Can Nutraceuticals Support the Treatment of MASLD/MASH, and thus Affect the Process of Liver Fibrosis?

Currently, metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are considered to be the main causes of fibrosis. In turn, fibrosis may lead to the development of hepatocellular carcinoma or advanced cirrhosis, i.e., potentially life-threatening conditions. It is likely that therapy aimed at reducing the risk of developing hepatic steatosis and inflammation could be helpful in minimizing the threat/probability of organ fibrosis. In recent years, increasing attention has been paid to the influence of nutraceuticals in the prevention and treatment of liver diseases. Therefore, the aim of this review was to describe the precise role of selected ingredients such as vitamin C, beta-carotene, omega-3 fatty acids, and curcumin. It is likely that the use of these ingredients in the treatment of patients with MASLD/MASH, along with behavioral and pharmacological therapy, may have a beneficial effect on combating inflammation, reducing oxidative stress, and thereby preventing liver damage.

Short-term reduction of dietary gluten improves metabolic-dysfunction associated steatotic liver disease: A randomised, controlled proof-of-concept study.

BACKGROUND: The current management of metabolic dysfunction-associated steatotic liver disease (MASLD) relies on lifestyle intervention. Prior studies have shown that nutritional wheat amylase trypsin inhibitors (ATI) activate toll-like receptor 4 on intestinal myeloid cells to enhance intestinal and extra-intestinal inflammation, including the promotion of murine MASLD, insulin resistance and liver fibrosis. AIMS: We aimed to assess the impact of ATI (gluten)-free diet in liver as well as metabolic parameters of biopsy-proven MASLD patients. METHODS: We performed a 6-week, proof-of-concept 1:1 randomised controlled trial of an ATI-free diet. The controls followed a balanced diet recommended by the German Nutrition Society. We assessed changes in controlled attenuation parameter (CAP), body mass index (BMI) and homeostatic model assessment of insulin resistance (HOMA-IR). Patient-reported outcomes were assessed by the CLDQ-NASH questionnaire. Forty-five patients were consecutively enrolled (21 in the intervention arm and 24 in the control arm). RESULTS: Three patients from each arm discontinued the study. In the ATI-free diet group, a significant decrease in BMI (p = 0.018), CAP (p = 0.018) and HOMA-IR (p = 0.042) was observed at 6 weeks. The mean difference in CAP between the two arms at week 6 was 30.5 dB/m (p = 0.039), with a delta significantly higher in the ATI-free diet group (p = 0.043). Only an ATI-free diet could achieve a significant improvement in CLDQ-NASH domains (p value for total scoring: 0.013). CONCLUSIONS: A short-term ATI-free diet leads to significant improvements in liver and metabolic parameters, as well as patient-reported outcomes with good tolerability. A larger follow-up study is justified to corroborate these findings. CLINICAL TRIAL NUMBER: NCT04066400.

What Is the Optimal Time on a Low-Calorie Diet Prior to Laparoscopic Anti-reflux Surgery? A Prospective Case-Controlled Study.

INTRODUCTION: A very low-calorie diet (VLCD) or low-calorie diet (LCD) is often used prior to laparoscopic surgery to optimize access to the hiatus. Much debate exists in the literature regarding the required duration for a VLCD or LCD, and how to evaluate the presence of a fatty liver. The aim of our study was to determine the optimal amount of time on an LCD to achieve maximal liver volume reduction, and to assess the accuracy of the InBody 230® vs. bedside ultrasonography vs. magnetic resonance imaging (MRI) in the measurement of liver volume. METHODS: Seventeen consecutive patients undergoing laparoscopic anti-reflux surgery were recruited into the study. Each patient underwent body composition analysis with the InBody® 230, liver ultrasound, and liver MRI. Patients then began an LCD with a weekly ultrasound assessment until the day before surgery when they underwent repeat body composition analysis, liver ultrasound, and MRI. RESULTS: The mean age was 54 years (range 21, 74). Maximal liver volume loss was noted within 3 weeks for 88% of participants, with 47% achieving their maximal liver volume reduction after the first week of an LCD. The mean reduction in liver volume was 16%, 18.6%, and 19% for MRI, ultrasound, and body composition analysis, respectively. CONCLUSION: Close to 90% of patients require 3 weeks or less on an LCD to achieve maximal liver volume loss prior to laparoscopic anti-reflux surgery. Body composition analysis and bedside ultrasonography were both as accurate as the gold standard MRI in the assessment of liver volume.

