Association between Non-Alcoholic Fatty Liver Disease and Mediterranean Lifestyle: A Systematic Review

Background and Aims: Non-alcoholic fatty liver disease (NAFLD) is an excessive accumulation of fat in the liver without alcohol abuse. It is linked to metabolic syndrome (MetS) and no pharmacological treatment exists. This systematic review aims to assess evidence about the effect of Mediterranean lifestyle on the prevention and reversion of NAFLD. Methods: A systematic literature search was performed in MEDLINE via Pubmed. MeSH terms used were: non-alcoholic fatty liver disease [MeSH Major Topic] AND metabolic syndrome [MeSH Term] AND (Diet, Mediterranean [MeSH Term]) OR (Exercise [MeSH Term]). (PROSPERO ID: 2021 CRD42021289495). Results: Thirteen articles were selected and divided into two categories (four focused on Mediterranean diet and NAFLD and nine focused on Mediterranean diet, physical activity, and NAFLD). Information of clinical endpoints was based on NAFLD, as well as MetS, body mass index, fasting glycemia, obesity, cholesterol, triglycerides, transaminases, albuminuria, and hepatic steatosis, among others. All studies found beneficial associations between the clinical parameters of NAFLD/MetS and following a Mediterranean diet and regular physical activity. Conclusions: An effective treatment that prevents, and even reverses, NAFLD is to adapt lifestyle to the Mediterranean one, based on a Mediterranean diet and regular physical activity.     

Sodium Alginate Prevents Non-Alcoholic Fatty Liver Disease by Modulating the Gut–Liver Axis in High-Fat Diet-Fed Rats

Previous studies have suggested that the sodium alginate (SA) is beneficial for the treatment of non-alcoholic fatty liver disease (NAFLD), while the potential mechanisms are largely unknown. The present study aimed to clarify the effects and potential mechanisms of SA in preventing NAFLD via the gut−liver axis. Thirty-two male Sprague−Dawley rats were randomly divided into four groups: normal control group (NC); high-fat diet group (HFD); HFD with 50 mg/kg/d sodium alginate group (LSA); HFD with 150 mg/kg/d sodium alginate group (HSA). After 16 weeks, the rats were scarified to collect blood and tissues. The results indicated that SA significantly reduced their body weight, hepatic steatosis, serum triglyceride (TG), alanine transaminase (ALT) and tumor necrosis factor α (TNF-α) levels and increased serum high-density lipoprotein-cholesterol (HDL-C) levels in comparison with HFD group (p < 0.05). The elevated mRNA and protein expression of genes related to the toll-like receptor 4 (TLR-4)/nuclear factor-kappa B (NF-κB)/nod-like receptor protein 3 (NLRP3) inflammatory signaling pathway in the liver of HFD-fed rats was notably suppressed by SA. In terms of the gut microbiota, the LSA group showed a significantly higher fecal abundance of Oscillospiraceae_UCG_005, Butyricicoccaceae_UCG_009 and Colidextribacter compared with the HFD group (p < 0.05). The rats in the HSA group had a higher abundance of unclassified_Lachnospiraceae, Colidextribacter and Oscillibacter compared with the HFD-associated gut community (p < 0.05). In addition, rats treated with SA showed a significant increase in fecal short chain fatty acids (SCFAs) levels and a decline in serum lipopolysaccharide (LPS) levels compared with the HFD group (p < 0.05). Moreover, the modulated bacteria and microbial metabolites were notably correlated with the amelioration of NAFLD-related indices and activation of the hepatic TLR4/NF-κB/NLRP3 pathway. In conclusion, SA prevented NAFLD and the potential mechanism was related to the modulation of the gut–liver axis.     

