Non-alcoholic Liver Steatosis Research Articles

A Nutritional Education Could Prevent Non-alcoholic Fatty Liver Steatosis Linked to Obesity in Morocco

A Nutritional Education Could Prevent Non-alcoholic Fatty Liver Steatosis Linked to Obesity in Morocco

Hybrid Quantum Image Classification and Federated Learning for Hepatic Steatosis Diagnosis.

In the realm of liver transplantation, accurately determining hepatic steatosis levels is crucial. Recognizing the essential need for improved diagnostic precision, particularly for optimizing diagnosis time by swiftly handling easy-to-solve cases and allowing the expert time to focus on more complex cases, this study aims to develop cutting-edge algorithms that enhance the classification of liver biopsy images. Additionally, the challenge of maintaining data privacy arises when creating automated algorithmic solutions, as sharing patient data between hospitals is restricted, further complicating the development and validation process. This research tackles diagnostic accuracy by leveraging novel techniques from the rapidly evolving field of quantum machine learning, known for their superior generalization abilities. Concurrently, it addresses privacy concerns through the implementation of privacy-conscious collaborative machine learning with federated learning. We introduce a hybrid quantum neural network model that leverages real-world clinical data to assess non-alcoholic liver steatosis accurately. This model achieves an image classification accuracy of 97%, surpassing traditional methods by 1.8%. Moreover, by employing a federated learning approach that allows data from different clients to be shared while ensuring privacy, we maintain an accuracy rate exceeding 90%. This initiative marks a significant step towards a scalable, collaborative, efficient, and dependable computational framework that aids clinical pathologists in their daily diagnostic tasks.

Transplantation of beige adipose organoids fabricated using adipose acellular matrix hydrogel improves metabolic dysfunction in high-fat diet-induced obesity and type 2 diabetes mice.

Transplantation of brown adipose tissue (BAT) is a promising approach for treating obesity and metabolic disorders. However, obtaining sufficient amounts of functional BAT or brown adipocytes for transplantation remains a major challenge. In this study, we developed a hydrogel that combining adipose acellular matrix (AAM) and GelMA and HAMA that can be adjusted for stiffness by modulating the duration of light-crosslinking. We used human white adipose tissue-derived microvascular fragments to create beige adipose organoids (BAO) that were encapsulated in either a soft or stiff AAM hydrogel. We found that BAOs cultivated in AAM hydrogels with high stiffness demonstrated increased metabolic activity and upregulation of thermogenesis-related genes. When transplanted into obese and type 2 diabetes mice, the HFD + BAO group showed sustained improvements in metabolic rate, resulting in significant weight loss and decreased blood glucose levels. Furthermore, the mice showed a marked reduction in nonalcoholic liver steatosis, indicating improved liver function. In contrast, transplantation of 2D-cultured beige adipocytes failed to produce these beneficial effects. Our findings demonstrate the feasibility of fabricating beige adipose organoids in vitro and administering them by injection, which may represent a promising therapeutic approach for obesity and diabetes.

Endoplasmic Reticulum Protein TXNDC5 Interacts with PRDX6 and HSPA9 to Regulate Glutathione Metabolism and Lipid Peroxidation in the Hepatic AML12 Cell Line.

Non-alcoholic fatty liver disease or steatosis is an accumulation of fat in the liver. Increased amounts of non-esterified fatty acids, calcium deficiency, or insulin resistance may disturb endoplasmic reticulum (ER) homeostasis, which leads to the abnormal accumulation of misfolded proteins, activating the unfolded protein response. The ER is the primary location site for chaperones like thioredoxin domain-containing 5 (TXNDC5). Glutathione participates in cellular oxidative stress, and its interaction with TXNDC5 in the ER may decrease the disulfide bonds of this protein. In addition, glutathione is utilized by glutathione peroxidases to inactivate oxidized lipids. To characterize proteins interacting with TXNDC5, immunoprecipitation and liquid chromatography-mass spectrometry were used. Lipid peroxidation, reduced glutathione, inducible phospholipase A2 (iPLA2) and hepatic transcriptome were assessed in the AML12 and TXNDC5-deficient AML12 cell lines. The results showed that HSPA9 and PRDX6 interact with TXNDC5 in AML12 cells. In addition, TXNDC5 deficiency reduced the protein levels of PRDX6 and HSPA9 in AML12. Moreover, lipid peroxidation, glutathione and iPLA2 activities were significantly decreased in TXNDC5-deficient cells, and to find the cause of the PRDX6 protein reduction, proteasome suppression revealed no considerable effect on it. Finally, hepatic transcripts connected to PRDX6 and HSPA9 indicated an increase in the Dnaja3, Mfn2 and Prdx5 and a decrease in Npm1, Oplah, Gstp3, Gstm6, Gstt1, Serpina1a, Serpina1b, Serpina3m, Hsp90aa1 and Rps14 mRNA levels in AML12 KO cells. In conclusion, the lipid peroxidation system and glutathione mechanism in AML12 cells may be disrupted by the absence of TXNDC5, a novel protein-protein interacting partner of PRDX6 and HSPA9.