Multidimensional Impact of Mediterranean Diet on IBD Patients.

BACKGROUND & AIMS: Malnutrition with the accumulation of fat tissue and nonalcoholic fatty liver disease (NAFLD) are conditions associated with inflammatory bowel disease (IBD). Visceral fat and NAFLD-related liver dysfunction can both worsen intestinal inflammation. Because the Mediterranean diet (Md) has been shown to ameliorate both obesity and NAFLD, the aim of this study was to analyze the impact of Md on the nutritional state, liver steatosis, clinical disease activity, and quality of life (QoL) in IBD patients. METHODS: Patients with IBD, both Crohn's disease (CD) and ulcerative colitis (UC), followed Md for 6 months. Their body mass index (BMI), body tissue composition, liver steatosis and function, serum lipid profile, clinical disease activity, and inflammatory biomarkers (C-reactive protein and fecal calprotectin) were collected at baseline (T0) and compared with those obtained after 6 months (T180) to evaluate the impact of Md. RESULTS: One hundred forty-two IBD patients, 84 UC and 58 CD, followed Md for 6 months. At T180, diet-adherent CD and UC improved BMI (UC -0.42, P = 0.002; CD -0.48, P = 0.032) and waist circumference (UC -1.25 cm, P = 0.037; CD -1.37 cm, P = 0.041). Additionally, the number of patients affected by liver steatosis of any grade was significantly reduced in both groups (UC T0 31 of 84 [36.9%] vs T180 18 of 84 [21.4%], P = 0.0016; CD T0 27 of 58 [46.6%] vs T180 18 of 58 [31.0%], P < 0.001) after dietary intervention. Finally, after 6 months of the diet, fewer UC and CD patients with stable therapy had active disease (UC T0 14 of 59 [23.7%] vs T180 4 of 59 [6.8%], P = 0.004; CD T0 9 of 51 [17.6%] vs T180 2 of 51 [3.0%], P = 0.011) and elevated inflammatory biomarkers. Mediterranean diet improved QoL in both UC and CD, but neither serum lipid profile nor liver function were modified by the diet. CONCLUSIONS: A significant reduction of malnutrition-related parameters and liver steatosis was observed in both CD and UC patients after short-term dietary intervention based on the adoption of Md, and this was associated with a spontaneous improvement of disease activity and inflammatory markers.

Eficácia e segurança de mudanças no estilo de vida na Esteatose Hepática não Alcoólica: revisão rápida de evidências / Effectiveness and safety of lifestyle modifications for Nonalcoholic Hepatic Steatosis: rapid response review of evidence

Tecnologia: Intervenção de mudança no estilo de vida (dieta, exercícios). Indicação: doença hepática gordurosa não alcoólica (DHGNA). Pergunta clínica: Intervenções de mudança no estilo de vida, comparados a nenhum tratamento ou placebo, são eficazes no tratamento de DHGNA para modificar indicadores metabólicos, reduzir mortalidade e prevenir complicações relacionadas à esteatose hepática? Métodos: Foi feito levantamento bibliográfico na base de dados PUBMED, seguindo estratégias de buscas predefinidas. As revisões sistemáticas foram avaliadas com a ferramenta "AMSTAR 2 - Assessing the Methodological Quality of Systematic Reviews version 2". Resultados: Foram selecionadas 4 revisões sistemáticas, que atendiam aos critérios de inclusão. Conclusão: As evidências disponíveis não são suficientes para confirmar ou refutar que as modificações do estilo de vida têm efeitos benéficos de longo prazo sobre a DHGNA. Protocolos com dieta mediterrânea, jejum intermitente ou exercícios aeróbicos são benéficos para reduzir parâmetros metabólicos em pessoas com DHGNA

