Nonalcoholic Hepatic Steatosis Research Articles

Sesamin ameliorates nonalcoholic hepatic steatosis by inhibiting CD36-mediated hepatocyte lipid accumulation in vitro and in vivo

Hepatic steatosis is a critical factor in the development of nonalcoholic steatohepatitis (NASH). Sesamin (Ses), a functional lignan isolated from Sesamum indicum, possesses hypolipidemic, liver-protective, anti-hypertensive, and anti-tumor properties. Ses has been found to improve hepatic steatosis, but the exact mechanisms through which Ses achieves this are not well understood. In this study, we observed the anti-hepatic steatosis effects of Ses in palmitate/oleate (PA/OA)-incubated primary mouse hepatocytes, AML12 hepatocytes, and HepG2 cells, as well as in high-fat, high-cholesterol diet-induced NASH mice. RNA sequencing analysis revealed that cluster of differentiation 36 (CD36), a free fatty acid (FA) transport protein, was involved in the Ses-mediated inhibition of hepatic fat accumulation. Moreover, the overexpression of CD36 significantly increased hepatic steatosis in both Ses-treated PA/OA-incubated HepG2 cells and NASH mice. Furthermore, Ses treatment suppressed insulin-induced de novo lipogenesis in HepG2 cells, which was reversed by CD36 overexpression. Mechanistically, we found that Ses ameliorated NASH by inhibiting CD36-mediated FA uptake and upregulation of lipogenic genes, including FA synthase, stearoyl-CoA desaturase 1, and sterol regulatory element-binding protein 1. The findings of our study provide novel insights into the potential therapeutic applications of Ses in the treatment of NASH.

Assessment of Non-Alcoholic Hepatic Steatosis Disease and its Association with Hepatomegaly by Using Ultrasound

Background: Non-alcoholic hepatic steatosis disease (NAHSD) is increasingly recognized as a major global health concern, particularly due to its silent progression and significant impact on quality of life. The prevalence of NAHSD is particularly high in regions with widespread obesity and diabetes, conditions that are escalating in global incidence. Objective: This study aimed to evaluate the prevalence and severity of NAHSD and its association with hepatomegaly using ultrasonography in a Pakistani adult population. Methods: A cross-sectional study was conducted from November 2023 to March 2024 at the Department of Radiology, District Head Quarter’s Hospital, Swabi, Pakistan. A total of 70 adults presenting with clinical manifestations of hepatomegaly were enrolled. Ultrasonography was performed using a Toshiba Doppler machine equipped with a convex transducer (2.5—5.0 MH frequency). Liver size, shape, and echogenicity were assessed, and hepatic parenchyma was graded into three categories based on echogenicity. Data were analyzed using SPSS version 25, focusing on descriptive and inferential statistics. Results: The study comprised 41 females (58.6%) and 29 males (41.4%), with an age range from 19 to 69 years (mean age 43.79 ± 11.583 years). Hepatic steatosis was graded as mild in 20% (14), moderate in 5.7% (4), and severe in 1.4% (1) of patients with hepatomegaly. The majority, 72.9% (51), showed no signs of hepatic steatosis. Hepatomegaly was noted in 27% of patients (19). Conclusion: Ultrasonography is an effective diagnostic tool for assessing NAHSD and hepatomegaly, revealing a significant prevalence of these conditions among the studied population. Early screening and intervention are critical to managing and reducing the healthcare burden associated with NAHSD.

Sonographic Association between Hepatic Steatosis Disease and Polycystic Ovarian Syndrome in Swabi Women

