and maintaining intestinal health. First of all, we found that fish oil substitution increased plasma adiponectin levels, and then increasing MCAD and CPT-1 mRNA levels to accelerate fatty acid oxidation in liver, then further prevent ethanol-induced hepatosteatosis in rats with chronic alcohol-feeding. Fish oil replacement also enhanced hepatic autophagy flux, which enhanced lipid degradation, then inhibited lipid accumulation in liver. Secondly, the appreciable proportion of fish oil decreased lipid peroxidation by reducing the protein expression of cytochrome p450 2E1 in chronic alcohol-feeding rats. We also speculated that the appropriate proportion of n-6 and n-3 PUFAs is very important for preventing alcoholic liver disease. At last, substituting fish oil for olive oil normalized the intestinal permeability and fecal microbiota composition, thus providing a low plasma endotoxin level and inflammatory responses, which exert ameliorative effects on ethanol-induced liver injuries in rats.

Total Sesquiterpene Glycosides from Loquat Leaves Ameliorate HFD-Induced Insulin Resistance by Modulating IRS-1/GLUT4, TRPV1, and SIRT6/Nrf2 Signaling Pathways.

Loquat (Eriobotrya japonica Lindl.), a subtropical fruit tree native to Asia, is not only known to be nutritive but also beneficial for the treatment of diabetes in the south of China. To expand its development, this study was undertaken concerning the potential therapeutic role of total sesquiterpene glycosides (TSGs) from loquat leaves in insulin resistance (IR), the major causative factor of type 2 diabetes mellitus (T2DM). Male C57BL/6 mice were fed on high-fat diet (HFD) to induce IR and then were given TSG by oral administration at 25 and 100 mg/kg/day, respectively. TSG notably improved metabolic parameters including body weight, serum glucose, and insulin levels and prevented hepatic injury. Moreover, inflammatory response and oxidative stress were found to be remarkably alleviated in IR mice with TSG supplement. Further research in liver of IR mice demonstrated that TSG repaired the signalings of insulin receptor substrate-1 (IRS-1)/glucose transporter member 4 (GLUT4) and AMP-activated protein kinase (AMPK), which improved glucose and lipid metabolism and prevented lipid accumulation in liver. It was also observed that TSG suppressed the expression of transient receptor potential vanilloid 1 (TRPV1), whereas the signaling pathway of sirtuin-6 (SIRT6)/nuclear factor erythroid 2-related factor 2 (Nrf2) was significantly promoted. Based on the results, the current study demonstrated that TSG from loquat leaves potentially ameliorated IR in vivo by enhancing IRS-1/GLUT4 signaling and AMPK activation and modulating TRPV1 and SIRT6/Nrf2 signaling pathways.

Functional milk fat enriched in conjugated linoleic acid prevented liver lipid accumulation induced by a high-fat diet in male rats.

The aim was to investigate the potential effect of functional milk fat (FMF), naturally enriched in conjugated linoleic acid, on the prevention of liver lipid accumulation and some biochemical mechanisms involved in the liver triacylglycerol (TAG) regulation in high-fat (HF) fed rats. Male Wistar rats were fed (60 days) with S7 (soybean oil, 7%) or HF diets: S30 (soybean oil, 30%), MF30 (soybean oil, 3% + milk fat -MF-, 27%) or FMF30 (soybean oil, 3% + FMF, 27%). Nutritional parameters, hepatic fatty acid (FA) composition, liver and serum TAG levels, hepatic TAG secretion rate (TAG-SR), lipoprotein lipase (LPL) activity in adipose tissue and muscle, activities and/or mRNA levels of lipogenic and β-oxidative enzymes, and mRNA levels of transcription factors and FA transport proteins were assessed. The hepatic lipid accumulation induced by the S30 diet was associated with increased mRNA levels of FA transporters; and it was prevented by FMF through an increase in the hepatic TAG-SR, carnitine palmitoyltransferase-1a activity and peroxisome proliferator-activated receptor alpha mRNA levels, as well as by a reduction of the mRNA levels of FA transporters. The hypotriacylglyceridaemia observed in S30 was related with an increased LPL activity in adipose tissue and it was reverted by FMF through the increased hepatic TAG-SR. In brief, FMF prevented the liver lipid accumulation induced by HF diets by increasing the hepatic TAG-SR and β-oxidation, and reducing the hepatic FA uptake. The increased hepatic TAG-SR induced by FMF could be responsible for the attenuation of serum TAG alterations.

Lactobacillus plantarum KLDS1.0344 and Lactobacillus acidophilus KLDS1.0901 Mixture Prevents Chronic Alcoholic Liver Injury in Mice by Protecting the Intestinal Barrier and Regulating Gut Microbiota and Liver-Related Pathways.

