Liver Lipid Metabolism Research Articles

MC-LR Aggravates Liver Lipid Metabolism Disorders in Obese Mice Fed a High-Fat Diet via PI3K/AKT/mTOR/SREBP1 Signaling Pathway.

Obesity, a metabolic disease caused by excessive fat accumulation in the body, has attracted worldwide attention. Microcystin-LR (MC-LR) is a hepatotoxic cyanotoxin which has been reportedly to cause lipid metabolism disorder. In this study, C57BL/6J mice were fed a high-fat diet (HFD) for eight weeks to build obese an animal model, and subsequently, the obese mice were fed MC-LR for another eight weeks, and we aimed to determine how MC-LR exposure affects the liver lipid metabolism in high-fat-diet-induced obese mice. The results show that MC-LR increased the obese mice serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), indicating damaged liver function. The lipid parameters include serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and liver TG, which were all increased, whilst the high-density lipoprotein cholesterol (HDL-c) was decreased. Furthermore, after MC-LR treatment, histopathological observation revealed that the number of red lipid droplets increased, and that steatosis was more severe in the obese mice. In addition, the lipid synthesis-related genes were increased and the fatty acid β-oxidation-related genes were decreased in the obese mice after MC-LR exposure. Meanwhile, the protein expression levels of phosphorylation phosphatidylinositol 3-kinase (p-PI3K), phosphorylation protein kinase B (p-AKT), phosphorylation mammalian target of rapamycin (p-mTOR), and sterol regulatory element binding protein 1c (SREBP1-c) were increased; similarly, the p-PI3K/PI3K, p-AKT/AKT, p-mTOR/mTOR, and SREBP1/β-actin were significantly up-regulated in obese mice after being exposed to MC-LR, and the activated PI3K/AKT/mTOR/SREBP1 signaling pathway. In addition, MC-LR exposure reduced the activity of superoxide dismutase (SOD) and increased the level of malondialdehyde (MDA) in the obese mice's serum. In summary, the MC-LR could aggravate the HFD-induced obese mice liver lipid metabolism disorder by activating the PI3K/AKT/mTOR/SREBP1 signaling pathway to hepatocytes, increasing the SREBP1-c-regulated key enzymes for lipid synthesis, and blocking fatty acid β-oxidation.

Protein Targeting to Glycogen (PTG): A Promising Player in Glucose and Lipid Metabolism.

Protein phosphorylation and dephosphorylation are widely considered to be the key regulatory factors of cell function, and are often referred to as "molecular switches" in the regulation of cell metabolic processes. A large number of studies have shown that the phosphorylation/dephosphorylation of related signal molecules plays a key role in the regulation of liver glucose and lipid metabolism. As a new therapeutic strategy for metabolic diseases, the potential of using inhibitor-based therapies to fight diabetes has gained scientific momentum. PTG, a protein phosphatase, also known as glycogen targeting protein, is a member of the protein phosphatase 1 (PP1) family. It can play a role by catalyzing the dephosphorylation of phosphorylated protein molecules, especially regulating many aspects of glucose and lipid metabolism. In this review, we briefly summarize the role of PTG in glucose and lipid metabolism, and update its role in metabolic regulation, with special attention to glucose homeostasis and lipid metabolism.

Loss of Hepatic Leucine-Rich Repeat-Containing G-Protein Coupled Receptors 4 and 5 Promotes Nonalcoholic Fatty Liver Disease

