Adherence to Mediterranean Diet and NAFLD in Patients with Metabolic Syndrome: The FLIPAN Study.

Unhealthy diet is an important factor in the progression of non-alcoholic fatty liver disease (NAFLD). Previous studies showed the benefits of a Mediterranean diet (MedDiet) on Metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM), and cardiovascular diseases, which usually have a pathophysiological relationship with NAFLD. To assess the effect of adherence to a MedDiet on NAFLD in MetS patients after lifestyle intervention, this multicentre (Mallorca and Navarra, Spain) prospective randomized trial, with personalized nutritional intervention based on a customized MedDiet, coupled with physical activity promotion was performed to prevent, and reverse NAFLD among patients with MetS. The current analysis included 138 patients aged 40 to 60 years old, Body Mass Index (BMI) 27-40 kg/m2, diagnosed with NAFLD using MRI, and MetS according to the International Diabetes Federation (IDF). A validated food frequency questionnaire was used to assess dietary intake. Adherence to Mediterranean diet by means of a 17-item validated questionnaire, anthropometrics, physical activity, blood pressure, blood biochemical parameters, and intrahepatic fat contents (IFC) were measured. The independent variable used was changes in MedDiet adherence, categorized in tertiles after 6 months follow-up. Subjects with high adherence to the MedDiet showed higher decreases in BMI, body weight, WC, SBP, DBP, and IFC. An association between improvement in adherence to the MedDiet and amelioration of IFC after 6-month follow-up was observed. High adherence to the MedDiet is associated with better status of MetS features, and better values of IFC.

Bisphenol-A exposure worsens hepatic steatosis in ovariectomized mice fed on a high-fat diet: Role of endoplasmic reticulum stress and fibrogenic pathways.

AIMS: Bisphenol (BP)-A exposure can impair glucose and lipid metabolism. However, it is unclear whether this endocrine disruptor (ED) modulates these processes in postmenopause, a period with organic changes that increase the risk for metabolic diseases. Herein, we evaluated the effects of BPA exposure on adiposity, glucose homeostasis and hepatic steatosis in ovariectomized (OVX) mice fed on a high-fat diet (HFD). MAIN METHODS: Adult Swiss female mice were OVX and submitted to a normolipidic diet or HFD and drinking water without [control (OVX CTL) and OVX HFD groups, respectively] or with 1 µg/mL BPA (OVX CBPA and OVX HBPA groups, respectively), for 3 months. KEY FINDINGS: OVX HFD females displayed increased adiposity, glucose intolerance, insulin resistance and moderate hepatic steatosis. This effect was associated with a high hepatic expression of genes involved in lipogenesis (Srebf1 and Scd1), ß-oxidation (Cpt1a) and endoplasmic reticulum (ER) stress (Hspa5 and Hyou1). BPA did not alter adiposity or glucose homeostasis disruptions induced by HFD. However, this ED triggered severe steatosis, exacerbating hepatic fat and collagen depositions in OVX HBPA, in association with a reduction in Mttp mRNA, and up-regulation of genes involved in ß-oxidation (Acox1 and Acadvl), mitochondrial uncoupling (Ucp2), ER stress (Hyou1 and Atf6) and chronic liver injury (Tgfb1and Casp8). Furthermore, BPA caused mild steatosis in OVX CBPA females, increasing the hepatic total lipids and mRNAs for Srebf1, Scd1, Hspa5, Hyou1 and Atf6. SIGNIFICANCE: BPA aggravated hepatic steatosis in OVX mice. Especially when combined with a HFD, BPA caused NAFLD progression, which was partly mediated by chronic ER stress and the TGF-ß1 pathway.

Accuracy of common proton density fat fraction thresholds for magnitude- and complex-based chemical shift-encoded MRI for assessing hepatic steatosis in patients with obesity.