Health and wellbeing are significantly impaired by alcoholic liver disease (ALD), and although some lactic acid bacteria strains have been shown previously to relieve ALD symptoms, the mechanisms behind these effects are still unclear. Here, the Lieber-DeCarli liquid diet containing alcohol was fed to C57BL/6J mice for 6 weeks to build a chronic alcoholic liver lesion model to study the protective effects and possible mechanisms of Lactobacillus mixture (Lactobacillus plantarum KLDS1.0344 and Lactobacillus acidophilus KLDS1.0901). The results showed that Lactobacillus mixture improved intestinal epithelial permeability and reduced the serum lipopolysaccharide (LPS) levels. Furthermore, Lactobacillus mixture inhibited liver lipid accumulation, oxidative stress, and inflammation by regulating AMPK, Nrf-2, and TLR4/NF-κB pathways. Importantly, the Lactobacillus mixture modulated the gut microbiota, resulting in increased short-chain fatty acid (SCFA) producers and decreased Gram-negative bacteria. Taken together, these findings indicated that the Lactobacillus mixture could positively regulate the gut microbiota, causing increased levels of SCFAs, which inhibited alcohol-induced liver lipid accumulation and oxidative stress through the gut-liver axis. Moreover, following administration of the Lactobacillus mixture, the improvement of intestinal epithelial permeability and the reduction of Gram-negative bacteria led to the decrease of LPS entering the portal vein, thereby inhibiting alcohol-induced liver inflammation.

The novel liver X receptor beta agonist, ouabagenin, prevent arterial lipid deposition in SHRSP5/Dmcr rat

Background and Aims: Liver X Receptor (LXR) is very important target for drug discovery because it can remove cholesterol from atheroma. However, LXR induces a fatty liver as a side effect. LXR has 2 subtypes, LXRα aggravates lipid-accumulation in liver, whereas LXRβ removes the cholesterol. However, specific LXRβ agonist has not discovered. We focused on Ouabagenin (OBG) as the specific LXRβ agonist, and demonstrated the effect of OBG using SHRSP5/Dmcr rat (SHRSP5) which induces nonalcoholic steatohepatitis (NASH) and cardiovascular disease (CVD).

Liver Lipid Accumulation in European Bullhead (Cottus cobio) from a High-Mountain Lake: An Adaptive Strategy to Survive the Adverse Winter Season

The hypothesis that liver lipid accumulation in fish is an adaptive strategy to survive the winter in the high-altitude environment was assessed in this study. During summer 2019, specimens of Cottus gobio were sampled in 15 watercourses of Friuli Venezia-Giulia Region (Italy) to verify if hepatic steatosis is or not normally present in the species. To do this, hepatic vacuolization was assessed by histology using a semiquantitative score. Furthermore, C. gobio were also captured during the ice-free season at Dimon Lake (1872 m a.s.l.) and But Stream (520 m a.s.l.) to compare the trend in lipid accumulation: water temperature, hepatosomatic index (HSI), gonadosomatic index (GSI), Fulton’s condition factor (K), and lipid area percentage (lipid %) were measured monthly. Findings revealed that liver steatosis is rather common in C. gobio. However, the trend in lipid accumulation of this species differed between Dimon Lake and But Stream. Based on the HSI and the GSI, the reproductive cycles differed in fish from the two environments (April–May in But Stream; May–June in Dimon Lake). While K values remained unchanged in the But Stream specimens, significant changes were recorded for Dimon specimens. The increase in lipid % from July to August in the Dimon Lake specimens coincided with greater food availability. With the rapid drop in lake water temperature in October, the lipid % decreased due to slower metabolic rate and lipid utilization from liver stores. There was a slight decrease in lipid % in the But Stream specimens, indicating that lipids were not being accumulated. Introduced years ago, the Dimon Lake bullhead population has since adapted to the winter conditions at high elevation.

Naringin Attenuates High Fat Diet Induced Non-alcoholic Fatty Liver Disease and Gut Bacterial Dysbiosis in Mice.