Technology: Lifestyle change intervention (diet, exercise). Indication: Non-alcoholic fatty liver disease (NAFLD). Clinical question: Are lifestyle change interventions, compared to no treatment or placebo, effective in NAFLD treatment to modify metabolic indicators, reduce mortality and prevent complications related to hepatic steatosis? Methods: A bibliographic survey was carried out in the PUBMED database, following predefined search strategies. Systematic reviews were evaluated using the tool "AMSTAR 2 - Assessing the Methodological Quality of Systematic Reviews version 2". Results: 4 systematic reviews that met the inclusion criteria were selected. Conclusion: The available evidence is not sufficient to confirm or refute that lifestyle modifications have long-term beneficial effects on NAFLD. Protocols such as a Mediterranean diet, intermittent fasting, or aerobic exercise are beneficial in reducing metabolic parameters in people with NAFLD

Study on the new strategy and key techniques for accurate prevention and treatment of nonalcoholic steatohepatitis based on intestinal target bacteria.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has emerged as a major health problem worldwide; according to statistics, 10% to 25% of patients with NAFLD can progress to nonalcoholic steatohepatitis (NASH). A link between the composition and metabolites of intestinal microbiota and the development of NAFLD is becoming clearer. It is believed that microbiota factors are driving forces of hepatic steatosis and inflammation. The formulated food that contains prebiotics and dietary fiber may improve NAFLD by altering the intestinal flora and its metabolites. METHODS: The study plan to recruit adult patients (18-75 years, n = 120) with NAFLD, range of alanine aminotransferase is 1.5 to 5 times upper limit of normal (ULN) or liver biopsy is confirmed as NASH. Participants will be randomly allocated into 2 groups: formulated food (n = 80) and a placebo group (n = 40) for 24 weeks. Both groups will receive lifestyle and nutritional advice. The primary endpoint is a decrease in MRS-PDFF by more than 30% from baseline at 24 weeks. The secondary endpoints include the change of anthropometric, liver function, glycolipid metabolism, and systemic inflammation at 4, 12, and 24 weeks. In addition, we consider the changes in intestinal microbiota as an exploration to assess the abundance and diversity at 24 weeks. Weeks 24 to 36 are the follow-up period of drug withdrawal. DISCUSSION: This clinical trial will provide evidence of efficacy and safety of formulated food as a potential new therapeutic agent for NAFLD patients. TRIAL REGISTRATION: The trial is registered in the China Clinical Trial Center (ChiCTR1800016178).

Thrombospondin 1 improves hepatic steatosis in diet-induced insulin-resistant mice and is associated with hepatic fat content in humans.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with altered production of secreted proteins. Increased understanding of secreted proteins could lead to improved prediction and treatment of NAFLD. Here, we aimed to discover novel secreted proteins in humans that are associated with hepatic fat content using unbiased proteomic profiling strategy, and how the identified Thbs1 modulates lipid metabolism and hepatic steatosis. METHOD: NAFLD patients were enrolled and treated with lifestyle intervention. Patients who underwent liver biopsy were enrolled for analyzing the correlation between circulating Thbs1 and liver steatosis. Mice were fed on high-fat, high-sucrose diet and treated with recombinant Thbs1. Primary hepatocytes isolated from CD36 knockout (CD36-/-) mice and their wild-type littermates (controls) were treated with glucose plus insulin for 24 h together with or without recombinant Thbs1. FINDING: Serum Thbs1 levels are increased in participants with NAFLD and positively associated with liver steatosis grades. Improvement of liver steatosis after lifestyle intervention was accompanied with significant reduction of serum Thbs1 levels. Pharmacological administration of recombinant human Thbs1 attenuates hepatic steatosis in diet-induced obese mice. Treatment with Thbs1 protein or stably overexpression of Thbs1 causes a significant reduction of lipid accumulation in primary hepatocytes or HepG2 cells exposed to high glucose plus insulin, suggesting that Thbs1 regulates lipid metabolism in a hepatocyte-autonomous manner. Mechanistically, Thbs1 inhibits cleavage and processing of SREBP-1, leading to a reduction of target lipogenic gene expression and hepatic steatosis. Inhibitory effects of Thbs1 on lipogenesis and triglyceride accumulation are abrogated in CD36 deficient primary hepatocytes exposed to high glucose plus insulin. Interestingly, beneficial effects of Thbs1 on lipid accumulation are observed in primary hepatocytes treated with a Thbs1 nonapeptide mimetic ABT-526. INTERPRETATION: Thbs1 is a biomarker for NAFLD in humans, and pharmacological and genetic approaches for the modulation of Thbs1 activity may have the therapeutic potential for treating hepatic steatosis. FUND: A full list of funding bodies that contributed to this study can be found in the Funding Sources section.

