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[Display omitted] • Rutin showed the most potent AGEs inhibitory capacity in both food and HepG2 cell models. • Rutin mitigated glucose metabolism disorders induced by AGEs in HepG2 cells. • Rutin alleviated AGEs-induced insulin resistance via SOCS3/IRS1 and PI3K/AKT pathways. • PI3K/AKT pathway played an important role in enhancing insulin sensitivity in response to rutin. The accumulation of advanced glycosylation end products (AGEs) from food in the body disrupts normal physiological insulin activity and causes insulin resistance. This study compared the effects of ten types of polyphenols on AGEs production in both chemical and food models. It also investigated the impact of polyphenols on AGEs-induced insulin resistance in HepG2 cell models. Results showed that luteolin had the strongest inhibitory effect on fluorescent AGEs in the three chemical models. Rutin exhibited the most potent capacity to inhibit AGEs in biscuit models. Moreover, rutin alleviated the glucose metabolism disorders induced by representative AGEs (methylglyoxal-modified bovine serum albumin, MGO-BSA) in HepG2 cells. Mechanistic studies revealed that rutin could inhibit the phosphorylation of insulin receptor substrate 1 (IRS1) and the activity of suppressor of cytokine signaling 3 (SOCS3), while activating the phosphorylation of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) to alleviate the MGO-BSA-induced insulin resistance in HepG2 cells. [ABSTRACT FROM AUTHOR]

Segmentation of abdominal adipose tissues (AAT) into subcutaneous adipose tissues (SAT) and visceral adipose tissues (VAT) is of crucial interest for managing the obesity. Previous methods with raw or hand-crafted features rarely work well on large-scale subject cohorts, because of the inhomogeneous image intensities, artifacts and the diverse distributions of VAT. In this paper, we propose a novel two-stage coarse-to-fine algorithm for AAT segmentation. In the first stage, we formulate the AAT segmentation task as a pixel-wise classification problem. First, three types of features, intensity, spatial and contextual features, are extracted. Second, a new type of deep neural network, named multi-scale deep neural network (MSDNN), is provided to extract high-level features. In the second stage, to improve the segmentation accuracy, we refine coarse segmentation results by determining the internal boundaries of SAT based on coarse segmentation results and the continuous of SAT internal boundaries. Finally, we demonstrate the efficacy of our algorithm for both 2D and 3D cases on a wide population range. Compared with other algorithms, our method is not only more suitable for large-scale dataset, but also achieves better segmentation results. Furthermore, our system takes about 2 s to segment an abdominal image, which implies potential clinical applications. [ABSTRACT FROM AUTHOR]

Background & Aims: Fibroblast growth factor 21 (FGF21), a hormone predominantly secreted by the liver, has been shown to be positively associated with the severity of non-alcoholic fatty liver disease (NAFLD) in cross-sectional studies. We investigated the prospective association of FGF21 with NAFLD development in a 3-year prospective study involving a population-based cohort comprising 808 Chinese subjects. Methods: Serum FGF21 levels at baseline and follow-up were measured using an enzyme-linked immunosorbent assay. Independent predictors of NAFLD development were identified using multiple logistic regressions. The predicting accuracy of the models was evaluated using area under the receiver-operating characteristic (ROC) curves (AUCs). Results: In subjects who had progressed to NAFLD, the baseline FGF21 concentration (319.12pg/ml [172.65, 518.78]) was significantly higher than that in subjects who did not develop NAFLD (199.10pg/ml [123.56, 322.80]) (p <0.001). At follow-up, significant increase of FGF21 level was observed in those subjects who developed NAFLD (p <0.05). Baseline FGF21 was an independent predictor of NAFLD (OR: 7.102 [95% CI 2.488–20.270]; p <0.001), together with body mass index (BMI) (OR: 1.489 [95% CI 1.310–1.691]; p <0.001). The ROC-AUC was 0.816 (95% CI 0.766–0.867) for the FGF21 Model, which was calculated with FGF21 and BMI. FGF21 Model <0.13 can be used to rule out (sensitivity=85.71%, negative likelihood ratio=0.23) and ⩾0.30 can be rule in (specificity=86.34%, positive likelihood ratio=3.66) ultrasonography-diagnosed NAFLD after 3years. Conclusions: High serum FGF21 concentration was an independent predictor of NAFLD in humans. The FGF21 Model and its cut-offs may be useful for early diagnosis and intervention of NAFLD. [ABSTRACT FROM AUTHOR]