The roof plate-specific spondin-leucine-rich repeat-containing G-protein-coupled receptor 4/5 (Lgr4/5)-zinc and ring finger 3/ring finger protein 43 module is a master regulator of hepatic Wnt/β-catenin signaling and metabolic zonation, but its impact on nonalcoholic fatty liver disease (NAFLD) remains unclear. We studied whether hepatic epithelial cell-specific loss of the Wnt/β-catenin modulator Lgr4/5 promoted NAFLD. The 3- and 6-month-old mice with hepatic epithelial cell-specific deletion of both receptors Lgr4/5 (Lgr4/5dLKO) were compared with control mice on feeding with normal diet or high-fat diet (HFD). Livers of 6-month-old HFD-fed Lgr4/5dLKO mice developed hepatic steatosis and fibrosis compared with control mice. Serum cholesterol-high-density lipoprotein and total cholesterol levels in 3- and 6-month-old HFD-fed Lgr4/5dLKO mice were decreased compared with control mice. An exvivo primary hepatocyte culture assay and a comprehensive BA characterization in liver, plasma, bile, and feces demonstrated that normal diet-fed Lgr4/5dLKO mice revealed impaired BA secretion, predisposing to develop cholestatic characteristics. Lipidome and RNA-sequencing analyses demonstrated severe alterations in several lipid species and pathways controlling lipid metabolism in livers of Lgr4/5dLKO mice. In conclusion, loss of hepatic Wnt/β-catenin activity by Lgr4/5 deletion led to loss of BA secretion, cholestatic features, altered lipid homeostasis, and deregulation of lipoprotein pathways. Both BA and intrinsic lipid alterations contributed to the onset of NAFLD.

Coiled-coil domain containing 3 suppresses breast cancer growth by protecting p53 from proteasome-mediated degradation.

Coiled-coil domain containing 3 (CCDC3) was previously shown to regulate liver lipid metabolism as a secretory protein. Here, we report an unexpected intracellular role of CCDC3 as a tumor suppressor in breast cancer (BrC). Bioinformatics datasets analysis showed that CCDC3 is under-expressed in BrCs, while its higher levels are correlated with higher overall survival and lower relapse of cancer patients, and CCDC3 is positively correlated with p53 and its target genes. Ectopic CCDC3 markedly suppressed proliferation, colony formation, and xenograft tumor growth by augmenting p53 activity in BrC cells. Depletion of endogenous CCDC3 by CRISPR-Cas9 increased proliferation and drug resistance of BrC cells by alleviating 5-Fluorouracil (5-FU)-induced p53 level and activity. Mechanistically, CCDC3 bound to the C-termini of p53 and MDM2, consequently stabilizing p53 in the nucleus and impairing MDM2 recruitment of p53 to the 26S proteosome without inhibiting p53 ubiquitination. p53 induced CCDC3 expression by binding to its promoter in BrC cells. Our results unveil a unique mechanism underlying CCDC3 activation of p53 in a positive feedback fashion to suppress BrC growth.

MLN4924 Treatment Diminishes Excessive Lipid Storage in High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease (NAFLD) by Stimulating Hepatic Mitochondrial Fatty Acid Oxidation and Lipid Metabolites.

MLN4924 is a selective neddylation inhibitor that has shown great potential in treating several cancer and metabolic diseases, including obesity. However, it remains largely unknown whether MLN4924 has similar effect on non-alcoholic liver disease (NAFLD), which is closely associated with metabolic disorders. Here, we investigated the role of MLN4924 in NAFLD treatment and the underlying mechanism of the action using primary hepatocytes stimulated with free fatty acid, as well as high-fat diet (HFD)-induced NAFLD mouse models. We found that MLN4924 can inhibit the accumulation of lipid and reduce the expression of peroxisome proliferator-activated receptor γ (PPARγ), a key player in adipocyte differentiation and function in both in vivo and in vitro models. Moreover, we verified its important role in decreasing the synthesis and accumulation of fat in the liver, thus mitigating the development of NAFLD in the mouse model. The body weight and fat mass in MLN4924-treated animals were significantly reduced compared to the control group, while the metabolic activity, including O2 consumption, CO2 and heat production, also increased in these animals. Importantly, we demonstrated for the first time that MLN4924 can markedly boost mitochondrial fat acid oxidation (FAO) to alter liver lipid metabolism. Finally, we compared the metabolites between MLN4924-treated and untreated Huh7 cells after fatty acid induction using lipidomics methods and techniques. We found induction of several metabolites in the treated cells, including Beta-guanidinopropionic acid (b-GPA) and Fluphenazine, which was in accordance with the increase of FAO and metabolism. Together, our study provided a link between neddylation modification and energy metabolism, as well as evidence for targeting neddylation as an emerging therapeutic approach to tackle NAFLD.