Lacto-Fermented Cauliflower Fungus (Sparassis crispa) Ameliorates Hepatic Steatosis by Activating Beta-Oxidation in Diet-Induced Obese Zebrafish.

Sparassis crispa (SC), known as cauliflower mushroom, possesses a wide variety of health-promoting properties and a high content of ß-glucans. Its nutritional properties are enhanced by fermentation. In this study, we examined the efficacy of Lactobacillus-fermented (lacto-fermented) SC against obesity using a zebrafish model. We first fermented SC by Lactobacillus paracasei, denoted as lacto-fermented SC (L-SC), for 48 h and then orally administered SC or L-SC to diet-induced obese zebrafish for 4 weeks. Results demonstrated that the L-SC group (20 µg/gBW/day) significantly (P < .01) suppressed body weight gain and ameliorated lipid accumulation in liver tissues, whereas SC did not exhibit antiobesity effects. We further performed expression analysis of genes related to lipid metabolism in the liver and visceral adipose tissues (VAT) in L-SC-administered fish. In liver tissues, L-SC upregulated (P < .05) expression of genes involved in peroxisome proliferator-activated receptor alpha pathways, suggesting that the lipid-lowering property of L-SC is caused by activation of beta-oxidation. In VAT, L-SC did not show significant changes between the experimental groups. No difference was observed between the ß-glucan contents of SC (43.8 g/100 g) and L-SC (44.3 g/100 g); however, ß-glucan levels in the hot-water extracts increased 20-fold in L-SC (37.2 g/100 g) compared with those in SC (1.8 g/100 g). In summary, lacto-fermentation of SC enhances its lipid-lowering property and can prevent hepatic steatosis through activation of beta-oxidation. Dietary supplementation of fermented L-SC as a functional food may be suitable for obesity prevention and reduction in the prevalence of obesity-related diseases.

Hepatic steatosis integrated approach: nutritional guidelines and joined nutraceutical administration.

BACKGROUND: The nonalcoholic fat liver disease (NAFLD) progresses in 30% of the patients to not alcoholic steatohepatitis (NASH) and subsequently in liver fibrosis and even primary cancer and death. Due to the complex physiopathology of the liver steatosis, NASH is an area orphan of specific drugs, but many authors suggest an integrated treatment based upon diet, lifestyle change, and pharmacology. METHODS: Our clinical study selected from a wider patient cohort, 13 subjects, appealing to the Second Opinion Medical Consulting Network, for liver and nutritional problems. The diet was integrated with regular prescription of an herbal derivative based on Chrysanthellum americanum and Pistacia lentiscus L. extracts. Clinical data of the recruited patients including body weight, Body Mass Index, were recorded before and after treatment. Each patient underwent pre-post accurate clinical examination and lab exams. The liver stiffness and liver steatosis were evaluated by a trained hepatologist with FibroScan®. RESULTS: A significant reduction of anthropometric parameters was detected in all the patients at the end of the study; liver fibrosis and steatosis were instrumentally decreased in 8 subjects, but not significant changes in lab exams and no adverse effects were reported. CONCLUSIONS: Chrysanthellum americanum and Pistacia lentiscus L. extracts were absolutely safe and effective and gave a substantial contribution to the life quality benefit, metabolic balance and gut function in patients with hepatic steatosis.

