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Objectives: To examine the influence of non-alcoholic fatty liver disease (NAFLD) and hepatic fat content on bone mineral density (BMD), and to investigate whether the relationship between NAFLD and BMD is independent of lifestyle factors related to BMD. Methods: Hepatic fat content (magnetic resonance imaging), BMD, lean mass index, total and abdominal fat mass (dual-energy-X-ray absorptiometry), moderate to vigorous physical activity (MVPA) (accelerometry), and calcium and vitamin D intake (two 24 h recalls) were measured in 115 children with overweight/obesity aged 10.6 +/- 1.1 years old. Result: Children with NAFLD had lower BMD than children without NAFLD regardless of sex, puberty stage, lean mass index, fat mass, MVPA, and calcium and vitamin D intake (0.89 +/- 0.01 vs. 0.93 +/- 0.01 g/cm(2) for NAFLD and non-NAFLD, respectively, P < 0.01). Higher hepatic fat content was significantly associated with lower BMD regardless of confounders (adjusted P < 0.05). Conclusions: Findings of the current study suggest that hepatic fat accumulation is associated with decreased BMD independently of adiposity, and regardless of those lifestyle factors closely related to bone mineral accrual in children. These results may have implication in the clinical management of children with overweight/obesity given the high prevalence of pediatric NAFLD. ; The current project was supported by the Spanish Ministry of Industry and Competitiveness (DEP2016-78377-R), by "Fondos Estructurales de la Union Europea (FEDER), Una manera de hacer Europa", and by the University of the Basque Country (GIU14/21). This work was also supported by grants from Spanish Ministry of Economy and Competitiveness (RYC-2010-05957; RYC-2011-09011), Spanish Ministry of Education, Culture and Sports (FPU14/03329), and by the Education, Linguistic Policy and Culture Department of the Government of the Basque Country (PRE_2016_1_0057), and also by "Programa de Captacion de Talento - UGR Fellows" as part of "Plan Propio" of the University of Granada (Spain).

Pediatric non-alcoholic fatty liver disease (NAFLD) has increased in parallel with childhood obesity. Dietary habits, particularly products rich in sugars, may influence both hepatic fat and insulin resistance (HOMA-IR). The aim of the study was to examine the associations of the consumption of foods (cereals, fruits and vegetables, meat/meat products, dairy products, dairy desserts/substitutes (DDS) fish/shellfish, total and added sugars), sugar-sweetened beverages (SSB) and food components (macronutrients and fiber), on hepatic fat and HOMA-IR. Dietary intake (two non-consecutive 24h-recalls), hepatic fat (magnetic resonance imaging) and HOMA-IR were assessed in 110 children (10.6-1.1 years old) with overweight/obesity. Linear regression analyses were used to examine the associations of dietary intake with hepatic fat and HOMA-IR adjusted for potential confounders (sex, age, energy intake, maternal educational level, total and abdominal adiposity and sugar intake). The results showed that there was a negative association between cereal intake and hepatic fat (-0.197, P<0.05). In contrast, both SSB consumption (=0.217; P=0.028) and sugar in SSB (=0.210, P=0.035), but not DDS or sugar in DDS or other dietary components, were positively associated with hepatic fat regardless of potential confounders including total sugar intake. In conclusion, cereal intake might decrease hepatic fat, whereas SSB consumption and its sugar content may increase the likelihood of having hepatic steatosis. Although these observations need to be confirmed using experimental evidence, these results suggest that healthy lifestyle intervention programs are needed to improve dietary habits as well as to increase the awareness of the detrimental effects of SSB consumption early in life. ; This project was supported by the Spanish Ministry of Industry and Competitiveness (DEP2016-78377-R), by 'Fondos Estructurales de la Unión Europea (FEDER), Una manera de hacer Europa' and by the University of the Basque Country (GIU14/21). This work was also supported by grants from Spanish Ministry of Economy and Competitiveness (RYC 2010-05957; RYC-2011-09011), by the Education Department of the Government of the Basque Country (PRE_2016_1_0057, PRE_2017_2_0224 and PRE_2018_2_0057), by the Spanish Ministry of Education, Culture and Sports (FPU14/03329), and by the Swedish Society of Medicine.