PURPOSE: MRI proton density fat fraction (PDFF) can be calculated using magnitude (MRI-M) or complex (MRI-C) MRI data. The purpose of this study was to identify, assess, and compare the accuracy of common PDFF thresholds for MRI-M and MRI-C for assessing hepatic steatosis in patients with obesity, using histology as reference. METHODS: This two-center prospective study included patients undergoing MRI-C- and MRI-M-PDFF estimations within 3 days before weight loss surgery. Liver biopsy was performed, and histology-determined steatosis grades were used as reference standard. Using receiver operating characteristics (ROC) analysis on data pooled from both methods, single common thresholds for diagnosing and differentiating none or mild (0-1) from moderate to severe steatosis (2-3) were selected as the ones achieving the highest sensitivity while providing at least 90% specificity. Selection methods were cross-validated. Performances were compared using McNemar's tests. RESULTS: Of 81 included patients, 54 (67%) had steatosis. The common PDFF threshold for diagnosing steatosis was 5.4%, which provided a cross-validated 0.88 (95% CI 0.77-0.95) sensitivity and 0.92 (0.75-0.99) specificity for MRI-M and 0.87 sensitivity (0.75-0.94) with 0.81 (0.61-0.93) specificity for MRI-C. The common PDFF threshold to differentiate steatosis grades 0-1 from 2 to 3 was 14.7%, which provided cross-validated 0.86 (95% CI 0.59-0.98) sensitivity and 0.95 (0.87-0.99) specificity for MRI-M and 0.93 sensitivity (0.68-0.99) with 0.97(0.89-0.99) specificity for MRI-C. CONCLUSION: If independently validated, diagnostic thresholds of 5.4% and 14.7% could be adopted for both techniques for detecting and differentiating none to mild from moderate to severe steatosis, respectively, with high diagnostic accuracy.

Regulation of glucose and lipid metabolism by the pancreatic and extra-pancreatic actions of taurine.

The beneficial actions of L-taurine (Tau) against glucose intolerance, obesity, type 2 diabetes (T2D), and non-alcoholic fat liver disease (NAFLD) have been linked to its antioxidant and anti-inflammatory effects, which ameliorate tissue insulin sensitivity. Importantly, there are several lines of evidence that indicate a direct action of Tau on the endocrine pancreas to regulate the secretion and paracrine actions of insulin, glucagon, and somatostatin. Furthermore, Tau can also ameliorate glucose metabolism through the enhancement of insulin signaling. However, some of the benefits of Tau upon intermediary metabolism may manifest via considerable antagonism of the action of insulin. Therefore, this review discusses the mechanisms of action by which Tau may regulate endocrine pancreatic morphofunction, and glucose and lipid homeostasis.

Interactions of central obesity with rs3918242 on risk of non-alcoholic fat liver disease: a preliminary case-control study.

NAFLD is a complex disease characterized by inflammation and insulin resistance which is determined by an interaction of genetics and environmental factors. MMP gene has been implicated in relation to inflammation and insulin resistance. The preliminary case-control study aimed to investigate the association between Matrix metalloproteinase (MMP)-9-1562C/T (rs3918242), MMP-2-1306C/T (rs243865) and risk of NAFLD and to further evaluate the interactions of central obesity with rs3918242 and rs243865. Two variants, rs3918242 and rs243865, were genotyped by polymerase chain reaction -restriction fragment length polymorphism. Gene-environment interactions on risk of NAFLD was preliminarily investigated by generalized multifactor dimensionality reduction (GMDR) and further confirmed by unconditional logistic regression methods. After adjusting for covariates, increased risk of NAFLD were observed in subjects carrying TT/CT genotypes in rs3918242 ((Adjust)OR=1.64, 95% CI: 1.24, 2.11, P=0.006). However, decreased risk of non-alcoholic fat liver disease was found when MMP-2 rs243865 (TT/CT) genotype carriers compared with CC carrier ((Adjust)OR=0.65, 95% CI: 0.47, 0.72, P=0.000).Interactions of central obesity with rs3918242 was preliminarily found by GMDR, with a maximum prediction accuracy (67.61%) and a maximum Cross-validation Consistency (10/10).The unconditional logistic regression method indicated central obesity-positive subject with genotype TT/CT had 4.54 times risk of NAFLD compared to central obesity-negative subjects with genotype CC (OR(add)(a)=4.54, 95% CI: 2.81, 7.21, P(add)(a)=0.000), which further confirmed the interactions. The results indicate that both rs3918242 and rs243865 is associated with risk of NAFLD. Furthermore, rs3918242 and central obesity have synergistic effects on risk of NAFLD.