Salidroside in the Treatment of NAFLD/NASH.

Non-alcoholic fatty liver disease (NAFLD) is the commonest reason for chronic liver diseases in the world and is commonly related to the hepatic manifestation of the metabolic syndrome. Non-alcoholic steatohepatitis (NASH) is a deteriorating form of NAFLD, which can eventually develop into fibrosis, cirrhosis, and liver cancer. The reason for NAFLD/NASH development is complicated, such as liver lipid metabolism, oxidative stress, inflammatory response, apoptosis and autophagy, liver fibrosis and gut microbiota. Apart from bariatric surgery and lifestyle changes, officially approved drug therapy for NAFLD/NASH treatment is lacking. Salidroside (SDS) is a phenolic compound extensively distributed in the tubers of Rhodiola plants, which possesses many significant biological activities. This review summarized the related targets regulated by SDS in treating NAFLD/NASH. It is indicated that SDS could improve the status of NAFLD/NASH by ameliorating abnormal lipid metabolism, inhibiting oxidative stress, regulating apoptosis and autophagy, reducing inflammatory response, alleviating fibrosis and regulating gut microbiota. In conclusion, although the multiple bioactivities of SDS have been confirmed, the clinical data are inadequate and need to become the focus of attention in the later study.

Dietary supplementation with Tolypocladium sinense mycelium prevents dyslipidemia inflammation in high fat diet mice by modulation of gut microbiota in mice.

Obesity is a risk factor for many serious health problems, associated with inflammation, hyperlipidemia, and gut dysbiosis. Prevention of obesity is especially important for human health. Tolypocladium sinense is one of the fungi isolated from Chinese caterpillar fungus, which is a traditional Chinese medicine with putative gut microbiota modulation effects. Here, we established a high-fat diet (HFD)-induced hyperlipidemia mice model, which was supplemented with lyophilized T. sinense mycelium (TSP) daily to evaluate its anti-obesity effects. The results indicated that TSP supplementation can effectively alleviate the inflammatory response and oxidative stress levels caused by obesity. TSP significantly prevented obesity and suppressed dyslipidemia by regulating the expression of lipid metabolism genes in the liver. TSP is also effective in preventing the HFD-induced decline in short-chain fatty acid (SCFA) content. Gut microbiota profiling showed that TSP supplementation reversed HFD diet-induced bacterial abundance and also altered the metabolic pathways of functional microorganisms, as revealed by KEGG analysis. It is noteworthy that, correlation analysis reveals the up-regulated gut microbiota (Lactobacillus and Prevotella_9) are closely correlated with lipid metabolism parameters, gene expression of liver lipid metabolism and inflammatory. Additionally, the role of TSP in the regulation of lipid metabolism was reconfirmed by fecal microbiota transplantation. To sum up, our results provide the evidence that TSP may be used as prebiotic agents to prevent obesity by altering the gut microbiota, alleviating the inflammatory response and regulating gene expression of liver lipid metabolism.

Therapeutic Effect of Curcumin on 5/6Nx Hypertriglyceridemia: Association with the Improvement of Renal Mitochondrial β-Oxidation and Lipid Metabolism in Kidney and Liver