Background & Aims: Fibroblast growth factor 21 (FGF21), a hormone primarily secreted by the liver in response to peroxisome proliferator-activated receptor-α (PPARα) activation, has recently been shown to possess beneficial effects on lipid metabolism and hepatic steatosis in animal models. This study investigated the association of FGF21 with nonalcoholic fatty liver disease (NAFLD) in Chinese patients. Methods: Serum FGF21 levels were determined by enzyme-linked immunosorbent assay (ELISA) in 224 NAFLD and 124 control subjects, and their association with parameters of adiposity, glucose, and lipid profiles and levels of liver injury markers was studied. Besides serum concentrations, the mRNA expression of FGF21 in the liver tissue was also quantified by real-time PCR in 17 subjects with different degrees of steatosis, and was correlated with the levels of intrahepatic lipid. The protein levels of FGF21 were determined by quantitative ELISA. Results: Serum FGF21 levels in patients with NAFLD (402.38pg/ml [242.03, 618.25]) were significantly higher than those in control subjects (198.62pg/ml [134.96, 412.62]) (p <0.01). In human liver tissues, FGF21 mRNA expression increased with the degree of steatosis. Both FGF21 mRNA expression and serum FGF21 concentrations were positively correlated with intrahepatic triglyceride (TG) having r =0.692 and r =0.662, respectively, at p <0.01. Furthermore, the increased expression of FGF21 was accompanied by elevated protein levels in liver tissues. Conclusions: These results support the role of FGF21 as a key regulator of hepatic lipid metabolism in humans, and suggest that serum FGF21 can be potentially used as a biomarker for NAFLD. [ABSTRACT FROM AUTHOR]