AbstractAimsAlcohol-associated liver disease (ALD) is a global health problem caused, among other factors, by oxidative stress from the formation of reactive oxygen species (ROS). One important source of ROS is microsomal ethanol metabolism catalyzed by cytochrome P450 2E1 (CYP2E1), which is induced by chronic ethanol consumption. Inhibition of CYP2E1 by clomethiazole (CMZ) decreases oxidative stress in cell cultures and improves ALD in animal studies. Our study aimed to assess the benefits of a CYP2E1 inhibitor (clomethiazole) in detoxification of patients with ALD.MethodsOpen label, randomized controlled clinical trial to study whether CYP2E1 inhibition improves ALD in the patients with alcohol use disorders admitted for alcohol detoxification therapy (ADT). Patients had to have a serum aspartate aminotransferase (AST) activity exceeding twice the upper normal limit at time of admission and be non-cirrhotic defined by fibroscan value &lt;12 kPa. Sixty patients were randomly assigned to ADT with either CMZ or clorazepate (CZP) for 7–10 days in a 1:1 ratio. The chlorzoxazone test of CYP2E1 activity was performed at enrolment and at 2 points during the study.ResultsADT improved hepatic steatosis (controlled attenuation parameter) in both groups significantly. A trend towards a greater improvement in hepatic fat content during ADT (−21.5%) was observed in the CMZ group (252 ± 48 dB/m vs. 321 ± 38 dB/m; P &lt; 0.0001) compared with the CZP group (−13.9%; 273 ± 38 dB/m vs. 317 ± 39 dB/m; P &lt; 0.0001). As already reported, serum AST (P &lt; 0.004) and alanine aminotransferase (ALT) activities (P &lt; 0.0006) significantly decreased in CMZ patients as compared with patients on CZP by the end of hospitalization. A significant correlation was found between AST (P = 0.023), ALT (P = 0.009), GGT (P = 0.039) and CAP.ConclusionThis study demonstrates that CMZ improves clinical biomarkers for ALD in humans most likely due to its inhibitory effect on CYP2E1. Because of its addictive potential, CMZ can only be given for a short period of time and therefore other CYP2E1 inhibitors to treat ALD are needed.

This is an open-access article distributed under the terms of the Creative Commons Attribution License. ; The liver responds to estrogens and growth hormone (GH) which are critical regulators of body growth, gender-related hepatic functions, and intermediate metabolism. The effects of estrogens on liver can be direct, through the direct actions of hepatic ER, or indirect, which include the crosstalk with endocrine, metabolic, and sex-differentiated functions of GH. Most previous studies have been focused on the influence of estrogens on pituitary GH secretion, which has a great impact on hepatic transcriptional regulation. However, there is strong evidence that estrogens can influence the GH-regulated endocrine and metabolic functions in the human liver by acting at the level of GHR-STAT5 signaling pathway. This crosstalk is relevant because the widespread exposition of estrogen or estrogen-related compounds in human. Therefore, GH or estrogen signaling deficiency as well as the influence of estrogens on GH biology can cause a dramatic impact in liver physiology during mammalian development and in adulthood. In this review, we will summarize the current status of the influence of estrogen on GH actions in liver. A better understanding of estrogen-GH interplay in liver will lead to improved therapy of children with growth disorders and of adults with GH deficiency. © 2013 Fernández-Pérez, Guerra, Díaz-Chico and Flores-Morales. ; The research program in the author's lab is supported by grants-in-aid from the Spanish Ministry of Economy and Competitivity (MINECO) with the funding of European Regional Development Fund-European Social Fund (SAF2009-13296 and SAF2012-37344), Canary Islands Government (ACIISI PI2010), and Alfredo Martin-Reyes Foundation (Arehucas)-FICIC. ; Peer Reviewed

Sago starch which naturally contains high amount of resistant starch, comes to the attention due to its ability to confer health benefits as functional food i.e., prebiotic. The present work aimed to investigate the effects of sago starch consumption on body weight, satiation, caecum short chain fatty acids body, and hepatic lipid content on diet-induced obese rats for obesity management. A total of 36 male Sprague Dawley rats were fat-induced and divided into the obesity-prone and obesity-resistant groups. Eight percent and sixteen percent resistant starch from sago and Hi-maize260 were incorporated into the standardised feed formulation. Food intake was weighed throughout the intervention period. The caecum sample was subjected to short chain fatty acids analysis using HPLC. Hepatic lipid content was measured using the Folch method. Both dosages of sago starch (8 and 16% SRS) promoted body weight loss with a reduction of food intake, which suggested satiety. No significant differences was observed in the production of lactate, acetate, propionate, and butyrate from the caecum sample. Both dosages of sago starch (8 and 16% SRS) also showed lower hepatic lipid content and visceral adipose tissue than the baseline and control groups. However, 8% sago starch showed the lowest hepatic lipid content in obesity-prone and obesity-resistant groups. Overall results demonstrated that sago starch has the potential as an obesity and overweightness control regime as it promotes satiety, lowers visceral adipose tissue, and reduces hepatic lipid content. Consumers should consider adding sago starch in their daily meals.