Early diagnosis of non-alcoholic fatty liver disease: the role of biomarkers and complex indices of non-alcoholic fatty liver steatosis

Metabolic syndrome is a series of pathologies united by a similar pathogenesis, the end of which, most often, is cardiovascular accidents, which are leaders among the causes of death in the population around the world. Non-alcoholic fatty liver disease (NAFLD) is the hepatic equivalent of the metabolic syndrome, registered earlier than all other equivalents, on the rights of the liver as a first-line energy depot. At the same time, according to multicenter studies, 95% of people with NAFLD (any stage) are not diagnosed with the disease. Clarification of additional risk factors for NAFLD and the presence of a specific biomarker of non-alcoholic liver steatosis would make it possible to stop the vicious cascade of metabolic processes, which in the future can lead to a significant increase in the life expectancy of the population. The potentially high role of Secreted Frizzled Related Protein-4 (SFRP4) adipokine in the early diagnosis of NAFLD is known. The aim of the study was to optimize the early diagnosis of non-alcoholic fatty liver disease using modern indices and biomarkers. Materials and methods. The work was carried out at the Department of Faculty and Hospital Therapy of the Chuvash State University named after I. N. Ulyanov” in the period from 2016 to 2020. This study included several stages: first of all, a retrospective analysis of 1150 outpatient records of patients from several medical organizations of the Chuvash Republic for the period 2016-2018 was carried out. to form two study groups: experimental and control. At the second stage, as a result of applying the exclusion criteria, 162 people remained in the experiment: 110 from the experimental group, 52 from the control group. The subjects of both groups were compared by gender and age, the age range of the subjects varied from 18 to 80 years old with an average value of 48.3 years. Further, the patients undergo a detailed examination, according to the presented plan: Collection of complaints, medical history, objective examination. Laboratory studies (general and biochemical blood tests, lipidogram, assessment of the level of serum adipokine SFRP4). Instrumental studies (ultrasound of the OBP, TE (SAR), ESP with elastometry). Evaluation of the most informative complex indices for the early diagnosis of NAFLD: MI, IVO indices, HSI, FLD-I. Further, all the necessary statistical processing and analysis of the obtained data were performed (Microsoft Office Excel 2016, StatTech v. 2.8.8 (developer - Stattech LLC, Russia)). Results. Accessible (not requiring the use of additional time and material costs) NAFLD indices with the highest sensitivity rates (99.1% and 98.2%, respectively) were MI and IVO. A noticeable direct correlation was traced between MI (p=0.640), moderate - between the IVO (p=0.398) and the elastographically determined index of non-alcoholic liver steatosis. High sensitivity and specificity of skin manifestations (xanthoma, xanthelasma - 69.6% and 89.7% and seborrheic dermatitis - 82.0% and 71.4%) were found in relation to early manifestations of NAFLD. From anthropometric indicators: the CW/CF index has a pronounced (ρ=0.643), CW - moderate (ρ=0.238), and BMI - a weak direct (ρ=0.223) correlation with the elastographically determined index of non-alcoholic liver steatosis. Adipokine SFRP4 correlates (ρ=0.841) with early manifestations of hepatic steatosis in patients, as determined by TE in CAP mode.