Hyocholic acid (HCA) and its derivatives are found in trace amounts in human blood but constitute approximately 76% of the bile acid (BA) pool in pigs, a species known for its exceptional resistance to type 2 diabetes. Here, we show that BA depletion in pigs suppressed secretion of glucagon-like peptide-1 (GLP-1) and increased blood glucose levels. HCA administration in diabetic mouse models improved serum fasting GLP-1 secretion and glucose homeostasis to a greater extent than tauroursodeoxycholic acid. HCA upregulated GLP-1 production and secretion in enteroendocrine cells via simultaneously activating G-protein-coupled BA receptor, TGR5, and inhibiting farnesoid X receptor (FXR), a unique mechanism that is not found in other BA species. We verified the findings in TGR5 knockout, intestinal FXR activation, and GLP-1 receptor inhibition mouse models. Finally, we confirmed in a clinical cohort, that lower serum concentrations of HCA species were associated with diabetes and closely related to glycemic markers. [Display omitted] • HCA is the primary BA in pigs, a species known for its exceptional resistance to T2DM • Serum HCA levels are inversely correlated with glucose levels in humans with T2DM • HCA exhibit strong effects on glucose regulation in the pig and diabetic mouse models • HCA promote GLP-1 secretion via simultaneously activating TGR5 and inhibiting FXR Pigs are routinely raised on obesogenic diets yet are resistant to the development of T2DM. Zheng et al. report that a group of bile acids, hyocholic acid and its derivatives (HCAs), the primary bile acids in pigs, are inversely correlated with glucose levels in subjects with T2DM. They further discover that HCAs promote GLP-1 production and secretion through a distinct TGR5 and FXR signaling mechanism. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of pathologies ranging from uncomplicated hepatic fat accumulation to a state of lobular inflammation and hepatocyte ballooning, known as non-alcoholic steatohepatitis (NASH). Currently, there are no reliable biomarkers or effective therapeutic options established for NAFLD. Nevertheless, there are several molecular targets in the pipeline, of which fibroblast growth factor 21 (FGF21) is one. FGF21 is secreted primarily from liver and has a plethora of metabolic functions. Pre-clinical and epidemiological studies indicate a relationship between circulating FGF21 levels and hepatic fat content in both mice and humans. Moreover, animal studies have clearly shown that aberrant FGF21 signalling is a key pathological step in the development and progression of NAFLD. A recent Phase II clinical trial demonstrated that administration of an FGF21 analogue significantly reduced hepatic fat in subjects with NASH. As such, FGF21 provides a novel target for future biomarker and therapeutic studies. This review appraises preclinical data to outline the current understanding of FGF21 function in both normal hepatic function and NAFLD. Epidemiological evidence is explored to delineate the relationship between circulating FGF21 levels and NAFLD in humans. Finally, we review the therapeutic effects of FGF21 in the treatment of NAFLD. • FGF21 is a key regulator of hepatic glucose and lipid metabolism. • FGF21 resistance increases fatty acid supply to the liver and reduces fatty acid utilisation. • Hepatic fatty acid accumulation promotes lipotoxicity. • Circulating FGF21 levels are elevated in patients with NAFLD. • FGF21 mimetics are effective at reducing hepatic steatosis and inflammation. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To determine the appropriate cutoffs for visceral fat area (VFA) measured by magnetic resonance imaging linking to risk of the metabolic syndrome (MetS) and the corresponding waist circumference in Chinese. Methods and results: Totally 1140 individuals (men 525, women 615) aged from 35 to 75 years were included. The components of the MetS were defined by International Diabetes Federation (IDF) and Chinese Diabetes Society (CDS) definition, respectively. Receive operating characteristic curve analyses were used to determine the appropriate cutoffs of VFA and corresponding waist circumference in the prediction of the MetS. The optimal VFA cutoff was near 80cm2 in identifying the MetS with two or more components but not including overweight/obesity by either of the two definitions in all subjects. There was no difference in men by ages while women aged <50 years tended to have lower VFA cutoff than those aged ≥50 years by the two definitions. The appropriate waist circumference cutoffs were 90cm in men and 85cm in women for the MetS. Conclusion: The optimal cutoff of waist circumference for abdominal obesity is 90cm for men and 85cm for women in Chinese. [Copyright &y& Elsevier]

• A framework for fundus image quality assessment filters the image with quality defects and provides visual feedback for real-time image reacquisition. • The proposed semi-tied adversarial discriminative domain adaptation model improves the generalization performance across different datasets with various distributions. • An efficient coarse-to-fine landmark detection (e.g. OD, fovea) is integrated into the architecture for robust quality assessment. • The DR grading task is improved with the proposed quality assessment preprocessing. Objective and quantitative assessment of fundus image quality is essential for the diagnosis of retinal diseases. The major factors in fundus image quality assessment are image artifact, clarity, and field definition. Unfortunately, most of existing quality assessment methods focus on the quality of overall image, without interpretable quality feedback for real-time adjustment. Furthermore, these models are often sensitive to the specific imaging devices, and cannot generalize well under different imaging conditions. This paper presents a new multi-task domain adaptation framework to automatically assess fundus image quality. The proposed framework provides interpretable quality assessment with both quantitative scores and quality visualization for potential real-time image recapture with proper adjustment. In particular, the present approach can detect optic disc and fovea structures as landmarks, to assist the assessment through coarse-to-fine feature encoding. The framework also exploit semi-tied adversarial discriminative domain adaptation to make the model generalizable across different data sources. Experimental results demonstrated that the proposed algorithm outperforms different state-of-the-art approaches and achieves an area under the ROC curve of 0.9455 for the overall quality classification. [ABSTRACT FROM AUTHOR]