Background: Polycystic Ovarian Syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive age, with significant implications for their fertility and metabolic health. Non-Alcoholic Hepatic Steatosis Disease (NAHSD), or fatty liver disease, has been increasingly recognized as a comorbidity in women with PCOS, suggesting a possible interrelation between these conditions that warrants further investigation. Objective: This study aimed to explore the association between NAHSD and PCOS among women in the Swabi district of Khyber Pakhtunkhwa, Pakistan, with an emphasis on understanding the prevalence and sonographic characteristics of these conditions in the affected population. Methods: A cross-sectional study was conducted at the Department of Radiology, Mahaban Medical and Research Hospital, Swabi, KP, Pakistan. The study included 86 women with a history of irregular menstrual cycles or amenorrhea. Sonographic examinations were performed using a Toshiba prime ultrasound machine with convex (3.0—5.0 MHz) and linear (7.0—14.0 MHz) transducers. Clinical and sonographic data pertaining to PCOS and NAHSD were collected, including ovarian volume and liver echogenicity grading. Statistical analysis was conducted using SPSS version 25. Results: The mean age of participants was 27.5 ± 4.8 years. The mean ovarian volumes were 11.52 ml (right ovary) and 10.80 ml (left ovary). The prevalence of NAHSD in our study cohort was 46.5%. Furthermore, hirsutism was observed in 22.1% of the patients. A significant association between the presence of NAHSD and PCOS was identified, with higher rates of hepatic steatosis observed among the PCOS patients compared to those without PCOS. Conclusion: The findings from this study underscore a significant association between NAHSD and PCOS among women in the Swabi district, suggesting that women with PCOS are at an increased risk of developing fatty liver disease. This association highlights the need for comprehensive screening and management strategies to address these comorbid conditions effectively.

Development and Internal Validation of a Model for Predicting Overall Survival in Subjects with MAFLD: A Cohort Study.

Background & Aims: Fatty liver disease with metabolic dysfunction (MAFLD) is a new concept proposed to replace the previous concept of Non-Alcoholic Hepatic Steatosis (NAFLD). We developed and internally validated a prognostic model to predict the likelihood of death in a cohort of subjects with MAFLD. Methods: Our work involved two steps: the first was the construction of a bootstrapped multivariable Cox model for mortality risk prognosis and the second was its validation. Results: The study cohort included 1506 subjects, of which 907 were used for internal validation. Discriminant measures for the final model were R2D 0.6845 and Harrell's C 0.8422 in the development and R2D 0.6930 and Harrell's C 0.8465 in the validation. We used the nine independent prognostic factors selected by the LASSO Cox procedure and fitted by the bootstrap Cox survival model, and observed β were: Gender 0.356 1.42 (p < 0.008), Age 0.146 (p < 0.001), Glycemia 0.004 (p < 0.002), Total Cholesterol -0.0040 (p < 0.009), Gamma Glutamyl Transpeptidase 0.009 (p < 0.001), SBP 0.009 (p < 0.036), DBP -0.016 (p < 0.041), ALP 0.008 (p < 0.071) and Widowhood 0.550 (p < 0.001). Conclusions: We produced and validated a model to estimate the probability of death in subjects with MAFLD. The instruments we used showed satisfactory predictive capabilities.

Pancreatic steatosis is an independent risk factor for post-transplant diabetes mellitus in kidney transplant patients.

Post-transplant diabetes mellitus (PTDM) is associated with an increased risk of post-transplant cardiovascular diseases, and several risk factors of PTDM have been shown in the literature. Yet, the relationship between hepatic and pancreatic steatosis with post-transplant diabetes mellitus remains vague. We aimed to evaluate pancreatic steatosis, a novel component of metabolic syndrome, and hepatic steatosis association with post-transplant diabetes mellitus in a single-center retrospective cohort study conducted on kidney transplant recipients. We have performed a single-center retrospective cohort study involving all kidney transplant recipients. We have utilized pretransplant Fibrosis-4, nonalcoholic fatty liver disease fibrosis score, and abdominal computed tomography for the assessment of visceral steatosis status. We have included 373 kidney transplant recipients with a mean follow-up period of 32 months in our final analysis. Post-transplant diabetes mellitus risk is associated with older age (p<.001), higher body-mass index (p<.001), nonalcoholic fatty liver disease-fibrosis score (p=.002), hepatic (p<.001) or pancreatic (p<.001) steatosis on imaging and higher pre-transplant serum triglyceride (p=.003) and glucose levels (p=.001) after multivariate analysis. Our study illustrates that recipients' pancreatic steatosis is an independent predictive factor for post-transplant diabetes mellitus including in kidney transplant patients.

