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Background/purpose: Metabolic associated fatty liver disease (MAFLD) was proposed as a new definition to put emphasis on the metabolic aspects of nonalcoholic fatty liver disease (NAFLD). We aim to compare the cardiovascular and renal burden between MAFLD and NAFLD patients., Methods: 12183 participants were enrolled in East China. The cardiovascular burden (Framingham risk score and previous cardiovascular diseases (CVD)) and renal burden (eGFR and chronic kidney disease (CKD)) were measured., Results: The risk of hypertension, dyslipidemia, diabetes, overweight/obesity, and central obesity of MAFLD patients were higher than those of NAFLD. Patients with MAFLD have a similar or higher beta coefficients in Framingham risk score [beta (95%CI): male 0.062 (0.055,0.069) vs 0.041 (0.033,0.048); female 0.014 (0.012,0.016) vs 0.012 (0.01,0.014)], and higher odds ratio in previous CVD [odds ratio (95%CI): male 1.50 (1.22,1.85) vs 1.35 (1.1,1.66); female 1.58 (1.33,1.87) vs 1.45 (1.22,1.72)], compared with those with NAFLD. However, compared with males with MAFLD, the odds ratio of CKD was higher in those with NAFLD [eGFR: -2.731 (-3.422, -2.041) vs-3.578 (-4.268, -2.887). CKD: 1.44 (1.05,1.96) vs 1.56 (1.14,2.12)]. In female, CKD was only marginally associated with NAFLD [0.8 (0.62,1.02), P=0.075], but not MAFLD [0.87 (0.68,1.11), P=0.268]., Conclusions: Patients with MAFLD have a similar or higher risk of future and previous CVD compared with those with NAFLD, but the risk of CKD was higher in male with NAFLD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Yu, Zhang, Chen, Wan, Chen, Xia, Yu, Wang, Ye and Lu.)

Background and Aim: Non-alcoholic fatty liver disease (NAFLD) is associated with incident type 2 diabetes; however, the extent to which NAFLD may confer its risk remains uncertain, especially in Europeans. Emerging evidence suggests that sleep behaviors are linked to NAFLD and diabetes. We aimed to measure whether sleep behaviors modified the association between NAFLD and incident type 2 diabetes., Methods: This prospective cohort study included 365 339 participants without type 2 diabetes at baseline in UK Biobank data. Five sleep behaviors, including sleep duration, insomnia, snoring, chronotype, and daytime sleepiness, were collected from the questionnaire. Overall sleep patterns were created by summing the five scores. Liver steatosis was based on the fatty liver index., Results: During a median follow up of 11.0 years, we documented 8774 patients with incident type 2 diabetes. NAFLD was significantly associated with increased diabetes risk. Sleeping 7-8 h/day, no insomnia, no self-reported snoring, and no frequent daytime sleepiness were independently associated with incident type 2 diabetes, with a 20%, 18%, 16%, and 31% lower risk, respectively. About 33.8% and 33.5% of type 2 diabetes events in this cohort could be attributed to NAFLD and poor sleep pattern, respectively. Participants with NAFLD and poor sleep pattern showed the highest risk of type 2 diabetes (relative risk 3.17, 95% confidence interval 2.80, 3.59). Sleep pattern (healthy, intermediate, and poor) did not significantly modify the association between NAFLD and type 2 diabetes. However, when studying separately, we found a significant interaction between NAFLD and insomnia on the risk of incident type 2 diabetes (P for interaction = 0.003)., Conclusion: In this large prospective study, both NAFLD and some sleep behaviors were risk factors for type 2 diabetes. Although overall sleep pattern did not modify the association between NAFLD and type 2 diabetes, certain sleep behavior, especially insomnia, showed the modification effect., (© 2022 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Lead (Pb) has been suggested as an endocrine-disrupting chemical. However, few studies have investigated the association between chronic Pb exposure and fatty liver disease., Objectives: We aimed to investigate the association of chronic Pb exposure with fatty liver disease and whether the variations of the gut microbiota involve in the mechanism of the fatty liver disease induced by chronic Pb exposure., Methods: We conducted a cross-sectional study of 3066 rural participants in East China. Blood lead level (BLL) was detected, and abdominal ultrasonography was used to diagnose hepatic steatosis. Both the definition of non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) were used. Wistar rats were randomly divided