High Compliance to Mediterranean Diet Associates with Lower Platelet Activation and Liver Collagen Deposition in Patients with Nonalcoholic Fatty Liver Disease

The Mediterranean diet (Med-Diet) is considered the most effective dietary patterns to obtain weight loss in NAFLD patients. Previous evidence suggested that Med-Diet adherence could reduce cardiovascular risk and have a beneficial effect on NAFLD severity. Aim of the study was to investigate the relationship between Med-Diet adherence, platelet activation (PA), and liver collagen deposition. The study was performed in 655 consecutive NAFLD outpatients from the PLINIO study, a prospective observational cohort study aimed to identify non-conventional predictors of liver fibrosis progression in NAFLD. PA was measured by the serum thromboxane B₂ (TxB₂), and liver collagen deposition by N-terminal propeptide of type III collagen (Pro-C3). Adherence to the Med-diet was investigated by a short nine-item validated dietary questionnaire. Patients with high Med-Diet adherence were older and had less metabolic syndrome and lower serum triglycerides, GGT, TxB₂, and Pro-C3. At multivariate regression analyses, in the linear model, the Med-Diet score negatively correlated with both TxB₂ (Beta = −0.106; p = 0.009) and Pro-C3 (Beta = −0.121; p = 0.002) and in the logistic model high adherence inversely correlated with higher TxB₂ tertiles (II tertile: OR = 0.576, p = 0.044; III tertile: OR = 0.556, p = 0.026) and Pro-C3 tertile (III tertile: OR = 0.488, p = 0.013). Low consumption of red meat inversely correlated with higher TxB₂ tertile (II tertile: OR = 0.448, p < 0.001, III tertile: OR = 0.567, p = 0.004). In conclusion, NAFLD patients with high adherence to the Med-Diet show lower PA and liver collagen deposition, suggesting a protective role of the Med-Diet against NAFLD progression and cardiovascular risk. In addition, the correlation between TxB₂ and Pro-C3 suggests a link between NAFLD severity and cardiovascular risk.     

Association between Physical Activity and Non-Alcoholic Fatty Liver Disease in Adults with Metabolic Syndrome: The FLIPAN Study

Background: A lifestyle with regular PA (physical activity) and Mediterranean diet has benefits on NAFLD (non-alcoholic fatty liver disease) and MetS (metabolic syndrome). Objectives: To assess the association between physical activity and NAFLD in adults with MetS. Design: Cross-sectional study in 155 participants (40–60 years old) from Balearic Islands and Navarra (Spain) with diagnosis of NAFLD and MetS, and BMI (body mass index) between 27 and 40 Kg/m². Methods: PA level was categorized into two groups according to weekly METs (metabolic equivalents of tasks). PA was assessed using a validated Minnesota questionnaire and accelerometers. MetS parameters were assessed by blood collection analysis and NAFLD by abdominal MRI (magnetic resonance imaging). Results: Participants with high PA showed more energy expenditure and expended more calories than ingested (−143.9 Kcal/day; p < 0.001). PA was a risk factor for AST (aspartate aminotransferase) (adjusted OR: 7.26; 95% CI: 1.79–29.40) and a protective factor for ALT (alanine aminotransferase) (adjusted OR: 0.24; 95% CI: 0.12–0.48), GGT (gamma-glutamyl transferase) (adjusted OR: 0.52; 95% CI: 0.29–0.94) and IFC-NMR (intrahepatic fat content by nuclear magnetic resonance) (adjusted OR: 0.26; 95% CI: 0.12–0.56) when sociodemographic confounders were considered. Conclusions: NAFLD patients with high PA showed more positive relationship on MetS parameters and liver profile (ALT, GGT, IFC-NMR) than subjects with low PA, but not for AST. Difference between calories ingested and expended influenced this relationship.     

Dietary Patterns Modulate the Risk of Non-Alcoholic Fatty Liver Disease in Chinese Adults

