scholarly journals Decreased Sclerostin Secretion in Humans and Mice With Nonalcoholic Fatty Liver Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Fangli Zhou ◽  
Yan Wang ◽  
Yujue Li ◽  
Mengjia Tang ◽  
Shan Wan ◽  
...  

ObjectivesGrowing evidence argues for a relationship between liver and bone metabolisms. Sclerostin is a secreted glycoprotein and could antagonize osteoblast-mediated bone formation. Previous studies indicated that circulating sclerostin levels may be associated with metabolic parameters with inconsistent results. This study was designed to evaluate serum sclerostin in patients with or without nonalcoholic fatty liver disease (NAFLD) and to analyze its relationship with metabolic parameters in different populations.MethodsA cross-sectional study was designed and 168 NAFLD subjects and 85 control subjects were included in this study. Serum sclerostin and metabolic parameters were measured. Mouse models of NAFLD were also induced by high-fat diet. Bone structural parameters were determined using microCT and mRNA expression levels of sclerostin in bone and liver tissues were measured.ResultsOur study suggested that circulating sclerostin levels were significantly lower in NAFLD subjects compared with normal controls. In NAFLD subjects, sclerostin was negatively correlated with multiple metabolic parameters, including waist circumference, urea, hepatic enzyme, gamma-glutamyl transpeptidase, and triglyceride, while such correlation was not significant in control subjects. Circulating sclerostin was also negatively correlated with fatty liver index in NAFLD subjects but not in control subjects. Mice fed on a high-fat diet had reduced bone mass and lower sclerostin expression levels in both the bone and liver tissues.ConclusionsOur study suggested that the liver-lipid-bone interactions may play a key role in the abnormal bone metabolism in NAFLD, and circulating sclerostin may be a surrogate marker to reflect bone metabolism status in NAFLD subjects.

Aging ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 8960-8974
Author(s):  
Xiaoli Qian ◽  
Ting Wang ◽  
Jiahong Gong ◽  
Li Wang ◽  
Xuyan Chen ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Doo Jin Choi ◽  
Seong Cheol Kim ◽  
Gi Eun Park ◽  
Bo-Ram Choi ◽  
Dae Young Lee ◽  
...  

The present study aimed to evaluate the potential synergistic and protective effects of ALM16, a mixture of Astragalus membranaceus (AM) and Lithospermum erythrorhizon (LE) extract in a ratio of 7 : 3, against hepatic steatosis in high fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) mice. Forty-eight mice were randomly divided into eight groups and orally administered daily for 6 weeks with a normal diet (ND) or high fat diet alone (HFD), HFD with AM (HFD + 100 mg/kg AM extract), HFD with LE (HFD + 100 mg/kg LE extract), HFD with ALM16 (HFD + 50, 100, and 200 mg/kg ALM16), or HFD with MT (HFD + 100 mg/kg Milk thistle extract) as a positive control. ALM16 significantly decreased the body and liver weight, serum and hepatic lipid profiles, including triglyceride (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL), and low-density lipoprotein-cholesterol (LDL), and serum glucose levels, compared to the HFD group. Moreover, ALM16 significantly ameliorated the HFD-induced increased hepatic injury markers, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and gamma-glutamyltransferase (GGT)-1. Furthermore, as compared to the mice fed HFD alone, ALM16 increased the levels of phosphorylated AMP-activated protein kinase (p-AMPK) and acetyl-CoA carboxylase (p-ACC), thereby upregulating the expression of carnitine palmitoyltransferase (CPT)-1 and downregulating the expression of sterol regulatory element-binding protein (SREBP)-1c and fatty acid synthase (FAS). These results demonstrated that ALM16 markedly inhibited HFD-induced hepatic steatosis in NAFLD mice by modulating AMPK and ACC signaling pathways, and may be more effective than the single extracts of AM or LE.


Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 3067 ◽  
Author(s):  
Leonardo Recena Aydos ◽  
Luane Aparecida do Amaral ◽  
Roberta Serafim de Souza ◽  
Ana Cristina Jacobowski ◽  
Elisvânia Freitas dos Santos ◽  
...  

Researchers have a range of animal models in which to study Nonalcoholic fatty liver disease (NAFLD). Induction of NAFLD by a high-fat diet in the C57BL/6 strain is the most widely used among mice. In this study, we review works that performed NAFLD induction by a high-fat diet using the C57BL/6 strain, focusing on experiments on the effects of lipid ingestion. Studies are initially distinguished into researches in which mice received lipids by oral gavage and studies in which lipid was added to the diet, and each of these designs has peculiarities that must be considered. Oral gavage can be stressful for animals and needs trained handlers but allows accurate control of the dose administered. The addition of oils to the diet can prevent stress caused to mice by gavage, but possible changes in the consistency, taste, and smell of the diet should be considered. Regarding the experimental design, some variables, such as animal sex, treatment time, and diet-related variables, appear to have a definite pattern. However, no pattern was found regarding the number of animals per group, age at the beginning of the experiment, time of adaptation, the substance used as a vehicle, and substance used as a control.


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