Chronic kidney disease (CKD) prevalence is constantly increasing, and dyslipidemia in this disease is characteristic, favoring cardiovascular events. However, the mechanisms of CKD dyslipidemia are not fully understood. The use of curcumin (CUR) in CKD models such as 5/6 nephrectomy (5/6Nx) has shown multiple beneficial effects, so it has been proposed to correct dyslipidemia without side effects. This work aimed to characterize CUR's potential therapeutic effect on dyslipidemia and alterations in lipid metabolism and mitochondrial ß-oxidation in the liver and kidney in 5/6Nx. Male Wistar rats were subjected to 5/6Nx and progressed by 4 weeks; meanwhile, CUR (120 mg/kg) was administered for weeks 5 to 8. Our results showed that CUR reversed the increase in liver and kidney damage and hypertriglyceridemia induced by 5/6Nx. CUR also reversed mitochondrial membrane depolarization and β-oxidation disorders in the kidney and the increased lipid uptake and the high levels of proteins involved in fatty acid synthesis in the liver and kidney. CUR also decreased lipogenesis and increased mitochondrial biogenesis markers in the liver. Therefore, we concluded that the therapeutic effect of curcumin on 5/6Nx hypertriglyceridemia is associated with the restoration of renal mitochondrial ß-oxidation and the reduction in lipid synthesis and uptake in the kidneys and liver.

Taurine improves health of juvenile rice field eel (Monopterus albus) fed with oxidized fish oil: Involvement of lipid metabolism, antioxidant capacity, inflammatory response

An 8-weeks feeding experiment was performed to evaluate the potential effect of dietary taurine on the growth, liver oxidative stress and lipid metabolism, intestinal integrity and inflammatory response as well as the skin pigments of Monopterus albus fed with the oxidized fish oil diet. With that purpose, four iso-nitrogenous and iso-lipid experimental diets were formulated, including FO (2% fresh fish oil), OO (2% oxidized fish oil completely replacing the fresh fish oil in FO group) supplemented with 0%, 0.2% (OOT0.2) and 0.5% (OOT0.5) taurine. Each diet was randomly fed to triplicate groups of 50 fish (average initial weight 30.09 ± 0.06 g). The results showed that long-term feeding of OO diet did not affect the growth performance, while decreased the contents of serum immune parameters, lowered the liver antioxidative enzymes activities and induced oxidative stress, caused abnormal fat deposition in liver by interfering lipid metabolism-related genes mRNA express profile, simultaneously accompanied by hepatocyte atrophy, destroyed the intestinal mucosal barrier through dysregulation of the mRNA expression of tight junction proteins and raised the inflammatory response by elevating the pro-inflammatory cytokines mRNA abundance, and generated undesirable skin hyperpigmentation via boosting tyrosinase activity. Notably, taurine administration improved the growth performance and partially mitigated the negative impacts in M. albus subjected to the oxidized fish oil. Taken together, it was supposed that taurine exerted its anti-oxidative and anti-inflammatory properties to confer protection against oxidized fish oil. These findings would provide a theoretical basis for the application of taurine in aquatic feed.

Effects of supplemental glycerol monolaurate on growth, hepatic lipid metabolism, antioxidant capacity and mitochondrial function of large yellow croaker (Larimichthys crocea) fed diets with high soybean oil level

The present study was conducted to investigate the effect of supplemental glycerol monolaurate (GML) on growth performance, hepatic lipid metabolism, antioxidant capacity and mitochondrial function in large yellow croaker (Larimichthys crocea) fed diets with high soybean oil (SBO) level. The trial diet with 7% fish oil (FO) was designed as the negative control while the diet with 7% SBO was designed as the positive control. The other three diets were formulated with the administration of 400, 800 and 1600 mg/kg GML (0.04%, 0.08% and 0.16%) on basis of the positive control diet. Results showed that the specific growth rate (SGR) was increased and the feed conversion ratio (FCR) was decreased significantly in fish fed diets with GML supplementation compared with the positive control diet, while no difference was observed in the survival rate (SR) among dietary treatments. Fish fed the diet with 0.04% GML supplementation had significantly lower triglycerides and total cholesterol contents compared with those in the positive control group. The mRNA expression of lipogenesis-related genes (srebp1c and acc) were down-regulated while the mRNA expression of lipolysis and fatty acid β-oxidation-related genes (atgl, pparα and cpt1) were up-regulated in fish fed diets with 0.04% and 0.08% GML. Compared with the positive control diet, fish fed diets with 0.04% and 0.08% GML supplementation exhibited remarkably higher activities of superoxide dismutase, catalase and the content of glutathione, as well as lower malondialdehyde level. Furthermore, in fish fed diets with 0.04% and 0.08% GML, the morphology of mitochondria was improved and their number was increased. The mRNA expression of genes related to mitochondrial biogenesis (pgc1-α, tfam and nrf1) were significantly increased in fish fed with 0.04% and 0.08% GML supplementation. Meanwhile, the content of triphosadenine (ATP), the activity of citrate synthase (CS) and succinate dehydrogenase (SDH) in liver were increased significantly in 0.04% and 0.08% treatments compared with the positive control group. Conclusively, these results indicated that dietary GML supplementation (0.04%–0.08%) could promote growth performance, improve liver lipid metabolism, antioxidant capacity and enhance mitochondrial function in large yellow croaker fed with the SBO based diet.