Although previous studies reported the associations between the intakes of individual foods or nutrients and the risk of non-alcoholic fatty liver disease (NAFLD), the relationship between dietary patterns and NAFLD in the Chinese population has been rarely studied to date. This study aimed to investigate the associations between dietary patterns and the risk of NAFLD in a middle-aged Chinese population. The Study subjects were 999 Chinese adults aged 45–60 years in the Anhui province who participated in the Hefei Nutrition and Health Study. Dietary intake was collected by a semi-quantitative food frequency questionnaire. NAFLD was defined as the presence of moderate-severe hepatic steatosis (by B-ultrasonic examination); the absence of excessive alcohol use (>20 g day⁻¹ in men and 10 g day⁻¹ in women); no use of steatogenic medications within the past six months; no exposure to hepatotoxins; and no history of bariatric surgery. Log-binomial regression analysis was used to examine the association between dietary patterns and NAFLD with adjustment of potential confounding variables. Out of 999 participants, 345 (34.5%) were classified as having NAFLD. Four major dietary patterns were identified: “Traditional Chinese”, “Animal food”, “Grains-vegetables” and “High-salt” dietary patterns. After adjusting for potential confounders, subjects in the highest quartile of the “Animal food” pattern scores had greater prevalence ratio for NAFLD (prevalence ratio (PR) = 1.354; 95% confidence interval (CI): 1.063–1.724; p < 0.05) than did those in the lowest quartile. After adjustment for body mass index (BMI), compared with the lowest quartile of the “Grains-vegetables” pattern, the highest quartile had a lower prevalence ratio for NAFLD (PR = 0.777; 95% CI: 0.618–0.977, p < 0.05). However, the “traditional Chinese” and “high-salt” dietary patterns showed no association with the risk of NAFLD. Our findings indicated that the “Animal food” dietary pattern was associated with an increased risk of NAFLD.     

Diet and Risk of Non-Alcoholic Fatty Liver Disease,Cirrhosis, and Liver Cancer: A Large Prospective Cohort Study in UK Biobank

Background and Aims: Epidemiological evidence has shown the association between nutritional habits and liver disease. However, results remain conflicting. This study investigated the influence of dietary factors on the risk of incident non-alcoholic fatty liver disease (NAFLD), cirrhosis, and liver cancer. Methods: Data from the UK Biobank database were analyzed (n = 372,492). According to baseline data from the food frequency questionnaire, two main dietary patterns (Western and prudent) were identified using principal component analysis. We used cox proportional hazards models to explore the associations of individual food groups and dietary patterns with NAFLD, cirrhosis, and liver cancer. Results: During a median follow-up of 12 years, 3527 hospitalized NAFLD, 1643 cirrhosis, and 669 liver cancer cases were recorded among 372,492 participants without prior history of cancer or chronic liver diseases at baseline. In multivariable adjusted analysis, participants in the high tertile of Western dietary pattern score had an 18% (95%CI = 1.09–1.29), 21% (95%CI = 1.07–1.37), and 24% (95%CI = 1.02–1.50) higher risk of incident NAFLD, liver cirrhosis, and liver cancer, respectively, compared with the low tertile. Participants in the high tertile of prudent scores had a 15% (95%CI = 0.75–0.96) lower risk of cirrhosis, as compared with those in the low tertile. In addition, the higher consumption of red meat and the lower consumption of fruit, cereal, tea, and dietary fiber were significantly associated with a higher risk of NAFLD, cirrhosis, and liver cancer (p_trend < 0.05). Conclusions: This large prospective cohort study showed that an increased intake of food from the Western dietary pattern could be correlated with an increased risk of chronic liver diseases, while the prudent pattern was only correlated with a reduced liver cirrhosis risk. These data may provide new insights into lifestyle interventions for the prevention of chronical liver diseases.     

Non-Alcoholic Fatty Liver Disease (NAFLD) and Its Connection with Insulin Resistance,Dyslipidemia, Atherosclerosis and Coronary Heart Disease

Non-alcoholic fatty liver disease is marked by hepatic fat accumulation not due to alcohol abuse. Several studies have demonstrated that NAFLD is associated with insulin resistance leading to a resistance in the antilipolytic effect of insulin in the adipose tissue with an increase of free fatty acids (FFAs). The increase of FFAs induces mitochondrial dysfunction and development of lipotoxicity. Moreover, in subjects with NAFLD, ectopic fat also accumulates as cardiac and pancreatic fat. In this review we analyzed the mechanisms that relate NAFLD with metabolic syndrome and dyslipidemia and its association with the development and progression of cardiovascular disease.     