Measured vs estimated resting energy expenditure in children and adolescents with obesity

Pediatric obesity requires early targeted interventions consisting mainly of a low-calorie diet prescribed based on resting energy expenditure (REE), often estimated through predictive equations. The aim of this study was to define the prevalence of "hypo-", "normo-" and "hypermetabolic" in a large cohort of children and adolescents with obesity by comparing measured and estimated REE and to evaluate the characteristics related to these metabolic statuses in both males and females. The study population was divided into the three subgroups by comparing REE measured using indirect calorimetry and estimated using the Molnar equation, and subsequently analyzed. The majority of the participants (60.6%) were normometabolic, 25.5% hypermetabolic and 13.9% hypometabolic. No significant differences in age, Tanner stage, systolic blood pressure, or the presence of metabolic syndrome were found. However, the hypermetabolic subgroup was significantly lighter, shorter, with lower hip and waist circumferences, had a greater amount of fat-free mass and lower fat mass, significantly lower diastolic blood pressure, and a significantly higher frequency of non-alcoholic liver steatosis. Pediatric obesity is more associated with normal or increased REE than with a hypometabolic condition, suggesting that estimation of energy expenditure with predictive equations is still inadequate for prescribing the appropriate diet plan.

Clinical and laboratory features of the course of non-alcoholic liver steatosis in women in the early postmenopausal period living on the territory of an industrial megapolis

The aim. To study risk factors, clinical features, anthropometric, biochemical and metabolic parameters, parameters of the functional state of the endothelium, the level of interleukin-6 (IL-6) and markers of hemostasis in patients with non-alcoholic liver steatosis in the early postmenopausal period living in Perm. Materials and methods. 100 women in the early postmenopausal period were examined: 70 patients with the clinical form non-alcoholic liver steatosis and overweight or obesity of varying severity (49.9±1.1 years) and 30 practically healthy women without obesity and liver pathology (47.3±2.6 years). Biochemical parameters, lipid spectrum, insulin, leptin, leptin receptors, interleukin-6 (IL-6), markers of endothelial dysfunction, hemostasis parameters were determined in the blood of all subjects, body mass index (BMI), free leptin index, NOMA-IR and Caro were calculated. Liver steatosis was determined by ultrasound examination. Results. General weakness (35%), severity (35%) and pain (15%) in the right hypochondrium (35%), dyspepsia - belching (25%), nausea (15%), heartburn (10%), flatulence (10%). Hypertension was observed in 60% of women, type 2 diabetes mellitus - in 24%. All patients had a genoid type of obesity. 34% of women with non-alcoholic liver steatosis were overweight, 29% were obese of the 1st degree, 23% were obese of the 2nd degree, and 14% of patients were obese of the 3rd degree. Conclusion: In the examined women with non-alcoholic liver steatosis in the early postmenopausal period living in Perm, risk factors for the development of obesity were identified: consumption of high-calorie foods with high fat and sugar content and hypokinesia, and the course of the disease was accompanied by the development of dyslipidemia, insulin and leptin resistance, inflammatory syndrome with activation of proinflammatory cytokine IL-6 and hyperfibrinogenemia, and also endothelial dysfunction, the severity of which increased during the transition from 1 to 2-3 degrees of obesity.

The importance of vascular endothelial growth factor and polymorphism of the VEGF a gene (g634c) in the development of steatosis, fibrosis and cirrhosis of the liver patients in the city of Perm

Introduction. Chronic liver diseases are a significant medical problem all over the world. To date, there is a need to develop a set of laboratory tests, including genetic ones, to determine the risk of development and progression of steatosis, fibrosis and cirrhosis of the liver of various etiologies. Aim: To investigate the serum concentration of vasculoendothelial growth factor (VEGF) and the frequency of occurrence of VEGFA gene polymorphism genotypes in the region -634G/C (rs2010963) in patients with steatosis, fibrosis and cirrhosis of the liver in the Perm Region. Materials and methods: 258 people were examined, including 52 patients with non-alcoholic liver steatosis, 95 patients with chronic hepatitis C and liver fibrosis, 46 people with cirrhosis of the liver of viral (HCV) and alcoholic etiology and 65 practically healthy individuals. The serum concentration of VEGF was determined by enzyme immunoassay. Polymorphisms of the VEGFA gene in region -634G/C were analyzed by polymerase chain reaction. Result: The development of steatosis, fibrosis and cirrhosis of the liver is accompanied by endothelial damage with activation of neoangiogenesis due to hyperproduction of VEGF (p=0.001, p=0.0001 and p=0.001, respectively) in the blood serum. Elevated serum VEGF values in patients confirmed the presence of endothelial dysfunction in liver pathology. The study of the single nucleotide polymorphism of the VEGFA gene (G634C) showed a higher incidence of recessive allele C in patients with steatosis and cirrhosis in 54.81% (p=0.01) and 48.9% (p=0.04) of cases than in the control group -37.69%, which suggested the presence of an association of the carrier of allele C of this polymorphism in the form of genotypes CC or GC with a risk of developing steatosis and cirrhosis of the liver. Conclusion. Determination of the genetic marker VEGFA in the region -634G/C allows us to assess the increased risk of developing chronic liver diseases when exposed to various etiological factors.