Probiotics for the improvement of metabolic profiles in patients with metabolic-associated fatty liver disease: A systematic review and meta-analysis of randomized controlled trials.

This meta-analysis of randomized controlled trials (RCTs) was conducted to assess the efficacy of probiotics in the treatment of metabolic-associated fatty liver disease (MAFLD) mainly in terms of liver function, glucose and lipid metabolism, and inflammation. RCTs were searched on PubMed, Web of Science, Embase, and the Cochrane Library until June 2022.A meta-analysis was performed on the therapeutic efficacy of probiotics on liver function, glucose and lipid metabolism, and inflammatory biomarkers by using RevMan 5.4 software. A total of 772 patients from 15 studies were included in the analysis. The methodological quality varied across studies. We found that adding probiotic therapies could reduce the levels of alanine aminotransferase [mean difference (MD): -11.76 (-16.06, -7.46), p<0.00001], aspartate aminotransferase (MD: -9.08 (-13.60, -4.56), p < 0.0001], γ-glutamyltransferase [MD: -5.67 (-6.80, -4.54), p<0.00001] and homeostasis model assessment-insulin resistance [MD: -0.62 (-1.08, -0.15), p = 0.01], in patients with MAFLD compared with those in control individuals. However, there was no statistically significant improvement in the levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, C-reactive protein and tumor necrosis factor α among patients with MAFLD. Subgroup analyses showed that other key factors, such as age, participants' baseline body mass index, and the duration of intervention, may influence probiotic therapy outcomes. There is promising evidence that probiotic supplementation can reduce liver enzyme levels and regulate glycometabolism in patients with MAFLD. Further rigorous and long-term trials exploring these novel therapeutic perspectives are warranted to confirm these results.

Cordyceps guangdongensis lipid-lowering formula alleviates fat and lipid accumulation by modulating gut microbiota and short-chain fatty acids in high-fat diet mice.

Obesity has caused serious health and economic problems in the world. Cordyceps guangdongensis is a high-value macrofungus with broad application potential in the food and bio-medicine industry. This current study aimed to estimate the role of C. guangdongensis lipid-lowering compound formula (CGLC) in regulating fat and lipid accumulation, gut microbiota balance, short-chain fatty acid (SCFA) contents, and expression levels of genes involved in fat and lipid metabolism in high-fat diet (HFD) mice. The results showed that CGLC intervention markedly reduced body weights and fat accumulation in HFD mice, improved glucose tolerance and blood lipid levels, and decreased lipid droplet accumulation and fat vacuole levels in the liver. CGLC decreased the ratio of Firmicutes and Bacteroidetes and increased the relative abundances of Bacteroides (B. acidifaciens) and Bifidobacterium (B. pseudolongum). In addition, CGLC treatment significantly promoted the production of SCFAs and regulated the relative expression levels of genes involved in fat and lipid metabolism in liver. Association analysis showed that several species of Bacteroides and most of SCFAs were significantly associated with serum lipid indicators. These results suggested that CGLC is a novel candidate formulation for treating obesity and non-alcohol fatty liver by regulating gut microbiota, SCFAs, and genes involved in fat and lipid metabolism.