Non-alcoholic hepatic steatosis and its relation with metabolic syndrome

Objective: The aim of this study is to investigate the relationship between Non-Alcoholic Hepatic Steatosis (NASH) and Metabolic Syndrome (MS). Bibliographic review: NASH is a common liver condition in western industrialized countries, affecting individuals who do not consume alcohol. The pathogenesis of NASH involves environmental, genetic, and gut microbiota factors, and there is a strong association between NASH and MS, a condition that increases the risk of cardiovascular disease and type 2 diabetes. The relationship between NASH and MS is complex, with both sharing features such as obesity, insulin resistance and inflammation. The study analyzed 13 articles and found a strong association between NASH and MS. Patients with NASH often have features of MS, including type 2 diabetes, obesity, and hypertension. Furthermore, the presence of MS is related to a higher risk of liver disease progression. The relationship between these conditions appears to be driven by factors such as elevated glucose, insulin resistance and increased visceral fat. Final considerations: NASH and MS are conditions that pose significant public health challenges, especially in developed countries. The prevention and control of these conditions are closely linked to the promotion of lifestyle changes, including a healthy diet and physical exercise. These changes can have a positive impact on the incidence and progression of both NASH and MS, improving quality of life and reducing the risks associated with these pathological conditions. In addition, the importance of considering genetics and other individual factors in the evaluation and management of these multifactorial conditions is highlighted.

ROLE OF PHYSICAL ACTIVITY IN THE PREVENTION AND MANAGEMENT OF NON-ALCOHOLIC FATTY LIVER DISEASE

Non-alcoholic Hepatic Steatosis (NAFLD) is a major global cause of chronic liver disease. Its prevalence increases with the rise in metabolic syndrome components, primarily obesity and insulin resistance. The etiology of NAFLD is multifactorial, and recent studies suggest a "multiple hit" hypothesis that includes a combination of genetic, metabolic, and environmental factors. Lifestyle habits, including physical activity, play a significant role in its management. This study investigated the relationship between physical activity levels and the prevalence and severity of NAFLD in adults. A cross-sectional approach was used with a total of 250 participants. The participants were evenly divided into two groups: those diagnosed with NAFLD (n=125) and control subjects without NAFLD (n=125). Stratification was carefully executed to ensure equivalence in age, gender, and main co-morbidities to eliminate potential confounding variables. Among the 250 participants, with 125 individuals each in the NAFLD and control groups, no significant differences in age, BMI, or prevalence of co-morbidities such as diabetes and hypertension were observed. However, hepatic biochemical markers exhibited substantial differences between groups. ALT levels averaged 67.3 23.7 U/L for NAFLD participants compared to 24.2 ± 10.8 U/L in controls (p &lt; 0.001); AST levels were at 54.8 ± 19.6 U/L for NAFLD versus 23.4 ± 8.9 U/L for controls (p &lt; 0.001); GGT showed 89.2 ± 32.5 U/L in NAFLD individuals contrasting with 29.5 ± 13.4 U/L in controls (p &lt; 0.001). Furthermore, the FIB-4 index was higher in the NAFLD cohort (2.4 ± 0.6) than in controls (1.3 ± 0.4; p &lt; 0.001), and serum Albumin levels in NAFLD participants were 3.8 ± 0.5 g/dL, notably lower than the control's 4.5 ± 0.3 g/dL (p &lt; 0.001). The study concludes that physical activity is inversely associated with the prevalence and severity of NAFLD. Regular physical activity may be a key strategy in preventing and managing NAFLD.

The macrophage STING-YAP axis controls hepatic steatosis by promoting the autophagic degradation of lipid droplets.

The hallmark of NAFLD or hepatic steatosis is characterized by lipid droplet (LD) accumulation in hepatocytes. Autophagy may have profound effects on lipid metabolism and innate immune response. However, how innate immune activation may regulate the autophagic degradation of intracellular LDs remains elusive. A mouse model of a high-fat diet-induced NASH was used in the myeloid-specific stimulator of interferon genes (STING) knockout or STING/yes-associated protein (YAP) double knockout mice. Liver injury, lipid accumulation, lipid droplet proteins, autophagic genes, chromatin immunoprecipitation coupled with massively parallel sequencing, and RNA-Seq were assessed in vivo and in vitro . We found that high-fat diet-induced oxidative stress activates STING and YAP pathways in hepatic macrophages. The acrophage STING deficiency (myeloid-specific STING knockout) enhances nuclear YAP activity, reduces lipid accumulation, and increases autophagy-related proteins ATG5, ATG7, and light chain 3B but diminishes LD protein perilipin 2 expression. However, disruption of STING and YAP (myeloid STING and YAP double knockout) increases serum alanine aminotransferase and triglyceride levels and reduces β-fatty acid oxidation gene expression but augments perilipin 2 levels, exacerbating high-fat diet-induced lipid deposition. Chromatin immunoprecipitation coupled with massively parallel sequencing reveals that macrophage YAP targets transmembrane protein 205 and activates AMP-activated protein kinase α, which interacts with hepatocyte mitofusin 2 and induces protein disulfide isomerase activation. Protein disulfide isomerase activates hypoxia-inducible factor-1α signaling, increases autophagosome colocalization with LDs, and promotes the degradation of perilipin 2 by interacting with chaperone-mediated autophagy chaperone HSC70. The macrophage STING-YAP axis controls hepatic steatosis by reprogramming lipid metabolism in a transmembrane protein 205/mitofusin 2/protein disulfide isomerase-dependent pathway. These findings highlight the regulatory mechanism of the macrophage STING-driven YAP activity on lipid control.