Prevalencia de esteatosis hepática no alcohólica en autopsias y alteraciones morfológicas metabólicas relacionadas / Non-alcoholic hepatic steatosis prevalence in necropsies and related metabolic morphologic alterations

INTRODUCCIÓN: la enfermedad hepática por depósito de grasa no alcohólica se corresponde con alteraciones morfológicas hepáticas que excluyen el consumo de alcohol. OBJETIVO: identificar la prevalencia de la esteatosis hepática en el estudio de las autopsias. MÉTODOS: se revisaron las autopsias de los fallecidos adultos entre 1991-2009, en el Hospital Militar Central Dr. Luis Díaz Soto. Se excluyeron los fallecidos con historia conocida de ser alcohólicos y los portadores de hepatopatías virales (agudas y crónicas). Los casos se agruparon según la intensidad de la lesión grasa acumulada en los hepatocitos. Se analizaron las variables: grupos de edades, enfermedades metabólicas relacionadas y causa básica de muerte. Se revisaron 669 historias clínicas para evaluar el índice de masa corporal y relacionarlo con los resultados. RESULTADOS: todos los grupos de edades mostraron afectaciones por esteatosis, con mayor frecuencia entre los 55 y 84 años. En los 3 317 fallecidos con enfermedad hepática por depósito de grasa no alcohólica, se observó esteatosis hepática simple en 1 761 pacientes, esteatohepatitis en 1 468 casos y esteatosis hepática con fibrosis o cirrosis en 88 casos. En casi el 50 por ciento de los casos la esteatosis fue de intensidad moderada. Un 34,3 por ciento presentó infiltración grasa estromal páncreas/miocardio. Solo el 7,5 por ciento de los casos estudiados no tuvo lesión aterosclerótica. El 59,2 por ciento de los casos con esteatosis simple mostró un índice de masa corporal por encima de 30. La principal causa básica de muerte resultó ser la aterosclerosis coronaria (24,5 por ciento). CONCLUSIONES: las enfermedades relacionadas con el síndrome metabólico muestran sus alteraciones morfológicas en las autopsias con elevada frecuencia. La esteatosis hepática, en particular la enfermedad hepática por depósito de grasa no alcohólica, es un trastorno que presenta elevada prevalencia entre las alteraciones encontradas en las autopsias estudiadas(AU)

INTRODUCTION: the liver disease due to non-alcoholic fat depot corresponds to hepatic morphologic alterations excluding the alcohol consumption. OBJECTIVE: to identify the hepatic steatosis prevalence in the autopsies study. METHODS: the medical records from adult deceased from 1991 to 2009 in the Dr. Luis Díaz Soto Central Military Hospital were reviewed. The alcoholics and the carriers of viral liver diseases (acute and chronic) were excluded. Cases were grouped according to following variables: age groups, related metabolic diseases and the major cause of death. A total of 669 medical records were reviewed to assess the body mass index to relate it to results. RESULTS: all age groups showed affections due to steatosis more frequent between 55 and 84 years. In the 3 317 deceased with non-alcoholic fat-depot liver disease, it was noted the presence of simple liver steatosis, steatohepatitis in 1 468 cases and hepatic steatosis with fibrosis or cirrhosis in 88 cases. In almost the 50 percent of cases the steatosis was moderate intensity. The 34.3 percent showed pancreas/myocardium stromal fat infiltration. Only the 7.5 percent of study cases had not a atherosclerotic lesion. The 59.2 percent of cases presenting with simple steatosis showed a body mass index over 30. The major basic cause of death was the coronary atherosclerosis (24.5 percent). CONCLUSIONS: the diseases related to metabolic syndrome show their morphologic alterations with a high frequency. The hepatic steatosis, particularly the liver disease due to non-alcoholic fat depot, is a disorder with a high prevalence among the alterations found in study autopsies(AU)