ODP190 Efficacy of Esaxerenone on Hypertensive Patients with Type 2 Diabetes or Those with Impaired Glucose Tolerance

Abstract Patients with diabetes may develop mineralocorticoid receptor (MR) related hypertension due to abnormal activation of MR, thusMR blocker (MRB) is used for the treatment of hypertensionin patients with diabetes. Although theselective MRB esaxerenone (Esax)approved for hypertension, the effectiveness of Esax in daily clinical practice has not provenin hypertensive patients with type 2 diabetes (T2D) or those withimpaired glucose tolerance (IGT). The aim of this study is to clarifythe efficacy of Esax in these patients. In this retrospective study, patientswho initiated Esax from May 2019 to February 2020 and thosewho initiated amlodipine (Amlo) were screened. After excluding patients with a history of hypersensitivity to these drugs, K &amp;gt; 5. 0 mEq/L at the baseline and severe renal dysfunction (eGFR &amp;lt; 30 mL/min/1.73m 2), and patients receiving potassium preparations, 35 and 70 patients were enrolled in the Esax and Amlo group, respectively. After propensity score matching with the parameters including gender, age, body mass index (BMI), concomitant use of angiotensin receptor blocker, systolic blood pressure (SBP), diastolic blood pressure (DBP), K, AST, ALT, TG and eGFR, finally each 24 cases were analyzed. Primary endpoints were changes (Δ) in SBP and DBP from the baseline to 6 months after the initiation of the drugs. Secondary endpoints comprised changes in liver enzymes and those in lipid metabolism markers. Unpaired t-test was used for statistical analysis. The dose of Esax and Amlo were 2.2±0.5 mg and 4.1±1.2 mg at the baseline, and 3.4±1.3 mg and 5.3±1.2 mg at 6 months, respectively. SBP was more decreased in the Esax group compared with the Amlo group (ΔSBP: -27± 20 mmHg vs -11± 14 mmHg, p&amp;lt;0. 05). DBP was not significantly different between the two groups (ΔDBP: -11± 10 mmHg vs -9± 14 mmHg). In the Esax group, ALT and TG were significantly decreased (ΔAST: -7.3 ± 11.5 U/L vs +0.9 ± 9.5 U/L, p&amp;lt;0. 05,ΔTG: -14.3 ± 51. 0 mg/dL vs +33.5 ± 59.4 mg/dL, p&amp;lt;0. 05), and HDL-C significantlyincreased (ΔHDL: +1.8 ± 6.1 mg/dL vs -3.8 ± 4.8 mg/dL, p&amp;lt;0. 05). Severeadverse events were not observed in any subjects. These results suggest the efficacy of Esax for controlling blood pressure as well as the plausible benefit in liver disease and lipid metabolism in hypertensive patients with T2D or IGT. Presentation: No date and time listed

Discovery of a structurally novel, potent, and once-weekly free fatty acid receptor 1 agonist for the treatment of diabetes

Type 2 diabetes mellitus (T2DM) is a lifelong disease that requires long-term medication to control glucose levels, and thereby long-acting drug has been clinically needed for improving medical adherence. The free fatty acid receptor 1 (FFA1) was considered as a promising target for several diseases, such as T2DM, pain and fatty liver. However, no once-weekly FFA1 agonist has been reported until now. Herein, we report the successful discovery of ZLY50, the first once-weekly FFA1 agonist with a completely new chemotype, highly agonistic activity and selectivity on FFA1. Moreover, ZLY50 has enough brain exposure to activate FFA1 in brain, and it is the first orally available FFA1 agonist with analgesic activity. Notably, the long-term anti-diabetic and anti-fatty liver effects of ZLY50 (once-weekly) were better than those of HWL-088 (once-daily), a highly potent FFA1 agonist with far stronger glucose-lowering effect than Phase 3 clinical candidate TAK-875. Further mechanism studies suggested that ZLY50 alleviates fatty liver by regulating the expressions of genes related to lipid metabolism, mitochondrial function, and oxidative stress in liver.