Maternal One-Carbon Supplement Reduced the Risk of Non-Alcoholic Fatty Liver Disease in Male Offspring

Recent studies have suggested that prevention of obesity and non-alcoholic fatty liver disease (NAFLD) should start with maternal dietary management. We previously reported disrupted methionine cycle, associated with NAFLD, in male offspring liver due to maternal high-fat (HF) diet, thus we hypothesize that maternal one-carbon supplement may reduce the risk of NAFLD in offspring via the normalizing methionine cycle. To test it, female mice (F0) were exposed to either a maternal normal-fat diet (NF group) a maternal HF diet (HF group), or a maternal methyl donor supplement (H1S or H2S group) during gestation and lactation. The offspring male mice (F1) were exposed to a postweaning HF diet to promote NAFLD. While the HF offspring displayed obesity, glucose intolerance and hepatic steatosis, the H1S and H2S offspring avoided hepatic steatosis. This phenotype was associated with the normalization of the methionine cycle and the restoration of L-carnitine and AMPK activity. Furthermore, maternal HF diet induced epigenetic regulation of important genes involved in fatty acid oxidation and oxidative phosphorylation via DNA methylation modifications, which were recovered by maternal one-carbon supplementation. Our study provides evidence that maternal one-carbon supplement can reverse/block the adverse effects of maternal HF diet on promoting offspring NAFLD, suggesting a potential nutritional strategy that is administered to mothers to prevent NAFLD in the offspring.     

Overview of Non-Alcoholic Fatty Liver Disease (NAFLD) and the Role of Sugary Food Consumption and Other Dietary Components in Its Development

NAFLD is the world’s most common chronic liver disease, and its increasing prevalence parallels the global rise in diabetes and obesity. It is characterised by fat accumulation in the liver evolving to non-alcoholic steatohepatitis (NASH), an inflammatory subtype that can lead to liver fibrosis and cirrhosis. Currently, there is no effective pharmacotherapeutic treatment for NAFLD. Treatment is therefore based on lifestyle modifications including changes to diet and exercise, although it is unclear what the most effective form of intervention is. The aim of this review, then, is to discuss the role of specific nutrients and the effects of different dietary interventions on NAFLD. It is well established that an unhealthy diet rich in calories, sugars, and saturated fats and low in polyunsaturated fatty acids, fibre, and micronutrients plays a critical role in the development and progression of this disease. However, few clinical trials have evaluated the effects of nutrition interventions on NAFLD. We, therefore, summarise what is currently known about the effects of macronutrients, foods, and dietary patterns on NAFLD prevention and treatment. Most current guidelines recommend low-calorie, plant-based diets, such as the Mediterranean diet, as the most effective dietary pattern to treat NAFLD. More clinical trials are required, however, to identify the best evidence-based dietary treatment approach.     

Egg Consumption,Cardiovascular Disease and Cardiometabolic Risk Factors: The Interaction with Saturated Fatty Acids. Results from the ATTICA Cohort Study (2002–2012)

Purpose: To examine the association of egg intake with 10-year risk of cardiovascular disease (CVD) and other cardiometabolic risk factors in a sample of individuals of Mediterranean origin. Methods: In 2001–2002, n = 1514 men and n = 1528 women (>18 years old) from the greater Athens area, Greece, were enrolled. Information on any egg intake, eaten as a whole, partly or in recipes was assessed via a validated semi-quantitative food frequency questionnaire. Follow-up for CVD evaluation (2011–2012) was achieved in n = 2020 participants (n = 317 CVD cases). Results: Ranking from lowest (<1 serving/week) to intermediate (1–4 servings/week) and high (4–7 servings/week) egg consumption tertiles, lower CVD incidence was observed (18%, 9% and 8%, respectively, p-for-trend = 0.004). Unadjusted analysis revealed that 1–3 eggs/week and 4–7 eggs/week were associated with a 60% and 75%, respectively, lower risk of developing CVD compared with the reference group (<1 egg/week). When adjusting for sociodemographic, lifestyle and clinical factors, significance was retained only for 1–3 eggs/week (hazard ratio (HR) = 0.53, 95% confidence interval (95% CI) = 0.28, 1.00). When total saturated fatty acid (SFA) intake was taken into account, this inverse association was non-significant. Multi-adjusted analysis revealed that in participants of low SFA intake, 1 serving/day increase in egg intake resulted in 45% lower risk of developing CVD. In the case of higher SFA consumption, only 1–3 eggs/week seemed to protect against CVD (HR = 0.25, 95% CI = 0.07, 0.86). In the case of intermediate cardiometabolic disorders, no significant trend was observed. Conclusions: Overall dietary habits principally in terms of SFA intake may be detrimental to define the role of eggs in cardiac health.     