into two groups and each group was exposed to 0 or 0.05% w/v Pb through drinking water for 28 weeks. The relevant parameters of hepatic lipid metabolism and gut microbiota were analyzed., Results: In humans, after adjusting for potential confounders, the odds of having NAFLD and MAFLD were significantly increased by 54% and 52% in the participants in the fourth BLL quartile (OR 1.54, 95% CI 1.24, 1.91 and OR 1.52, 95% CI 1.22, 1.89). In the rats, chronic Pb exposure induced the increased visceral fat, hepatic steatosis, and dysbiosis of the gut microbiota, including the decrease of richness, diversity, evenness and phylogenetic diversity of the gut microbiota and the significant alternations of the gut microbiota composition, particularly, the decrease of the relative abundance of Coprococcus and Oscillospira at the genus level., Conclusions: Chronic Pb exposure could induce fatty liver disease, which may be associated with the variations of the gut microbiota., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Non-alcoholic fatty liver disease (NAFLD) is a common disease with a multitude of complications. Increasing evidence shows that the dietary supplement with betaine, a natural chemical molecule, can effectively reduce the fat accumulation in the liver. Translational regulation is considered to play a vital role in gene expression, but whether betaine functions through the regulation of gene translational level is still unclear. To this end, RNC-seq (mRNAs bound to ribosome-nascent chain complex sequencing) and RNA-seq co-analyses were performed to identify betaine target genes by using the liver samples from high-fat diet adding betaine treated and high-fat diet treated mice. The results showed that betaine does play a lipid-lowering role by regulating the expression of gene translation levels; some NAFLD- and lipid metabolism-associated genes were differentially expressed at translational level, for example. And the translation ratio (TR) of gene significantly increased after betaine treatment. Finally, we identified a novel function gene, Gpc1, which may mediate the lipid-lowering effect of betaine in the liver. To sum up, this study depicted the molecular portrait of mice liver with or without betaine treatment from the angel of translatome and transcriptome, giving insights into the molecular mechanism of betaine-mediated lipid-lowering effect and also providing new clues for understanding and prevention of NAFLD., Competing Interests: Declaration of competing interest Authors declare that there is no conflict of interest or any competing financial interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background and Purpose: Non‐alcoholic fatty liver disease (NAFLD) affects over 25% of the general population and lacks an effective treatment. Recent evidence implicates disrupted mitochondrial calcium homeostasis in the pathogenesis of hepatic steatosis. Experimental Approach: In this study, mitochondrial calcium uniporter (MCU) was inhibited through classical genetic approaches, viral vectors or small molecule inhibitors in vivo to study its role in hepatic steatosis induced by high‐fat diet (HFD). In vitro, MCU was overexpressed or inhibited to change mitochondrial calcium homeostasis, endoplasmic reticulum–mitochondrial linker was adopted to increase mitochondria‐associated membranes (MAMs) and MICU1‐EF hand mutant was used to decrease the sensitivity of mitochondrial calcium uptake 1 (MICU1) to calcium and block MCU channel. Key Results: Here, we found that inhibition of liver MCU by AAV virus and classical genetic approaches can prevent HFD‐induced liver steatosis. MCU regulates mitochondrial calcium homeostasis and affects lipid accumulation in liver cells. In addition, a HFD in mice enlarged the MAM. The high‐calcium environment produced by MAM invalidated the function of MICU1 and led to persistent open of MCU channels. Therefore, it caused mitochondrial calcium overload and liver fat deposition. Inhibition of MAM and MCU alleviated HFD‐induced hepatic steatosis. MCU inhibitors (Ru360 and mitoxantrone) can block MCU channels and reduce mitochondrial calcium levels. Intraperitoneal injection of MCU inhibitors (0.01‐μM·kg−1 bodyweight) can alleviate HFD‐induced hepatic steatosis. Conclusion and Implications: These findings provide molecular insights into the way HFD disrupts mitochondrial calcium homeostasis and identify MCU as a promising drug target for the treatment of hepatic steatosis. [ABSTRACT FROM AUTHOR]