Potential Mechanisms of Gut-Derived Extracellular Vesicle Participation in Glucose and Lipid Homeostasis.

The intestine participates in the regulation of glucose and lipid metabolism in multiple facets. It is the major site of nutrient digestion and absorption, provides the interface as well as docking locus for gut microbiota, and harbors hormone-producing cells scattered throughout the gut epithelium. Intestinal extracellular vesicles are known to influence the local immune response, whereas their roles in glucose and lipid homeostasis have barely been explored. Hence, this current review summarizes the latest knowledge of cargo substances detected in intestinal extracellular vesicles, and connects these molecules with the fine-tuning regulation of glucose and lipid metabolism in liver, muscle, pancreas, and adipose tissue.

Chiliadenus iphionoides Reduces Body Weight and Improves Parameters Related to Hepatic Lipid and Glucose Metabolism in a High-Fat-Diet-Induced Mice Model of NAFLD.

Non-alcoholic fatty liver disease (NAFLD) has become an epidemic with increasing prevalence. Limited treatment options and poor adherence emphasize the urgent need for novel therapies for the treatment and/or prevention of NAFLD. Bioactive natural compounds found in medicinal plants are promising as novel therapeutic agents for NAFLD. Chiliadenus iphionoides, a medicinal plant with several health-promoting properties, is an encouraging candidate. The current study aimed to elucidate the metabolic effects of C. iphionoides consumption in a high-fat-diet (HFD)-induced model of NAFLD. Male C57BL/6J mice (n = 40, 7-8-week-old) were fed a HFD (60% fat) with/without 0.5 or 2.5 gr C. iphionoides for fifteen weeks. Diet supplementation with C. iphionoides significantly ameliorated HFD-induced weight gain. Likewise, liver and adipose tissue weights were profoundly lower in the C. iphionoides-fed groups. Reduced liver steatosis in those groups was corroborated by histology, plasma liver enzyme levels, and lipid profile, indicating improved liver function and lipid metabolism in addition to enhanced insulin sensitivity. The addition of C. iphionoides to an obesogeneic diet can beneficially alleviate metabolic alterations and may be a practicable strategy for the management of NAFLD.

Modification of the diabetes prevention program for the treatment of nonalcoholic fatty liver disease: A pilot study.

The Diabetes Prevention Program (DPP) is the gold standard lifestyle modification program that reduces incident type 2 diabetes mellitus. Patients with prediabetes and patients with non-alcoholic fatty liver disease (NAFLD) often share metabolic features; we hypothesized that the DPP could be adapted and used to improve outcomes in patients with NAFLD. NAFLD patients were recruited into a 1year modified DPP. Demographics, medical comorbidities, and clinical laboratory values were collected at baseline, 6 and 12months. The primary endpoint was change in weight at 12months. Secondary endpoints were changes in hepatic steatosis, metabolic comorbidities, and liver enzymes (per-protocol basis) and retention at 6 and 12months. Fourteen NAFLD patients enrolled; three dropped out before 6months. From baseline to 12months, hepatic steatosis (p=0.03), alanine aminotransferase (p=0.02), aspartate aminotransferase (p= 0.02), high-density lipoprotein (p=0.01) and NAFLD fibrosis score (p<0.001) improved, but low-density lipoprotein worsened (p=0.04). Seventy-nine percent of patients completed the modified DPP. Patients lost weight and had improvements in five out of six indicators of liver injury and lipid metabolism. NCT04988204.

Effects of Coix Seed Oil on High Fat Diet-Induced Obesity and Dyslipidemia.