Heterogeneity in liver histopathology is associated with GSK-3ß activity and mitochondrial dysfunction in end-stage diabetic rats on differential diets.

While liver histopathology is heterogeneous in diabetes, the underlying mechanisms remain unclear. We investigated whether glycemic variation resulting from differential diets can induce heterogeneity in diabetic liver and the underlying molecular mechanisms. We generated end-stage non-obese diabetic model rats by subtotal-pancreatectomy in male Sprague- Dawley rats and ad libitum diet for 7 weeks (n = 33). The rats were then divided into three groups, and fed a standard- or a low-protein diet (18 or 6 kcal%, respectively), for another 7 weeks: to maintain hyperglycemia, 11 rats were fed ad libitum (18AL group); to achieve euglycemia, 11 were calorierestricted (18R group), and 11 were both calorie- and proteinrestricted with the low-protein diet (6R group). Overnightfasted liver samples were collected after the differential diets together with sham-control (18S group), and histology and molecular changes were compared. Hyperglycemic-18AL showed glycogenic hepatopathy (GH) without steatosis, with the highest GSK-3ß inactivation because of Akt activation during hyperglycemia; mitochondrial function was not impaired, compared to the 18S group. Euglycemic-18R showed neither GH nor steatosis, with intermediate GSK-3ß activation and mitochondrial dysfunction. However, euglycemic-6R showed both GH and steatosis despite the highest GSK-3ß activity and no molecular evidence of increased lipogenesis or decreased ApoB expression, where mitochondrial dysfunction was highest among the groups. In conclusion, heterogeneous liver histopathology developed in end-stage non-obese diabetic rats as the glycemic levels varied with differential diets, in which protein content in the diets as well as glycemic levels differentially influenced GSK-3ß activity and mitochondrial function in insulin-deficient state. [BMB Reports 2020; 53(2): 100-105].

[Nutritional Management of Nonalcoholic fatty liver disease (NAFLD)]. / Interventions nutritionnelles dans la prise en charge de la stéatose et la stéatohépatite non alcoolique.

Nonalcoholic fatty liver disease (NAFLD) is strongly associated with obesity and insulin resistance. There is currently no pharmacological treatment validated in steatosis. The combination of weight loss and adequate physical activity can improve liver steatosis. In randomized trials and cohort studies, a weight loss of at least 7% and a diet approaching the Mediterranean diet have been associated with an improvement in hepatic fat content, an improvement in hepatic biomarkers, and regression of histological signs of steatosis. Bariatric surgery by losing weight can lead to an improvement in hepatic fat content.

Cold-pressed Canola Oil Reduces Hepatic Steatosis by Modulating Oxidative Stress and Lipid Metabolism in KM Mice Compared with Refined Bleached Deodorized Canola Oil.

The quality of canola oil is affected by different extraction methods. The effect of cold-pressed canola oil (CPCO) diet and traditional refined bleached deodorized canola oil (RBDCO) diet on lipid accumulation and hepatic steatosis in mice were investigated. The body weight, peroxisome proliferator-activated receptor-α concentration, serum lipid profile, insulin sensitivity, and oxidative stress were increased in mice fed with CPCO diet, which had higher unsaturated fatty acid, tocopherols, phytosterols, and phospholipids but lower saturated fatty acid than RBDCO, after 12 weeks,. Moreover, CPCO significantly increased tocopherols and phytosterols content in liver and reduced liver cholesterol contents and lipid vacuoles accumulation than RBDCO. Also, serum proinflammatory cytokines, 3-hydroxy-3-methylglutary coenzyme A reductase expression level, lipogenic enzymes, and transcriptional factors such as sterol regulatory element-binding proteins 1c, acetyl-CoA carboxylase, and fatty acid synthase in the liver were also markedly downregulated from CPCO diet mice. Overall, CPCO can reduce lipid accumulation and hepatic steatosis by regulating oxidative stress and lipid metabolism in Kun Ming mice compared with RBDCO. PRACTICAL APPLICATION: The results suggested that more bioactive components were contained in cold-pressed canola oil (CPCO) rather than refined bleached deodorized canola oil (RBDCO). CPCO could lower the risk of obesity and hyperlipidemia, reduce lipid accumulation, and prevent hepatic steatosis. It could be considered as a kind of better edible oil than RBDCO.