Association of nutrient intake with non-alcoholic fatty liver disease and liver steatosis in adult Indian population – A case control study

Association of nutrient intake with non-alcoholic fatty liver disease and liver steatosis in adult Indian population – A case control study

Waist Circumference as a Risk Factor for Non-Alcoholic Fatty Liver Disease in Older Adults in Guayaquil, Ecuador.

A cross-sectional study was carried out in 99 older adults who regularly attended five gerontological centers in the city of Guayaquil, Ecuador. The variables studied were age, gender, independent life, access to complete meals, waist circumference, and NAFLD diagnosed by ultrasound. A significant relationship exists between waist circumference, body mass index, and fat mass percentage. However, only age and waist circumference were significant in the multivariate logistic regression model. Our results suggest that in the presence of waist circumference, body mass index loses its significance and age may be a protective factor due to adipose tissue loss and redistribution. Anthropometric measurements such as waist circumference can be used as complement indicators of NAFLD.

Korelacija FLI indeksa masne jetre sa indeksima insulinske rezistencije kod pacijenata sa metaboličkim sindromom

Introduction: Metabolic syndrome includes insulin resistance, visceral obesity, hypertension and dyslipidemia, which together lead to an increased risk of atherosclerosis, cardiovascular diseases, and diabetes mellitus. Insulin resistance is considered a pathophysiological mechanism underlying metabolic syndrome, characterized by inadequate glucose metabolism, hyperinsulinemia and lipid imbalance. Non-alcoholic fatty liver disease is a chronic disease characterized by microvesicular steatosis and isn't a consequence of the use of drugs, alcohol, or inherited diseases and is a hepatic manifestation of metabolic syndrome. Aim: Since insulin resistance is pathophysiologically related to metabolic liver diseases, the aim of this study was to investigate the correlation of the FLI index with insulin resistance indices HOMA and QUICKI, but also a comparison of the insulin resistance index HOMA, Quicki and Tyg and the FLI index of fatty liver in the complete sample and in the groups of overweight and obese patients with characteristics of the metabolic syndrome. Material and methods: The study included 70 patients who met the criteria for the diagnosis of metabolic syndrome and who were selected by reviewing the medical documentation. Patients were divided into two groups. Group A were overweight patients (BMI 25 - 29.9 kg/m2). Group B were obese patients (BMI > 30 kg/m2). Insulin resistance index values were compared between groups and then correlated by statistical analysis with FLI index within groups and in a complete sample. Results: Statistical analysis found a correlation between the FLI index and the insulin resistance index HOMA (p = 0.03) in a complete sample. A statistically significant difference in the values of the FLI index between the examined groups was proved (p = 0.001). Conclusion: The positive correlation between the FLI index with the HOMA index speaks in favor of the interrelationship between insulin resistance and fatty liver in patients with metabolic syndrome. In this case, insulin resistance can be a predictor for the development of non-alcoholic fatty liver disease, steatosis, steatohepatitis, hepatocellular carcinoma and cardiovascular diseases.

Berberine alleviates non-alcoholic hepatic steatosis partially by promoting SIRT1 deacetylation of CPT1A in mice.