Dietary intervention is becoming more popular as a way to improve lipid metabolism and reduce the prevalence of diet-related chronic disorders. We evaluated the effects of several dietary oils on body weight, fat mass, liver weight, and tumor necrosis factor in obese mice given a high-fat diet (HFD) to discover if coix seed oil (CSO) had an anti-obesity impact. As compared to other dietary fats, CSO treatment considerably lowered body weight and liver index, successfully sup-pressed total cholesterol and triglyceride content, and raised liver lipid deposition and lipid metabolism problem induced by high fat intake. Furthermore, gas chromatography research revealed that CSO extracted by supercritical fluid, with 64% being CSO extracted by supercritical fluid, and the greatest amounts of capric acids and lauric acids being 35.28% and 22.21%, respectively. CSO contained a high content of medium-chain fatty acids and was able to modify hepatic fatty acid metabolism and lipid levels in HFD-induced obese mice. According to the results, CSO has the potential to replace dietary lipids as a promising functional lipid in the prevention of met-abolish disorders.

Effect of n-6/n-3 PUFA ratio on body fat deposition, tissues fatty acid composition and key genes expression of liver lipid metabolism in silver foxes (Vulpes vulpes fulva) during the winter fur-growth period.

The proportion of n-6/n-3 polyunsaturated fatty acid (PUFA) plays an important role in regulating lipid metabolism. This study aimed to investigate the effects of dietary n-6/n-3 PUFA ratios on body fat deposition, tissues fatty acid composition, and gene expression of liver lipid metabolism of silver foxes during the winter fur growth period. Forty-eight age-matched male silver foxes with similar body weights were randomly divided into four dietary groups for 47 days, which were fed n-6/n-3 PUFA ratio with 3, 18, 41, and 136 experimental diets, respectively. Dietary n-6/n-3 PUFA ratio did not significantly influence fat deposition parameters except for hepatic fat content. The variation trend of the fatty acid composition of liver, intramuscular fat, and subcutaneous fat in silver fox was directly related to dietary fatty acid content (p < 0.05). With the dietary n-6/n-3 PUFA ratio increasing, the expression of liver fatty acid synthase (FAS) mRNA and peroxisome proliferator-activated receptor (PPAR) mRNA exhibited the trend of first decreasing and then increasing (p < 0.05), whereas L-fatty acid binding protein (L-FABP) mRNA expression showed a gradual increasing trend (p < 0.05). In summary, silver foxes fed an n-6/n-3 PUFA ratio 18:1 diet (supplementing with 9.38% corn oil and 4.62% soybean oil) was more conducive to lipid decomposition, PUFA transport, and utilization of tissues, thereby meeting it for supplying energy and withstanding the cold.

Iron overload accelerated lipid metabolism disorder and liver injury in rats with non-alcoholic fatty liver disease

Background/aimsNon-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. Iron overload has been implicated in chronic non-communicable liver diseases, but its relationship with NAFLD remains unclear. This study aimed to investigate the underlying roles of iron overload in the development of NAFLD.MethodsMale Sprague Dawley rats were fed with a high-fat diet (HFD) and/or iron for 8, 12, and 20 weeks. Some rats fed with HFD plus iron also received intraperitoneal injection of deferoxamine (DFO) for 8 weeks. Liver steatosis, lipid metabolism and injury were evaluated.ResultsA NAFLD model, including typical liver steatosis, was established by feeding rats with a HFD, while iron overload alone is not enough to induce severe NAFL. Compared with rats fed a HFD, excess iron further increased lipid accumulation, serum levels of lipids, enzymes of liver function, and expression levels of CD36 and FAS in rat liver. In addition, iron overload decreased the activities of antioxidative enzymes in liver compared with HFD rats. The levels of CPT1 and the ratios of p-ACC/ACC were also decreased by iron overload. DFO effectively reversed the abnormal lipid metabolism and liver damage induced by a high-fat, high-iron diet.ConclusionA HFD plus iron overload might synergistically aggravate lipid metabolism disorders, liver injury, and oxidative damage, compared with a HFD alone. DFO might help to alleviate lipid metabolism dysfunction and improve the pathogenesis of NAFLD.