Four Weeks of Preoperative Omega-3 Fatty Acids Reduce Liver Volume: a Randomised Controlled Trial.

PURPOSE: Weight loss before bariatric surgery with a low-calorie diet (LCD) has several advantages, including reduction of liver volume and an improved access to the lesser sac. Disadvantages include performing surgery in a state of undernutrition, side effects, costs and patient compliance. Omega-3 fatty acids may serve as an alternative to reduce liver steatosis. MATERIALS AND METHODS: A randomised controlled open-label trial was done to compare the effects of a LCD with Modifast (800 kcal/day) during 2 weeks with 2 g of omega-3 fatty acids a day and a normal diet (2000 kcal/day) during 4 weeks. Total liver volume (TLV) and volume of the left liver lobe (LLL), visceral fat area (VFA) and muscle area (SMA) at the L3-L4 level were measured with MRI before and after preoperative treatment. RESULTS: Sixty-two morbidly obese women undergoing laparoscopic Roux-en-Y gastric bypass surgery (LRYGB) were recruited. In both groups, there was a significant decrease in LLL, TLV and VFA. For LLL and TLV reduction, the LCD had a significantly larger effect (p < 0.05). Only in the LCD group was there a significant decrease in SMA with significantly more side effects and worse compliance. CONCLUSION: Both the LCD and omega-3 diet reduced LLL, TLV and VFA. The LCD outperformed the omega-3 diet in LLL and TLV reduction, but induced significant loss of SMA and had worse compliance due to more side effects. Omega-3 fatty acids may provide a safe and more patient-friendly alternative for a LCD and further research is indicated. TRIAL REGISTRATION: The study is registered at www.clinicaltrials.gov (NCT02206256).

Effective Food Ingredients for Fatty Liver: Soy Protein ß-Conglycinin and Fish Oil.

Obesity is prevalent in modern society because of a lifestyle consisting of high dietary fat and sucrose consumption combined with little exercise. Among the consequences of obesity are the emerging epidemics of hepatic steatosis and nonalcoholic fatty liver disease (NAFLD). Sterol regulatory element-binding protein-1c (SREBP-1c) is a transcription factor that stimulates gene expression related to de novo lipogenesis in the liver. In response to a high-fat diet, the expression of peroxisome proliferator-activated receptor (PPAR) γ2, another nuclear receptor, is increased, which leads to the development of NAFLD. ß-Conglycinin, a soy protein, prevents NAFLD induced by diets high in sucrose/fructose or fat by decreasing the expression and function of these nuclear receptors. ß-Conglycinin also improves NAFLD via the same mechanism as for prevention. Fish oil contains n-3 polyunsaturated fatty acids such as eicosapentaenoic acid and docosahexaenoic acid. Fish oil is more effective at preventing NAFLD induced by sucrose/fructose because SREBP-1c activity is inhibited. However, the effect of fish oil on NAFLD induced by fat is controversial because fish oil further increases PPARγ2 expression, depending upon the experimental conditions. Alcohol intake also causes an alcoholic fatty liver, which is induced by increased SREBP-1c and PPARγ2 expression and decreased PPARα expression. ß-Conglycinin and fish oil are effective at preventing alcoholic fatty liver because ß-conglycinin decreases the function of SREBP-1c and PPARγ2, and fish oil decreases the function of SREBP-1c and increases that of PPARα.

Hexane-Isopropanolic Extract of Tungrymbai, a North-East Indian fermented soybean food prevents hepatic steatosis via regulating AMPK-mediated SREBP/FAS/ACC/HMGCR and PPARα/CPT1A/UCP2 pathways.