Berberine effectively alleviates non-alcoholic fatty liver disease (NAFLD). Nevertheless, the mechanism is incompletely comprehended. It has been reported that SIRT1 mediates lipid metabolism in liver and berberine promotes the expression of SIRT1 in hepatocytes. We hypothesized that SIRT1 mediated the effect of berberine on NAFLD. The effects of berberine on NAFLD were evaluated in C57BL/6J mice fed a high-fat diet (HFD) and in mouse primary hepatocytes and cell lines exposed to palmitate. The change of fatty acid oxidation (FAO) and the activity of CPT1A were observed in HepG2 cells. Quantitative real-time polymerase chain reaction and Western blot were employed to observe the expression of SIRT1 and lipid metabolism-related molecules. The interaction between SIRT1 and CPT1A was investigated by using co-immunoprecipitation assay in HEK293T cells. Berberine treatment attenuated hepatic steatosis, reduced triglyceride (190.1 ± 11.2 μmol/g liver vs 113.6 ± 7.6 μmol/g liver, P < 0.001) and cholesterol (11.3 ± 2.5 μmol/g liver vs 6.3 ± 0.4 μmol/g liver, P < 0.001) concentration in the liver, and improved lipid and glucose metabolism disorders compared with the HFD group. The expression of SIRT1 was reduced in the liver of NAFLD patients and mouse models. Berberine increased the expression of SIRT1 and promoted the protein level of CPT1A and its activity in HepG2 cells. SIRT1 overexpression mimicked the effect of berberine on reducing triglyceride levels in HepG2 cells, whereas SIRT1 knock-down attenuated the effect of berberine. Mechanistically, berberine increased the expression of SIRT1. SIRT1 deacetylated CPT1A at the Lys675 site, which suppressed its ubiquitin-dependent degradation, thereby promoting FAO and alleviating non-alcoholic liver steatosis. Berberine promoted SIRT1 deacetylation of CPT1A at the Lys675 site, which reduced the ubiquitin-dependent degradation of CPT1A and ameliorated non-alcoholic liver steatosis.

Experimental study of the hepatoprotective effect of the aqueous extract of Jinura Procumbens leaves on the model of fructose-induced non-alcoholic liver steatosis

The aim. To study the hepatoprotective effect of the aqueous extract of the leaves of Gynura Procumbens (GP) on an experimental model of fructose-induced non-alcoholic liver steatosis in laboratory animals. Materials and methods. The experimental study was conducted for 30 days on 25 non-inbred sexually mature white male rats aged 8-9 months, weighing 400-530 g., which comprised 3 groups: “Control” (received a full-fledged balanced standard granular feed), “fructose-induced steatosis” (feeding was carried out similarly to animals of the first group using a 15% solution of fructose as drinking water) and “Steatosis + GP” (simulated liver steatosis and simultaneously daily intragastric daily administration of GP leaf extract was performed. Laboratory parameters (transaminases, glucose and lipid spectrum) in blood serum, biometric indicators (animal mass, liver mass and mass coefficient) and histological examination of the liver were studied in all animals according to the conclusion from the experiment. Results. The course of fructose-induced liver steatosis in experimental animals is accompanied by lipid spectrum disorders, hepatomegaly without the formation of general obesity and morphological changes in liver tissue in the form of fatty degeneration without signs of inflammation and fibrosis. Conclusion: The course intragastric administration of an aqueous extract of GP leaves to experimental animals with steatosis does not significantly affect the lipid spectrum, but prevents the formation of hepatomegaly and morphological changes characteristic of steatosis in liver tissue.

Features of the course of non-alcoholic liver steatosis in women of reproductive age and in menopause