Prognostic value of coronary artery calcium score for the prediction of atherosclerotic cardiovascular disease in participants with suspected nonalcoholic hepatic steatosis: Results from the multi-ethnic study of atherosclerosis

Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) events; thus, a diagnostic approach to help identify NAFLD patients at high risk is needed. In this study, we hypothesized that coronary artery calcium (CAC) screening could help stratify the risk of ASCVD events in participants with suspected nonalcoholic hepatic steatosis. A total of 713 participants with suspected nonalcoholic hepatic steatosis without previous cardiovascular events from the Multi-Ethnic Study of Atherosclerosis (MESA) were followed for the occurrence of incident ASCVD. Nonalcoholic hepatic steatosis was defined using nonenhanced computed tomography and liver/spleen attenuation ratio <1. Cox proportional hazards regression models were used to estimate hazard ratios (HR). C-statistics and areas under the time-dependent receiver operating characteristic curves (tAUC) were used to compare incremental contributions of CAC score when added to the clinical risk factors. In multivariable analyses, CAC score was found to be independently associated with incident ASCVD (HR=1.33, 95% CI=1.22-1.44, P < .001). The addition of CAC score to clinical risk factors increased the C-statistic from 0.677 to 0.739 (P < .001) and tAUC at 10 years from 0.668 to 0.771, respectively. In subgroup analyses, the incremental prognostic value of CAC score was more significant in participants with low/borderline- (<7.5%) and intermediate- (7.5%-20%) 10-year ASCVD risk scores. The inclusion of CAC score in global risk assessment was found to significantly improve the classification of incident ASCVD events in participants with suspected nonalcoholic hepatic steatosis, indicating a potential role for CAC screening in risk assessment.

Derlin-1 ameliorates nonalcoholic hepatic steatosis by promoting ubiquitylation and degradation of FABP1

Background and aimsThe functions of liver fatty acid binding protein 1 (FABP1) in the regulation of nonalcoholic fatty liver disease (NAFLD) have been previously established. However, how FABP1 expression is dynamically regulated in metabolic disorders is unclear. Previous studies have reported that ubiquitin proteasome-mediated degradation of FABP1 is involved, but the mechanism remains unknown. MethodsDysregulated expression of hepatic FABP1 and Derlin-1 was observed in NAFLD patients. We performed mice hepatic tissue coimmunoprecipitation based mass spectrum assays. Interaction between Derlin-1 and FABP1, and its impact on FABP1 ubiquitination status was evaluated by coimmunoprecipitation. The role of Derlin-1 in lipid deposition was tested using adenovirus-mediated overexpression in C57BL/6 mice, as well as by Derlin-1 overexpression or knockdown in HepG2 cells. ResultsAs a subunit of the endoplasmic reticulum-associated degradation complex, Derlin-1 was negatively associated with NAFLD patients, interacted with and ubiquitinated FABP1. Derlin-1 suppressed FABP1 levels and inhibited lipid deposition through a FABP1-dependent pathway. Additionally, Trim25, an E3 ubiquitin ligase present in the endoplasmic reticulum, was recruited to promote Derlin-1-related polyubiquitylation of FABP1, thereby creating a ubiquitin-associated network for FABP1 regulation. Derlin-1 overexpression ameliorated hepatic steatosis in both C57BL/6 mice and HepG2 cells, and contributed to attenuated weight gain, lower liver weight, and visceral fat mass. ConclusionsFABP1 was degraded by Derlin-1 through ubiquitin modification. Negative regulation of FABP1 by Derlin-1 overexpression, suppressed lipid metabolism and alleviated lipid deposition in vivo and in vitro. Hence, Derlin-1 activation in hepatocytes may represent a potential therapeutic strategy for NAFLD.