This study for the first time examined the prophylactic role of Tungrymbai, a well-known fermented soybean food of North-East India, against hepatic steatosis. Treatment with hexane-isopropanolic (2:1, HIET) but not hydro-alcoholic (70% ethanol, HAET) extract dose-dependently (0.1, 0.2, or 0.3 µg/mL) reduced the intracellular lipid accumulation as shown by lower triglyceride levels and both Oil Red O and Nile Red staining in palmitate (PA, 0.75 mM)-treated hepatocytes. Immunobloting, mRNA expression, and knock-down studies demonstrated the role of AMPK-mediated SREBP/FAS/ACC/HMGCR and PPARα/CPT1A/UCP2 signaling pathways in facilitating the beneficial role of HIET against lipid accumulation in PA-treated hepatocytes. Animal studies further showed a positive effect of HIET (20 µg/kg BW, 8 weeks, daily) in regulating AMPK/SREBP/PPARα signaling pathways and reducing body weight gain, plasma lipid levels, and hepatic steatosis in high fat diet (HFD)-fed mice. Histological analyses also revealed the beneficial effect of HIET in reducing hepatic fat accumulation in HFD mice. Chemical profiling (HRMS, IR, and HPLC) demonstrated the presence of menaquinone-7 (vitamin K2) as one of the bio-active principle(s) in HIET. Combining all, this study demonstrates the positive effect of HIET on reducing hepatic steatosis via regulating AMPK/SREBP/PPARα signaling pathway.

The Effects of Extra Virgin Olive Oil on Alanine Aminotransferase, Aspartate Aminotransferase, and Ultrasonographic Indices of Hepatic Steatosis in Nonalcoholic Fatty Liver Disease Patients Undergoing Low Calorie Diet.

Background: Coronary artery disease is the most common cause of death in the patients with nonalcoholic fatty liver disease (NAFLD). Studies have shown that there is a strong relation between the increase in the aminotransferase levels and fat accumulation in the liver with cardiovascular complications, independent of all aspects of the metabolic syndrome. This study aimed to examine the effect of virgin olive oil on alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the severity of steatosis in the NAFLD patients undergoing a weight-loss diet. Methods: This clinical trial was carried out on 50 patients with nonalcoholic fatty liver (mean age of 45.91 ± 9.61 years, mean BMI of 29.7 ± 0.58 Kg/m2) and the subjects were randomly assigned to the olive oil group (receiving the equivalent of 20% of their total daily energy requirement from olive oil) or the control group (with normal consumption of oil) for 12 weeks. All the patients received a hypocaloric diet during the study. At the beginning and the end of the study, the serum levels of ALT and AST and liver steatosis were measured. Findings: A significant decrease in the level of ALT enzymes was observed in the control group at the end of the study (P = 0.004). In the olive oil group, both enzymes decreased compared to baseline measurements (P < 0.01). There were significant differences in the ALT and AST levels between the two groups (P < 0.02). The severity of liver steatosis did not change significantly during the study. Conclusion: The consumption of a low calorie diet enriched with olive oil, along with slight weight reduction, reinforces the desired effects of weight loss in improving the levels of the hepatic enzymes.

Lychee (Litchi chinensis Sonn) peel flour: effects on hepatoprotection and dyslipidemia induced by a hypercholesterolemic diet

ABSTRACT Dyslipidemias are associated with the incidence of cardiovascular diseases, obesity, diabetes, hypertension and hepatic steatosis, being the cause of morbidity and mortality. This study investigated the effects of lychee peel flour (PF) on serum levels of total cholesterol (TC), low-density lipoprotein (LDL-c), triacylglycerols (TAG) and various parameters related to obesity, in rats fed a hypercholesterolemic diet. Therefore, 20 male rats were used. In the first 21 days, the animals were fed a hypercholesterolemic diet, except for control group. In the following 21 days, their diets were modified, and they received a standard diet (Control); hypercholesterolemic (Hyper); hypercholesterolemic + 5% PF (PF5) and hypercholesterolemic + 10% PF (PF10). The results revealed that PF intake attenuated weight gain, reduced body mass index, glucose and the levels of TAG, TC, LDL-c, hepatic enzymes and leptin, besides the percentage of hepatic lipids, liver lipid peroxidation and frequency of severe steatosis. Histological studies of the aorta did not show the formation of the atheromatous plaque. These results reinforce its potential to reduce the risk of diseases associated with obesity.