Introduction. Non-alcoholic fatty liver disease (NAFLD) increases with age. The main risk factor for NAFLD and the progression of liver fibrosis is obesity. However, the disease also occurs in 7% of people with normal body weight, mainly in young women with normal levels of liver enzymes, in whom liver disease can nevertheless progress.Aim. To assess the features of clinical and laboratory manifestations of non-alcoholic hepatic steatosis (NASP) in women of reproductive age and in menopause, depending on the degree of obesity.Materials and methods. We examined 86 women with NAS and obesity, of which 49 were women of reproductive age (37.3 ± 1.7 years) and 37 patients in menopause (51.3 ± 1.0 years). Determined: transaminases, total bilirubin, glucose, lipid spectrum, insulin, leptin, interleukin-6 (IL-6), vasculoendothelial growth factor (VEGF); body mass index (BMI), atherogenicity index (AI), and HOMA-IR index were calculated. Liver steatosis was determined by ultrasound, fibrosis was excluded by fibroelastography.Results. The clinic in both groups of women was poor; there were no signs of liver fibrosis. In women with liver steatosis with concomitant obesity in reproductive age and menopause, dyslipidemia, hyperleptinemia, increased levels of IL-6 and signs of endothelial damage in the form of VEGF hyperproduction are recorded. At the same time, dyslipidemia and hyperleptinemia are significant in menopause, and in women with steatosis at reproductive age, signs of endothelial damage are more pronounced.Conclusion. In both groups of women with the clinical form of NASP, most of the studied laboratory parameters marked the transition to stage 1 obesity, leptin made it possible to differentiate almost all degrees of obesity, and the production of IL-6 and VEGF significantly increased at stages 2–3 of obesity.

Characteristics of lipid spectrum and functional liver tests in patients with nonalcoholic liver steatosis depending on degree of obesity during menopause

Objective. To study the blood lipid spectrum and functional liver tests in women with nonalcoholic liver steatosis (NALS) depending on the degree of obesity during menopause.&#x0D; Materials and methods. Seventy patients with NALS and obesity (NALS-O-M) in menopause with the mean age of 49,9 1,1 years including 24 with increased body mass index (BMI), 20 with the degree 1 obesity, 18 the degree 2 obesity and 8 the degree 3 obesity were examined. The control group involved 30 practically healthy women in menopause without obesity. Blood serum cytolysis, cholestasis and lipid spectrum indicators were studied in both groups.&#x0D; Results. According to the results of biochemical investigation, in the group of patients with NALS-O-M syndrome no cytolysis was observed. In case of marked obesity, cholestasis syndrome by the blood alkaline phosphatase level was identified. Lipid spectrum in patients with NALS-O-M statistically significantly differed from the control: hypercholesterinemia, hypertriglyceridemia, increase in the low- and very low-density lipoproteins as well as calculated index of atherogeneity with decrease in the high-density lipoproteins fraction was registered.&#x0D; Conclusions. A pronounced obesity causes the cholestasis syndrome with an increase in the blood alkaline phosphatase level. Dyslipidemia of different degree of manifestation is registered in all patients with steatosis and obesity during menopause, being more marked in patients with the degree 23 obesity.

Parathyroid hormone alleviates non-alcoholic liver steatosis via activating the hepatic cAMP/PKA/CREB pathway.

Non-alcoholic fatty liver disease (NAFLD), hallmarked by liver steatosis, is becoming a global concern, but effective and safe drugs for NAFLD are still lacking at present. Parathyroid hormone (PTH), the only FDA-approved anabolic treatment for osteoporosis, is important in calcium-phosphate homeostasis. However, little is known about its potential therapeutic effects on other diseases. Here, we report that intermittent administration of PTH ameliorated non-alcoholic liver steatosis in diet-induced obese (DIO) mice and db/db mice, as well as fasting-induced hepatic steatosis. In vitro, PTH inhibits palmitic acid-induced intracellular lipid accumulation in a parathyroid hormone 1 receptor (PTH1R)-dependent manner. Mechanistically, PTH upregulates the expression of genes involved in lipid β-oxidation and suppresses the expression of genes related to lipid uptake and de novo lipogenesis by activating the cAMP/PKA/CREB pathway. Taken together, our current finding proposes a new therapeutic role of PTH on NAFLD.

Association postprandial hypertriglyceridemia, carotid intima-media thickness and body mass index in patients with coronary artery disease combined with nonalcoholic liver steatosis

Background and Aims : To estimate the frequency of postprandial hypertriglyceridemia (PPG), carotid intima-media thickness and body mass index (BMI) in patients with coronary artery disease (CHD) combined with nonalcoholic liver steatosis (NALS).

Insulin resistance, level of leptin and body mass index in patients with coronary artery disease combined with nonalcoholic liver steatosis

Background and Aims : To estimate the frequency of insulinresistance (IR), level of leptin and body mass index (BMI) in patients with coronary artery disease (CHD) combined with nonalcoholic liver steatosis (NALS).