Mediterranean Diet and Fatty Liver Risk in a Population of Overweight Older Italians: A Propensity Score-Matched Case-Cohort Study

Hepatic steatosis, often known as fatty liver, is the most common hepatic disease in Western countries. The latest guidelines for the treatment of nonalcoholic fatty liver disease emphasize lifestyle measures, such as changing unhealthy eating patterns. Using a propensity score-matching approach, this study investigated the effect of adhering to a Mediterranean diet (MedDiet) on fatty liver risk in an older population (≥65 years) from Southern Italy. We recruited 1.403 subjects (53.6% men, ≥65 years) who completed a food frequency questionnaire (FFQ) and underwent clinical assessment between 2015 and 2018. For the assessment of the liver fat content, we applied the Fatty Liver Index (FLI). To evaluate the treatment effect of the MedDiet, propensity score matching was performed on patients with and without FLI > 60. After propensity score-matching with the MedDiet pattern as treatment, we found a higher consumption of red meat (p = 0.04) and wine (p = 0.04) in subjects with FLI > 60. Based on the FLI, the inverse association shown between adherence to the MedDiet and the risk of hepatic steatosis shows that the MedDiet can help to prevent hepatic steatosis. Consuming less red and processed meat, as well as alcoholic beverages, may be part of these healthy lifestyle recommendations.     

Changes in Biomarkers of Non-Alcoholic Fatty Liver Disease (NAFLD) upon Access to Avocados in Hispanic/Latino Adults: Secondary Data Analysis of a Cluster Randomized Controlled Trial

Non-alcoholic fatty liver disease (NAFLD) is a public health concern and Hispanic/Latinos are disproportionately affected. There is evidence for favorable effects of dietary intake of monounsaturated fatty acids (MUFA) on NAFLD, yet studies examining avocados as a source of MUFA on hepatic function have not been assessed. We investigated the effects of low (3) vs. high (14) avocado allotment on biomarkers of NAFLD, oxidative stress, and NAFLD fibrosis score in a sample of Hispanic/Latino adults. Primary outcomes include hepatic function biomarkers [gamma glutamyltransferase (GGT), high-sensitivity c-reactive protein (hsCRP), and NAFLD fibrosis score]. Unpaired, two-sided t-tests were used to assess mean differences between intervention groups at 6 months and analysis of covariance models were used to adjust for diet quality and change in avocado intake from baseline to 6 months. Multivariable linear regression models evaluated the baseline and post-intervention association between avocado allotment group and outcomes, adjusting for covariates and stratifying by prediabetes status. No statistically significant differences were observed between low and high avocado allotment groups in liver enzymes, GGT, hsCRP or NAFLD fibrosis score. Findings persisted after stratifying by prediabetes status. Varied intake of avocados resulted in no effects on biomarkers of NAFLD in healthy adults, free of severe chronic disease.     

Cutoff Points of Waist Circumference for Predicting Incident Non-Alcoholic Fatty Liver Disease in Middle-Aged and Older Korean Adults

This study aimed to determine the optimal cutoff value of waist circumference (WC) for predicting incident NAFLD. In this community-based prospective cohort study, we analyzed data from 5400 participants without NAFLD at baseline aged 40–69 years. NAFLD was defined as a NAFLD-liver fat score >−0.640. A Cox proportional hazards regression model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for an association between body composition and NAFLD incidence. The predictive power of each body composition indicator was assessed by Harrell’s concordance index for Cox models. During a mean follow-up period of 12 years, there were 2366 new-onset NAFLD events. Compared with men with WC < 81 cm, the adjusted HR (95% CI) for incident NAFLD in those with WC ≥ 81 cm was 2.44 (2.23–2.67). Compared with women with WC < 78.5 cm, the adjusted HR (95% CI) for incident NAFLD in those with WC ≥ 78.5 cm was 2.54 (2.25–2.87). WC was the most significant risk factor for predicting incident NAFLD among body composition indicators in middle-aged and older Korean adults. The optimal WC cutoff point for predicting incident NALFD was 81 cm in men and 78.5 cm in women, which might assist in the early detection and prevention of NAFLD.     