Role of purinergic signalling in obesity-associated end-organ damage: focus on the effects of natural plant extracts.

Obesity has become one of the major public health problems in both the developing and developed countries. Recent studies have suggested that the purinergic signalling is involved in obesity-associated end-organ damage through purine P1 and P2 receptors. In the search for new components for the treatments of obesity, we and other researchers have found much evidence that natural plant extracts may be promising novel therapeutic approaches by modulating purinergic signalling. In this review, we summarize a critical role of purinergic signalling in modulating obesity-associated end-organ damage, such as overhigh appetite, myocardial ischemia, inflammation, atherosclerosis, non-alcoholic fatty liver disease (NAFLD), hepatic steatosis and renal inflammation. Moreover, we focus on the potential roles of several natural plant extracts, including quercetin, resveratrol/trans-resveratrol, caffeine, evodiamine and puerarin, in alleviating obesity-associated end-organ damage via purinergic signalling. We hope that the current knowledge of the potential roles of natural plant extracts in regulating purinergic signalling would provide new ideas for the treatment of obesity and obesity-associated end-organ damage.

LIPOPROTEIN(A) IN CVR EVALUATION

Objective: High values of lipoprotein(a), related to atherosclerosis progression, are often considered a marker of thrombosis. We assessed the lipoprotein(a) profile in a group of patients with high vascular risk and no cardiovascular events, established its correlation with other cardiovascular risk factors (CVRF) and inferred the results for patients with metabolic disorders and, at least, two risk factors. Design and method: This longitudinal observational study included 516 patients, who had at least two cardiovascular risk factors and regularly attended, for at least two years, the outpatient consultations at a clinic of metabolism and vascular risk for primary prevention. Sociodemographic, clinical and anthropometric parameters were obtained at the baseline visit. Hepatic morphology was assessed in 509 patients (98.6%) by ultrasonography. The 10-year vascular risk was estimated using Framingham risk score (FRS), atherosclerotic cardiovascular disease (ASCVD) and systematic coronary risk evaluation (SCORE) tables. Results: Significant correlations were found between lipoprotein(a) levels and the addressed vascular risk factors, as well as between lipoprotein(a), and FRS, ASCVD and SCORE evaluation charts. Lipoprotein(a) values were also considerably higher in patients with steatosis. Increased lipoprotein(a) values were directly associated with all markers of cardiovascular risk and with non-alcoholic hepatic steatosis. Conclusions: Due to its high availability and low cost, lipoprotein(a) should become part of the routine evaluation of patients at vascular and should be decisive part in the calculation of vascular risk regardeless of age group.

Diosgenin attenuates nonalcoholic hepatic steatosis through the hepatic FXR-SHP-SREBP1C/PPARα/CD36 pathway

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and has no approved treatment. The hepatic farnesoid X receptor (FXR) is one of the most promising therapeutic targets for NAFLD. Diosgenin (DG), a natural compound extracted from Chinese herbal medicine, is very effective in preventing metabolic diseases. Our research aims to determine the effects and molecular mechanisms of DG on NAFLD in vivo and in vitro. The effect of DG on hepatic steatosis was evaluated in Sprague‒Dawley (SD) rats induced by a high-fat diet (HFD) and in HepG2 cells exposed to free fatty acids (FFAs, sodium oleate:sodium palmitate = 2:1). DG treatment efficiently managed hepatic lipid deposition in vivo and in vitro. Mechanistically, DG upregulated the expression of FXR and small heterodimer partner (SHP) and downregulated the expression of genes involved in hepatic de novo lipogenesis (DNL), including sterol regulatory element-binding protein 1C (SREBP1C), acetyl-CoA carboxylase 1 (ACC1), and fatty acid synthase (FASN). Moreover, DG promoted the expression of peroxisome proliferator-activated receptor alpha (PPARα), which is related to fatty acid oxidation. In addition, DG inhibited the expression of the CD36 molecule (CD36) related to fatty acid uptake. However, hepatic FXR silencing weakened the regulatory effects of DG on these genes. Collectively, our data show that DG has a good effect on alleviating nonalcoholic hepatic steatosis via the hepatic FXR-SHP-SREBP1C/PPARα/CD36 pathway. DG promises to be a novel candidate FXR activator that can be utilized to treat NAFLD.