Reduction of De Novo Lipogenesis Mediates Beneficial Effects of Isoenergetic Diets on Fatty Liver: Mechanistic Insights from the MEDEA Randomized Clinical Trial.

Background: Non-alcoholic liver steatosis (NAS) results from an imbalance between hepatic lipid storage, disposal, and partitioning. A multifactorial diet high in fiber, monounsaturated fatty acids (MUFAs), n-6 and n-3 polyunsaturated fatty acids (PUFAs), polyphenols, and vitamins D, E, and C reduces NAS in people with type 2 diabetes (T2D) by 40% compared to a MUFA-rich diet. We evaluated whether dietary effects on NAS are mediated by changes in hepatic de novo lipogenesis (DNL), stearoyl-CoA desaturase (SCD1) activity, and/or β-oxidation. Methods: According to a randomized parallel group study design, 37 individuals with T2D completed an 8-week isocaloric intervention with a MUFA diet (n = 20) or multifactorial diet (n = 17). Before and after the intervention, liver fat content was evaluated by proton magnetic resonance spectroscopy, serum triglyceride fatty acid concentrations measured by gas chromatography, plasma β-hydroxybutyrate by enzymatic method, and DNL and SCD-1 activity assessed by calculating the palmitic acid/linoleic acid (C16:0/C18:2 n6) and palmitoleic acid/palmitic acid (C16:1/C16:0) ratios, respectively. Results: Compared to baseline, mean ± SD DNL significantly decreased after the multifactorial diet (2.2 ± 0.8 vs. 1.5 ± 0.5, p = 0.0001) but did not change after the MUFA diet (1.9 ± 1.1 vs. 1.9 ± 0.9, p = 0.949), with a significant difference between the two interventions (p = 0.004). The mean SCD-1 activity also decreased after the multifactorial diet (0.13 ± 0.05 vs. 0.10 ± 0.03; p = 0.001), but with no significant difference between interventions (p = 0.205). Fasting plasma β-hydroxybutyrate concentrations did not change significantly after the MUFA or multifactorial diet. Changes in the DNL index significantly and positively correlated with changes in liver fat (r = 0.426; p = 0.009). Conclusions: A diet rich in multiple beneficial dietary components (fiber, polyphenols, MUFAs, PUFAs, and other antioxidants) compared to a diet rich only in MUFAs further reduces liver fat accumulation through the inhibition of DNL. Registered under ClinicalTrials.gov no. NCT03380416.

Exposure to per- and Polyfluoroalkyl Substances and Markers of Liver Injury: A Systematic Review and Meta-Analysis.

Background:Experimental evidence indicates that exposure to certain pollutants is associated with liver damage. Per- and polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals widely used in industry and consumer products and bioaccumulate in food webs and human tissues, such as the liver.Objective:The objective of this study was to conduct a systematic review of the literature and meta-analysis evaluating PFAS exposure and evidence of liver injury from rodent and epidemiological studies.Methods:PubMed and Embase were searched for all studies from earliest available indexing year through 1 December 2021 using keywords corresponding to PFAS exposure and liver injury. For data synthesis, results were limited to studies in humans and rodents assessing the following indicators of liver injury: serum alanine aminotransferase (ALT), nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, or steatosis. For human studies, at least three observational studies per PFAS were used to conduct a weighted -score meta-analysis to determine the direction and significance of associations. For rodent studies, data were synthesized to qualitatively summarize the direction and significance of effect.Results:Our search yielded 85 rodent studies and 24 epidemiological studies, primarily of people from the United States. Studies focused primarily on legacy PFAS: perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexanesulfonic acid. Meta-analyses of human studies revealed that higher ALT levels were associated with exposure to PFOA ( 6.20, ), PFOS ( 3.55, ), and PFNA ( 2.27, ). PFOA exposure was also associated with higher aspartate aminotransferase and gamma-glutamyl transferase levels in humans. In rodents, PFAS exposures consistently resulted in higher ALT levels and steatosis.Conclusion:There is consistent evidence for PFAS hepatotoxicity from rodent studies, supported by associations of PFAS and markers of liver function in observational human studies. This review identifies a need for additional research evaluating next-generation PFAS, mixtures, and early life exposures. https://doi.org/10.1289/EHP10092