Impact of Physical Activity Differences Due to COVID-19 Pandemic Lockdown on Non-Alcoholic Fatty Liver Parameters in Adults with Metabolic Syndrome

Background: A Mediterranean lifestyle with a Mediterranean diet and regular physical activity (PA) improves metabolic syndrome (MetS) characteristics and non-alcoholic fatty liver disease (NAFLD). The COVID-19 pandemic stopped healthy habits and increased NAFLD progression. Objectives: To assess how PA differences due to COVID-19 lockdown affected NAFLD parameters in adults with MetS. Design: Longitudinal 2-year analysis of data obtained between COVID-19 pre- and post-lockdown in a parallel-group randomized trial (n = 57, aged 40–60 years old, with MetS and NAFLD). Methods: NAFLD status and related parameters were assessed by magnetic resonance imaging (MRI), blood collection analysis and related indexes. PA and fitness status were assessed by an Alpha-Fit test battery, accelerometers, validated Minnesota questionnaire and functional fitness score. During lockdown, study personnel telephoned patients to motivate them. Participants were grouped according to PA levels. Results: The low PA group improved its fitness score tests (0.2) after lockdown more than the medium PA group, and it decreased its sedentary activity (−48.7 min/day), increased light (20.9 min/day) and moderate (32.3 min/day) PA intensities and improved sleep efficiency (0.6%) in comparison with the medium and high PA groups. The high PA group increased its steps per day more than the other groups. The low PA group was the only group that decreased its gamma glutamyl transferase (GGT) levels (−17.0 U/L). All groups increased their fatty liver index (FLI) after lockdown, but the medium PA group increased its FLI more than the low PA group. Participants in the high PA group decreased their HDL-cholesterol levels more than participants in the medium PA group (−0.4 mg/dL). Conclusions: Stopping regular PA together with an unhealthy lifestyle leads to a worsening of MetS and NAFLD. COVID-19 lockdown induced a decrease in PA in more active people, but inactive people increased their PA levels. Motivation seemed to be very important during lockdown.     

Low-Density Lipoprotein Receptor-Related Protein 6 (LRP6) Is a Novel Nutritional Therapeutic Target for Hyperlipidemia,Non-Alcoholic Fatty Liver Disease,and Atherosclerosis

Low-density lipoprotein receptor-related protein 6 (LRP6) is a member of the low-density lipoprotein receptor family and has a unique structure, which facilitates its multiple functions as a co-receptor for Wnt/β-catenin signaling and as a ligand receptor for endocytosis. The role LRP6 plays in metabolic regulation, specifically in the nutrient-sensing pathway, has recently garnered considerable interest. Patients carrying an LRP6 mutation exhibit elevated levels of LDL cholesterol, triglycerides, and fasting glucose, which cooperatively constitute the risk factors of metabolic syndrome and atherosclerosis. Since the discovery of this mutation, the general role of LRP6 in lipid homeostasis, glucose metabolism, and atherosclerosis has been thoroughly researched. These studies have demonstrated that LRP6 plays a role in LDL receptor-mediated LDL uptake. In addition, when the LRP6 mutant impaired Wnt-LRP6 signaling, hyperlipidemia, non-alcoholic fatty liver disease, and atherosclerosis developed. LRP6 regulates lipid homeostasis and body fat mass via the nutrient-sensing mechanistic target of the rapamycin (mTOR) pathway. Furthermore, the mutant LRP6 triggers atherosclerosis by activating platelet-derived growth factor (PDGF)-dependent vascular smooth muscle cell differentiation. This review highlights the exceptional opportunities to study the pathophysiologic contributions of LRP6 to metabolic syndrome and cardiovascular diseases, which implicate LRP6 as a latent regulator of lipid metabolism and a novel therapeutic target for nutritional intervention.     