The experience of the "Nicolae Malaxa" Clinical Hospital Bucharest, 2021-2022: non-alcoholic hepatic steatosis – etiological and risk profile

The experience of the "Nicolae Malaxa" Clinical Hospital Bucharest, 2021-2022: non-alcoholic hepatic steatosis – etiological and risk profile

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.

Low levels of osteocalcin, but not CTX or P1NP, are associated with nonalcoholic hepatic steatosis and steatohepatitis

AimThe association of bone turnover with the incidence and progression of nonalcoholic fatty liver disease (NAFLD) is unclear. We aimed to evaluate serum levels of bone turnover markers in relation to NAFLD and nonalcoholic hepatic steatohepatitis (NASH). MethodsTwo cohorts were involved in our study. For the first cohort, 370 participants without NAFLD were retrospectively recruited and followed up for incident NAFLD according to ultrasound. For the second cohort, 562 subjects who underwent liver biopsy were included and grouped into non-NAFLD, non-NASH or NASH according to the NASH Clinical Research Network system. The bone turnover markers osteocalcin, C-terminal telopeptide (CTX) and N-terminal propeptide of type-1 procollagen (P1NP) were measured. ResultsBaseline osteocalcin was significantly lower in subjects who developed NAFLD (13.93 [11.03;16.39] versus 18.24 [15.45;22.47] ng/ml, P < 0.001), with a median of 26.4 months of follow-up. Low levels of osteocalcin, but not CTX or P1NP, was an independent predictor of incident NAFLD (OR 0.755 [95%CI 0.668; 0.855] P < 0.001). Moreover, the osteocalcin level was negatively associated with the degree of liver steatosis. Furthermore, subjects with NASH had significantly lower osteocalcin than non-NASH and non-NAFLD group (13.28 [10.49;16.59] versus 14.91 [12.45;18.09] versus 18.21 [15.04;22.05] ng/ml, all P < 0.001). A low osteocalcin level was an independent risk factor for NASH (OR for highest versus lowest quartile: 0.282 [0.147;0.543] P < 0.001). ConclusionLow level of osteocalcin, but not CTX or P1NP, was associated with NAFLD and NASH, indicating its potential role as an important endocrine regulator of hepatic energy metabolism.

Association of severity of coronary and carotid atherosclerosis and functional condition of a liver at patients with stable stenocardia and obesity

The aim. To assess the relationships between the degree of severity of coronary and carotid atherosclerosis and the functional liver condition in patients with stable angina pectoris and obesity. Research materials and methods. During the study, two groups of patients were formed. Group I was composed of patients with stable angina and obesity (n = 69), group II - patients with stable angina with a normal body mass index (BMI) (n = 35). Measures of liver function, carbohydrate and lipid metabolism, results of duplex scanning of extracranial brachiocephalic arteries (BCA DS), coronaroangiography (CAG) data were evaluated, and biomarker of hepatic steatosis (НSI) were calculated. The severity of coronary atherosclerosis was analyzed by Gensini score (GS). All patients underwent ultrasound of the liver (ultrasound). Results. In 100% of patients of group I, non-alcoholic hepatic steatosis was detected according to ultrasound. Biomarker of hepatic steatosis (HSI) proved to be more significant among group I patients, while confirming the presence of steatosis. In patients of group I, more significant hypertriglyceridemia was established. Atherosclerotic plaques (according to the BCA DS) were detected in 100% patients of group I and in 68,5% patients of group II. Pronounced stenosis of СCA (≥75% of vessel lumen) is established in 14,5% patients of group I, and is not found among patients of group II. The proportion of patients with significant СA stenosis (&gt; 70% vessel lumen) turned out to be greater in the I group, making up 69,5%, in the II group - 42,8% (χ2=6,9; р=0,009). The GS index values were more significant in patients of group I compared to group II (p = 0.01). Close correlation relationships have been identified between functional liver condition and the severity of coronary and carotid atherosclerosis. Biomarker of steatosis (HSI) have demonstrated their relationship with atherosclerotic lesions of ССA and CA. Conclusion. Against the background of impaired the functional liver condition in patients with stable stenocardia and obesity, more significant expression of coronary and carotid atherosclerosis is determined in comparison with patients with normal body mass index.

