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High-fat diet (HFD)-induced insulin resistance (IR) in skeletal muscle is often accompanied by mitochondrial dysfunction and oxidative stress. Boosting nicotinamide adenine dinucleotide (NAD) using nicotinamide riboside (NR) can effectively decrease oxidative stress and increase mitochondrial function. However, whether NR can ameliorate IR in skeletal muscle is still inconclusive. We fed male C57BL/6J mice with an HFD (60% fat) 400 mg/kgbw NR for 24 weeks. C2C12 myotube cells were treated with 0.25 mM palmitic acid (PA) 0.5 mM NR for 24 h. Indicators for IR and mitochondrial dysfunction were analyzed. NR treatment alleviated IR in HFD-fed mice with regard to improved glucose tolerance and a remarkable decrease in the levels of fasting blood glucose, fasting insulin and HOMA-IR index. NR-treated HFD-fed mice also showed improved metabolic status regarding a significant reduction in body weight and lipid contents in serum and the liver. NR activated AMPK in the skeletal muscle of HFD-fed mice and PA-treated C2C12 myotube cells and upregulated the expression of mitochondria-related transcriptional factors and coactivators, thereby improving mitochondrial function and alleviating oxidative stress. Upon inhibiting AMPK using Compound C, NR lost its ability in enhancing mitochondrial function and protection against IR induced by PA. In summary, improving mitochondrial function through the activation of AMPK pathway in skeletal muscle may play an important role in the amelioration of IR using NR., High-fat diet (HFD)-induced insulin resistance (IR) in skeletal muscle is often accompanied by mitochondrial dysfunction and oxidative stress. Boosting nicotinamide adenine dinucleotide (NAD) using nicotinamide riboside (NR) can effectively decrease oxidative stress and increase mitochondrial function. However, whether NR can ameliorate IR in skeletal muscle is still inconclusive. We fed male C57BL/6J mice with an HFD (60% fat) ± 400 mg/kg·bw NR for 24 weeks. C2C12 myotube cells were treated with 0.25 mM palmitic acid (PA) ± 0.5 mM NR for 24 h. Indicators for IR and mitochondrial dysfunction were analyzed. NR treatment alleviated IR in HFD-fed mice with regard to improved glucose tolerance and a remarkable decrease in the levels of fasting blood glucose, fasting insulin and HOMA-IR index. NR-treated HFD-fed mice also showed improved metabolic status regarding a significant reduction in body weight and lipid contents in serum and the liver. NR activated AMPK in the skeletal muscle of HFD-fed mice and PA-treated C2C12 myotube cells and upregulated the expression of mitochondria-related transcriptional factors and coactivators, thereby improving mitochondrial function and alleviating oxidative stress. Upon inhibiting AMPK using Compound C, NR lost its ability in enhancing mitochondrial function and protection against IR induced by PA. In summary, improving mitochondrial function through the activation of AMPK pathway in skeletal muscle may play an important role in the amelioration of IR using NR.

Jie Pan,1 Qiuyan Li,1 Yan Sun,1 Yingying Gu,1 Yijie Ding,1 Nengzhi Pang,1 Yujia Zhou,1 Lei Pei,1 Mengqi Gao,1 Sixi Ma,1 Ying Xiao,1 Feilong Wu,1 De Hu,1 Yu-Ming Chen,2 Lili Yang1 1Department of Nutrition, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, People’s Republic of ChinaCorrespondence: Lili Yang, Department of Nutrition, School of Public Health, Sun Yat-sen University, No. 74, Zhongshan Road 2, Yuexiu District, Guangzhou, Guangdong, 510080, People’s Republic of China, Tel +86-20-87330625, Email yangll7@mail.sysu.edu.cnPurpose: A panel of international experts proposed a new definition of fatty liver in 2020, namely metabolic dysfunction-associated fatty liver disease (MAFLD). As an adipokine, adipsin is closely related to metabolic-related diseases. In this study, we aimed to evaluate the relationship among MAFLD, serum adipsin, and metabolic risk abnormalities.Methods: Our study was a cross-sectional study based on the first follow-up of the Guangzhou Nutrition and Health Study (GNHS). A total of 908 patients with hepatic steatosis were involved in our study. Detailed data of patients were collected based upon questionnaire information, physical examination, and blood biochemical test.Results: Among the 908 patients, 789 patients were diagnosed with MAFLD. The levels of serum adipsin in the MAFLD group and non-MAFLD group were (3543.00 (3187.94– 3972.50) ng/mL) and (3095.33 (2778.71– 3354.77) ng/mL) (P < 0.001), respectively. After adjusting for potential confounders, adipsin levels were found to be associated with MAFLD. The OR was 3.46 (95% CI: 1.57– 7.64) for adipsin when comparing subjects in the highest tertile with those in the lowest tertile. With the increase in the number of metabolic risk abnormalities, both the levels of serum adipsin and

Qinglei Kong,1,* Jianhua Han,1,* Hong Deng,2 Feilong Wu,1 Shaozhong Guo,2 Zhiqiang Ye1 1Department of Emergency, The Third Affiliated Hospital of Sun Yat-San University, Guangzhou 510630, China; 2Department of Infectious Disease and Clinical Laboratory, The Third Affiliated Hospital of Sun Yat-San University, Guangzhou 510630, China *These authors contributed equally to this work Objective: MicroRNA (miR)-431 plays an essential role in various human cancer types, particularly in the process of invasion. However, the function and mechanism of miR-431-5p in the invasion of hepatocellular carcinoma (HCC) remain undefined.Methods: The expression levels of miR-431-5p and its potential target protein UROC28 in hepatocellular carcinoma cells and tissues were detected, and the levels of EMT markers in vivo and in vitro were also detected.Results: MiR-431-5p was downregulated in HCC cell lines and tissues and associated with vascular invasion and tumor encapsulation. Furthermore, miR-431-5p was able to influence the epithelialto- mesenchymal transition (EMT) process in HCCLM3 and HUH7 cells. Mechanistically, it was discovered that miR-431-5p repressed invasion by targeting UROC28. Furthermore, miR-431-5p influenced the EMT markers in HCCLM3 and HUH7 cells by downregulating UROC28 expression. Similarly, in vivo assays confirmed that miR-431-5p upregulation in HCC cells remarkably inhibited tumor proliferation and influenced the EMT markers.Conclusion: The current study has demonstrated that the miR-431-5p/UROC28 axis acts possible influence on the EMT in HCC. Upregulation of miR-431-5p could be an original approach for inhibiting tumor invasion. Keywords: hepatocellular carcinoma, microRNA-431, UROC28, PBOV1, epithelial-to-mesenchymal transition