Salvia plebeia R. Br. Water Extract Ameliorates Hepatic Steatosis in a Non-Alcoholic Fatty Liver Disease Model by Regulating the AMPK Pathway

Salvia plebeia R. Br. (SP), grown from autumn to spring, is used as a medicinal herb from roots to leaves. This herb exhibits antioxidant activities and various physiological effect, including anti-asthma, immune-promoting, anti-obesity, and anti-cholesterol effects. However, the effectiveness of SP against non-alcoholic fatty liver disease (NAFLD) and the associated mechanism have not been elucidated. In this study, alleviation of NAFLD by SP was confirmed in a mouse model of hepatic steatosis induced by a high-fat diet and in HepG2 cells administered free fatty acids (FFA). In the experimental model, intrahepatic lipid accumulation was investigated using the AdipoRed^TM assay, Oil Red O staining, biomarker analysis, and hematoxylin and eosin staining. Furthermore, glucose tolerance was examined based on the fasting glucose levels and oral glucose tolerance. The molecular mechanisms related to hepatic steatosis were determined based on marker mRNA levels. Blood FFAs were found to flow into the liver via the action of fatty acid translocase, cluster of differentiation 36, and fatty acid transporter proteins 2 and 5. Salvia plebeia R. Br. water extract (SPW) suppressed the FFAs inflow by regulating the expression of the above-mentioned proteins. Notably, modulating the expression of AMP-activated protein kinase (AMPK) and liver X receptor, which are involved in the regulation of lipid metabolism, stimulated peroxisome proliferator activated receptor α in the nucleus to induce the expression genes involved in β-oxidation and increase β-oxidation in the mitochondria. AMPK modulation also increased the expression of sterol regulatory element binding protein-1c, which activated lipid synthesis enzymes. As a consequence of these events, triglyceride synthesis was reduced and lipid accumulation in hepatocytes was alleviated. Overall, our findings suggested that SPW could ameliorate NAFLD by inhibiting hepatic steatosis through AMPK modulation.     

Dietary Fructose Reduction Improves Markers of Cardiovascular Disease Risk in Hispanic-American Adolescents with NAFLD

Nonalcoholic fatty liver disease (NAFLD) is now thought to be the most common liver disease worldwide. Cardiovascular complications are a leading cause of mortality in NAFLD. Fructose, a common nutrient in the westernized diet, has been reported to be associated with increased cardiovascular risk, but its impact on adolescents with NAFLD is not well understood. We designed a 4-week randomized, controlled, double-blinded beverage intervention study. Twenty-four overweight Hispanic-American adolescents who had hepatic fat >8% on imaging and who were regular consumers of sweet beverages were enrolled and randomized to calorie-matched study-provided fructose only or glucose only beverages. After 4 weeks, there was no significant change in hepatic fat or body weight in either group. In the glucose beverage group there was significantly improved adipose insulin sensitivity, high sensitivity C-reactive protein (hs-CRP), and low-density lipoprotein (LDL) oxidation. These findings demonstrate that reduction of fructose improves several important factors related to cardiovascular disease despite a lack of measurable improvement in hepatic steatosis. Reducing dietary fructose may be an effective intervention to blunt atherosclerosis progression among NAFLD patients and should be evaluated in longer term clinical trials.     

Lactiplantibacillus plantarum DSM20174 Attenuates the Progression of Non-Alcoholic Fatty Liver Disease by Modulating Gut Microbiota,Improving Metabolic Risk Factors,and Attenuating Adipose Inflammation

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease, reaching epidemic proportions worldwide. Targeting the gut–adipose tissue–liver axis by modulating the gut microbiota can be a promising therapeutic approach in NAFLD. Lactiplantibacillus plantarum, a potent lactic-acid-producing bacterium, has been shown to attenuate NAFLD. However, to our knowledge, the possible effect of the Lactiplantibacillus plantarum strain DSM20174 (L.p. DSM20174) on the gut–adipose tissue axis, diminishing inflammatory mediators as fuel for NAFLD progression, is still unknown. Using a NAFLD mouse model fed a high-fat, high-fructose (HFHF) diet for 10 weeks, we show that L.p DSM20174 supplementation of HFHF mice prevented weight gain, improved glucose and lipid homeostasis, and reduced white adipose inflammation and NAFLD progression. Furthermore, 16S rRNA gene sequencing of the faecal microbiota suggested that treatment of HFHF-fed mice with L.p DSM20174 changed the diversity and altered specific bacterial taxa at the levels of family, genus, and species in the gut microbiota. In conclusion, the beneficial effects of L.p DSM20174 in preventing fatty liver progression may be related to modulations in the composition and potential function of gut microbiota associated with lower metabolic risk factors and a reduced M1-like/M2-like ratio of macrophages and proinflammatory cytokine expression in white adipose tissue and liver.