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.

Prognostic Capabilities of Diagnosing Non-Alcoholic Hepatic Steatosis at Early Stages of Its Development.

Patients with excessive body mass (n=26) and obesity (n=28) having different concomitant pathologies of the digestive organs have undergone a comprehensive examination including assessment of biochemical blood indices, ultrasound examination of the abdominal organs, dynamic hepatobiliscintigraphy, assessment of the comorbidity level as a whole (calculation of CIRS) and by the available pathology of the digestive organs. The ultrasound signs of hepatic steatosis have been found in all patients with obesity stage II and III, in 69.2% of the examined patients (95% CI: 42.37-87.32) with obesity stage I, in 30.8% (95% CI: 16.50-49.99) with excessive body mass, and in 13.9% of patients (95% CI: 6.08-28.66) with normal body mass. According to the ROC analysis, the predictors of hepatic steatosis development in patients with excessive body mass and obesity are BMI (>31, р<0.0001) and the number of digestive organ illnesses (more than 4 diseases, p<0.0001). On the basis of the data obtained, a logistic model has been developed in the form of the regression equation permitting us to predict the groups of patients with a low or high degree of risk of hepatic steatosis. The analysis of dynamic hepatobiliscintigraphy has revealed deceleration of the absorbing function of hepatocytes in patients with normal ultrasound images of the liver even in case of excessive body mass. The obtained results made it possible to develop a method of diagnosing fatty hepatosis with subsequent calculation of the functional hepatocyte activity index (FHAI) which helps not only establish functional disorders but identify the group of patients having the risk of developing these disorders. Normal ultrasound imaging of the liver and absence of the biochemical changes in the blood are not indicators of preservation of its functional activity, since the risk of functional disorders was found in 32.3% of cases (95% CI: 18.57-49.86) and reversible disorders in 19.3% (95% CI: 9.19-36.28) when FHAI was calculated for patients with normal body mass. With the increase of body mass, irreversible functional disorders of hepatocytes are observed in 80-100% of patients.Thus, the results obtained in the course of the investigation have confirmed the possibility of using new prognostic markers of hepatic steatosis for early diagnosis of non-alcoholic fatty liver disease.

L-theanine prevents progression of nonalcoholic hepatic steatosis by regulating hepatocyte lipid metabolic pathways via the CaMKK\u03b2-AMPK signaling pathway

BackgroundL-theanine, a non-protein amino acid was found principally in the green tea, has been previously shown to exhibit potent anti-obesity property and hepatoprotective effect. Herein, we investigated the effects of L-theanine on alleviating nonalcoholic hepatic steatosis in vitro and in vivo, and explored the underlying molecular mechanism.MethodsIn vitro, HepG2 and AML12 cells were treated with 500 μM oleic acid (OA) or treated with OA accompanied by L-theanine. In vivo, C57BL/6J mice were fed with normal control diet (NCD), high‐fat diet (HFD), or HFD along with L-theanine for 16 weeks. The levels of triglycerides (TG), accumulation of lipid droplets and the expression of genes related to hepatocyte lipid metabolic pathways were detected in vitro and in vivo.ResultsOur data indicated that, in vivo, L-theanine significantly reduced body weight, hepatic steatosis, serum levels of alanine transaminase (ALT), aspartate transaminase (AST), TG and LDL cholesterol (LDL-C) in HFD-induced nonalcoholic fatty liver disease (NAFLD) mice. In vitro, L-theanine also significantly alleviated OA induced hepatocytes steatosis. Mechanic studies showed that L-theanine significantly inhibited the nucleus translocation of sterol regulatory element binding protein 1c (SREBP-1c) through AMPK-mTOR signaling pathway, thereby contributing to the reduction of fatty acid synthesis. We also identified that L-theanine enhanced fatty acid β-oxidation by increasing the expression of peroxisome proliferator–activated receptor α (PPARα) and carnitine palmitoyltransferase-1 A (CPT1A) through AMP-activated protein kinase (AMPK). Furthermore, our study indicated that L-theanine can active AMPK through its upstream kinase Calmodulin-dependent protein kinase kinase-β (CaMKKβ).ConclusionsTaken together, our findings suggested that L-theanine alleviates nonalcoholic hepatic steatosis by regulating hepatocyte lipid metabolic pathways via the CaMKKβ-AMPK signaling pathway.