In vitro assessment of nutraceutical compounds and novel nutraceutical formulations in a liver-steatosis-based model.

BACKGROUND: Steatosis is a chronic liver disease that depends on the accumulation of intracellular fatty acids. Currently, no drug treatment has been licensed for steatosis; thus, only nutritional guidelines are indicated to reduce its progression. The aim of this study is to combine different nutraceutical compounds in order to evaluate their synergistic effects on a steatosis in vitro model compared to their separate use. In particular, three different formulations based on silymarin, curcumin, vitamin E, docosahexaenoic acid (DHA), choline, and phosphatidylcholine were assayed. METHODS: Human hepatocellular carcinoma cells (HepG2 cell line) were treated with a mixture of fatty acids in order to induce an in vitro model of steatosic cells, and then the amount of intracellular fat was evaluated by Oil Red O staining. The peroxisome proliferator-activated receptors α and γ (PPARα and γ) expression, closely correlated to lipid metabolism, was evaluated. The efficiency of these receptors was evaluated through the study of LPL mRNA expression, a marker involved in the lipolysis mechanism. Superoxide dismutase (SOD-2) and malondialdehydes (MDA) in lipid peroxidation were assayed as specific biomarkers of oxidative stress. In addition, experiments were performed using human liver cells stressed to obtain a steatosis model. In particular, the content of the intracellular fat was assayed using Oil Red O staining, the activation of PPARα and γ was evaluated through western blotting analyses, and the LPL mRNA expression level was analyzed through qRT-PCR. RESULTS: All formulations proved effective on lipid content reduction of about 35%. The oxidative stress damage was reduced by all the substances separately and even more efficiently by the same in formulation (i.e. Formulation 1 and Formulation 3, which reduced the SOD-2 expression and induced the PPARs activation). Lipid peroxidation, was reduced about 2 fold by foormulation2 and up to 5 fold by the others compared to the cells pretreated with H2O2.Formulation 1, was more effective on PPARγ expression (2.5 fold increase) respect to the other compounds on FA treated hepathocytes. Beside, LPL was activated also by Formulation 3 and resulted in a 5 to 9 fold-increase respect to FA treated control. CONCLUSIONS: Our results proved that the formulations tested could be considered suitable support to face steatosis disease beside the mandatory dietetic regimen.

Antioxidant dietary approach in treatment of fatty liver: New insights and updates.

Non-alcoholic fatty liver disease (NAFLD) is a common clinicopathological condition, encompassing a range of conditions caused by lipid deposition within liver cells. To date, no approved drugs are available for the treatment of NAFLD, despite the fact that it represents a serious and growing clinical problem in the Western world. Identification of the molecular mechanisms leading to NAFLD-related fat accumulation, mitochondrial dysfunction and oxidative balance impairment facilitates the development of specific interventions aimed at preventing the progression of hepatic steatosis. In this review, we focus our attention on the role of dysfunctions in mitochondrial bioenergetics in the pathogenesis of fatty liver. Major data from the literature about the mitochondrial targeting of some antioxidant molecules as a potential treatment for hepatic steatosis are described and critically analysed. There is ample evidence of the positive effects of several classes of antioxidants, such as polyphenols (i.e., resveratrol, quercetin, coumestrol, anthocyanins, epigallocatechin gallate and curcumin), carotenoids (i.e., lycopene, astaxanthin and fucoxanthin) and glucosinolates (i.e., glucoraphanin, sulforaphane, sinigrin and allyl-isothiocyanate), on the reversion of fatty liver. Although the mechanism of action is not yet fully elucidated, in some cases an indirect interaction with mitochondrial metabolism is expected. We believe that such knowledge will eventually translate into the development of novel therapeutic approaches for fatty liver.