The incidence of non-alcoholic fatty liver disease (NAFLD) is rising annually, and emerging evidence suggests that the gut bacteria plays a causal role in NAFLD. Naringin, a natural flavanone enriched in citrus fruits, is reported to reduce hepatic lipid accumulation, but to date, no investigations have examined whether the benefits of naringin are associated with the gut bacteria. Thus, we investigated whether the antilipidemic effects of naringin are related to modulating the gut bacteria and metabolic functions. In this study, C57BL/6J mice were fed a high-fat diet (HFD) for 8 weeks, then fed an HFD with or without naringin administration for another 8 weeks. Naringin intervention reduced the body weight gain, liver lipid accumulation, and lipogenesis and attenuated plasma biochemical parameters in HFD-fed mice. Gut bacteria analysis showed that naringin altered the community compositional structure of the gut bacteria characterized by increased benefits and fewer harmful bacteria. Additionally, Spearman’s correlation analysis showed that at the genus level, Allobaculum, Alloprevotella, Butyricicoccus, Lachnospiraceae_NK4A136_group, Parasutterella and uncultured_bacterium_f_Muribaculaceae were negatively correlated and Campylobacter, Coriobacteriaceae_UCG-002, Faecalibaculum and Fusobacterium were positively correlated with serum lipid levels. These results strongly suggest that naringin may be used as a potential agent to prevent gut dysbiosis and alleviate NAFLD.

Dendrobium Officinale Polysaccharide Attenuates Insulin Resistance and Abnormal Lipid Metabolism in Obese Mice

Objectives: Dendrobium officinale polysaccharide (DOP), a traditional Chinese medicine, has several pharmacological actions in hepatoprotection, cancer chemotherapy, hypoglycemia, anti-fatigue effect, and gastric ulcer protection, among others. However, the effect of DOP in obesity-associated insulin resistance and lipid metabolism remains unknown. This study aimed to investigate the role of DOP in insulin resistance and abnormal lipid metabolism in obese mice. Materials and Methods: The insulin resistance models were established using 3T3-L1 adipocytes, C2C12 myocytes, and primary cultured hepatocytes incubated in palmitate acid. After treatment with DOP, insulin-stimulated glucose uptake of 3T3-L1 adipocytes and C2C12 myocytes and glucose output of primary cultured hepatocytes were detected. In addition, the insulin-stimulated phosphorylation of AKT was confirmed by western blot. Related mechanism studies were confirmed by qRT-PCR and western blotting. DOP was orally administrated in obese mice. Fasting blood glucose, fasting serum insulin, glucose tolerance test (GTT), and insulin tolerance test (ITT) were measured to evaluate insulin sensitivity of mice. Lipid analysis was conducted to evaluate the effect of DOP on lipid metabolism in obese mice. Results: In vitro, DOP treatment ameliorated palmitic acid-induced insulin resistance in adipocytes, myocytes, and hepatocytes. Mechanistically, DOP regulated cellular insulin sensitivity via peroxisome proliferator-activated receptor-γ (PPAR-γ). Furthermore,administration of DOP significantly reduced the insulin resistance of obese mice, as seen by decreased levels of fasting glucose, fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR). In addition, DOP treatment attenuated high fat diet(HFD)-induced liver lipid accumulation by reducing liver triglycerides (TG), plasma free fatty acid (FFA), serum cholesterol (TC), TG, and low-density lipoprotein cholesterol (LDL-C) levels, and increasing HDL-C levels. Conclusions: DOP could improve obesity-associated insulin resistance and abnormal lipid metabolism by acting on PPAR-γ, which may serve as a potential therapeutic agent for obesity-associated insulin resistance and lipid metabolism disorder. Funding Statement: This work was supported by the Natural Science Foundation of Hunan Province (2020JJ4799). Declaration of Interests: There are no potential conflicts of interest to declare. Ethics Approval Statement: All protocols of animal care and experiment were reviewed and approved by the Institutional Animal Care and Use Committee of the Laboratory Animal Research Center at Xiangya Medical School of Central South University, China.

The nuclear and cytoplasmic roles of miR-320 in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder worldwide. Multiple metabolic disorders, such as hyperlipidemia, hyperglycemia, insulin resistance and obesity, have been reportedly associated with NAFLD, but little is known about the detailed mechanisms. Here, we explored the effects of multiple metabolic disorders, especially hyperglycemia on lipid accumulation in liver using several well-established animal models. We found that liver lipid deposition was increased in both type 1 diabetes and high-fat diet (HFD) induced hyperlipidemia models, suggesting that either hyperglycemia or hyperlipidemia alone or together was able to trigger NAFLD. Moreover, we tested whether miR-320, a miRNA promoting lipid accumulation in heart revealed by our previous study, also participated in NAFLD. Though miR-320 treatment further increased liver lipid deposition in type 1 diabetes and HFD-feeding mice, it showed no effect in leptin-receptor deficient db/db mice. Interestingly, miR-320 affected different target genes in cytosol and nucleus, respectively, which collectively led to liver lipid overload. Our findings illustrated the complex roles of miRNAs in subcellular fractions including nucleus and cytoplasm, which may lead to new insights into the mechanisms and treatment strategies for NAFLD in the future.