Prevalencia de esteatosis hepática no alcohólica en autopsias y alteraciones morfológicas metabólicas relacionadas / Non-alcoholic hepatic steatosis prevalence in necropsies and related metabolic morphologic alterations

INTRODUCCIÓN: la enfermedad hepática por depósito de grasa no alcohólica se corresponde con alteraciones morfológicas hepáticas que excluyen el consumo de alcohol. OBJETIVO: identificar la prevalencia de la esteatosis hepática en el estudio de las autopsias. MÉTODOS: se revisaron las autopsias de los fallecidos adultos entre 1991-2009, en el Hospital Militar Central Dr. Luis Díaz Soto. Se excluyeron los fallecidos con historia conocida de ser alcohólicos y los portadores de hepatopatías virales (agudas y crónicas). Los casos se agruparon según la intensidad de la lesión grasa acumulada en los hepatocitos. Se analizaron las variables: grupos de edades, enfermedades metabólicas relacionadas y causa básica de muerte. Se revisaron 669 historias clínicas para evaluar el índice de masa corporal y relacionarlo con los resultados. RESULTADOS: todos los grupos de edades mostraron afectaciones por esteatosis, con mayor frecuencia entre los 55 y 84 años. En los 3 317 fallecidos con enfermedad hepática por depósito de grasa no alcohólica, se observó esteatosis hepática simple en 1 761 pacientes, esteatohepatitis en 1 468 casos y esteatosis hepática con fibrosis o cirrosis en 88 casos. En casi el 50 por ciento de los casos la esteatosis fue de intensidad moderada. Un 34,3 por ciento presentó infiltración grasa estromal páncreas/miocardio. Solo el 7,5 por ciento de los casos estudiados no tuvo lesión aterosclerótica. El 59,2 por ciento de los casos con esteatosis simple mostró un índice de masa corporal por encima de 30. La principal causa básica de muerte resultó ser la aterosclerosis coronaria (24,5 por ciento). CONCLUSIONES: las enfermedades relacionadas con el síndrome metabólico muestran sus alteraciones morfológicas en las autopsias con elevada frecuencia. La esteatosis hepática, en particular la enfermedad hepática por depósito de grasa no alcohólica, es un trastorno que presenta elevada prevalencia entre las alteraciones encontradas en las autopsias estudiadas

INTRODUCTION: the liver disease due to non-alcoholic fat depot corresponds to hepatic morphologic alterations excluding the alcohol consumption. OBJECTIVE: to identify the hepatic steatosis prevalence in the autopsies study. METHODS: the medical records from adult deceased from 1991 to 2009 in the Dr. Luis Díaz Soto Central Military Hospital were reviewed. The alcoholics and the carriers of viral liver diseases (acute and chronic) were excluded. Cases were grouped according to following variables: age groups, related metabolic diseases and the major cause of death. A total of 669 medical records were reviewed to assess the body mass index to relate it to results. RESULTS: all age groups showed affections due to steatosis more frequent between 55 and 84 years. In the 3 317 deceased with non-alcoholic fat-depot liver disease, it was noted the presence of simple liver steatosis, steatohepatitis in 1 468 cases and hepatic steatosis with fibrosis or cirrhosis in 88 cases. In almost the 50 percent of cases the steatosis was moderate intensity. The 34.3 percent showed pancreas/myocardium stromal fat infiltration. Only the 7.5 percent of study cases had not a atherosclerotic lesion. The 59.2 percent of cases presenting with simple steatosis showed a body mass index over 30. The major basic cause of death was the coronary atherosclerosis (24.5 percent). CONCLUSIONS: the diseases related to metabolic syndrome show their morphologic alterations with a high frequency. The hepatic steatosis, particularly the liver disease due to non-alcoholic fat depot, is a disorder with a high prevalence among the alterations found in study autopsies