Background: Naturally occurring variation in Membrane-bound O-acyltransferase domain-containing 7 (MBOAT7), encoding for an enzyme involved in phosphatidylinositol acyl-chain remodelling, has been associated with fatty liver and hepatic disorders. Here, we examined the relationship between hepatic Mboat7 down-regulation and fat accumulation. Methods: Hepatic MBOAT7 expression was surveyed in 119 obese individuals and in experimental models. MBOAT7 was acutely silenced by antisense oligonucleotides in C57Bl/6 mice, and by CRISPR/Cas9 in HepG2 hepatocytes. Findings: In obese individuals, hepatic MBOAT7 mRNA decreased from normal liver to steatohepatitis, independently of diabetes, inflammation and MBOAT7 genotype. Hepatic MBOAT7 levels were reduced in murine models of fatty liver, and by hyper-insulinemia. In wild-type mice, Mboat7 was down-regulated by refeeding and insulin, concomitantly with insulin signalling activation. Acute hepatic Mboat7 silencing promoted hepatic steatosis in vivo and enhanced expression of fatty acid transporter Fatp1. MBOAT7 deletion in hepatocytes reduced the incorporation of arachidonic acid into phosphatidylinositol, consistently with decreased enzymatic activity, determining the accumulation of saturated triglycerides, enhanced lipogenesis and FATP1 expression, while FATP1 deletion rescued the phenotype. Interpretation: MBOAT7 down-regulation by hyper-insulinemia contributes to hepatic fat accumulation, impairing phosphatidylinositol remodelling and up-regulating FATP1. Funding: LV was supported by MyFirst Grant AIRC n.16888, Ricerca Finalizzata Ministero della Salute RF-2016–02,364,358, Ricerca corrente Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico; LV and AG received funding from the European Union Programme Horizon 2020 (No. 777,377) for the project LITMUS-"Liver Investigation: Testing Marker Utility in Steatohepatitis". MM was supported by Fondazione Italiana per lo Studio del Fegato (AISF) 'Mario Coppo' fellowship.

OBJECTIVE Pediatric hepatic steatosis is highly prevalent and closely related to type 2 diabetes. This study aimed to determine whether the addition of supervised exercise to a family-based lifestyle and psycho-educational intervention results in greater reduction of percentage of hepatic fat (HF), adiposity, and cardiometabolic risk factors in children with overweight/obesity. RESEARCH DESIGN AND METHODS The study subjects of this nonrandomized, two-arm, parallel design clinical trial were 116 overweight/obese children (10.6 +/- 1.1 years of age, 53.4% girls) living in Vitoria-Gasteiz (Spain). For 22 weeks, they followed either a lifestyle and psycho-education program (control intervention [CInt], N = 57), consisting of two family-based education sessions/month, or the same plus supervised exercise (intensive intervention [II], N = 59) focused mainly on high-intensity aerobic workouts (3 sessions/week, 90 min/session). The primary outcome was the change in percentage of HF (as measured by MRI) between baseline and the end of the intervention period. Secondary outcomes included changes in BMI, fat mass index (FMI), abdominal fat (measured by DEXA), blood pressure, triglycerides, HDL, LDL, gamma-glutamyl transferase, glucose, and insulin concentrations. RESULTS A total of 102 children completed the trial (N = 53 and N = 49 in the CInt and II groups, respectively). Percentage of HF decreased only in the II group (-1.20 +/- 0.31% vs. 0.04 +/- 0.30%, II and CInt groups, respectively), regardless of baseline value and any change in adiposity (P < 0.01). BMI, FMI, abdominal fat (P <= 0.001), and insulin (P < 0.05) were reduced in both groups. CONCLUSIONS Multicomponent intervention programs that include exercise training may help to reduce adiposity, insulin resistance, and hepatic steatosis in overweight/obese children. ; This project was funded by the Spanish Ministry of Health 'Fondos de Investigation Sanitaria del Institute de Salud Carlos III' (PI13/01335), the Spanish Ministry of Industry and Competitiveness (DEP2016-78377-R), and by EU Fondos Estructurales de la Unión Europea (FEDER) funds ('Una manera de hacer Europa'). Support was also provided by grants from the Spanish Ministry of Education, Culture and Sports (FPU14/03329), the Education Department of the Government of the Basque Country (PRE_2016_1_0057, PRE_2017_2_0224, PRE_2018_2_0057), the University of Granada Plan Propio de Investigacion 2016-Excellence actions: Unit of Excellence on Exercise and Health (UCEES), and Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades (FEDER, ref. SOMM17/6107/UGR).

Introduction: Hepatic steatosis also known as fatty liver is due to abnormal and excessive accumulation of lipids with in hepatocytes. It is the most common chronic disease of liver. Magnetic resonance techniques can detect fatty liver more accurately than ultrasonography and become primary modalityto assess hepatic steatosis both quantitatively and qualitatively. Aims: The aims of this study were detection and quantification of liver fat by MR technique in patients of hepatic steatosis. Comparison of USG and MRI in detection and quantification of liver fat. Material and Methods: This cross-sectional study was carried out on 50 patients in Department of Radiodiagnosis, Government Medical College, Rajindra Hospital, Patiala in whom risk factors for hepatic steatosis were present. Considering T1 Dixon MRI of liver as reference its comparison with USG was done in these patients for detection of hepatic steatosis and quantification of liver fat. Results: USG had sensitivity 73.68%, specificity 66.67%, positive predictive value 87.50% and negative predictive value 44.44% as compared to MRI T1 Dixon sequence for detection of fatty liver. When grading of fatty liver on USG was compared with percentage quantification of liver fat on MRI T1 Dixon sequence of liver, there was considerable overlapping of fat percentage in each grade. Conclusion: Advantages of MRI as compared to USG is its more sensitivity and specificity for detection of hepatic steatosis, early detection of hepatc steatosis, quantify liver fat, objective and not observer dependent.

Fermented milk beverage is a product containing milk, whey and/or other ingredients, fermented by specific microorganisms and/or added with fermented milks. Fat determination in this product is important to quality control and inspection. The Gerber method is used worldwide as a simple and rapid method for fat content analysis in raw and processed milks. In Brazil, Roese-Gottlieb is the official method for analysis of fat content in milk beverages. However, the use of Gerber method for fat content determination in fermented milk beverages is widespread throughout the industry in the country. Several authors have tested the use of Gerber method for some dairy products, but there is no report on this evaluation for fermented milk beverages. In this context, the objectives of this work were to determine the fat content of fermented milk beverages by the Gerber method and evaluate the performance of this test, using Roese-Gottlieb as a reference method. Thirty samples of fermented milk beverages were analyzed by both methods. The fat contents ranged from 1.25 to 2.40% by the Gerber method and from 1.24 to 2.50% by the Roese-Gottlieb method. There was no difference (p > 0.05) between the methods. The Gerber method can be used to determine the fat content of fermented milk beverages, without prejudice to the results obtained.

Portuguese dry fermented sausages are traditionally processed through direct drying/smoking, making them susceptible to polycyclic aromatic hydrocarbons (PAHs) contamination. The purpose of this study was to assess the effect of added fat (20% and 40%), casing type (hog and collagen) and smoking procedures (direct and indirect exposure) on the 16 EPA priority PAHs in dry fermented sausages manufactured according traditional processing. The total PAHs content (sum of 16 PAHs) found in whole product (casing included) varied between 150 and 870 lg kg 1, with more than 99% of this content corresponding to harmless low molecular weight compounds. Concerning benzo(a)pyrene (BaP) and PAH4, the respective maximum contents (0.32 and 10.35 lg kg 1, respectively) did not exceed the imposed limits regulated by the European Union. According to our results, casing type was the most influential factor. For hog samples, fat content and smoking regime alone did not influenced the total PAHs amount. However, significantly higher (p < 0.05) contamination levels were detected in hog casing samples combining high fat content and direct smoking procedures. In opposition, irrespective of the fat content and smoking regime, safer products, with significantly lower (p < 0.001) contamination levels, were obtained when collagen casing was used.