Browsing by Subject "Fatty liver disease"

Now showing 1 - 4 of 4
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    Albumin Deficiency Reduces Hepatic Steatosis and Improves Glucose Metabolism in a Mouse Model of Diet-Induced Obesity
    (MDPI, 2023-04-25) Abdollahi, Afsoun; Narayanan, Sanjeev K.; Frankovich, Alexandra; Lai, Yen-Chun; Zhang, Yi; Henderson, Gregory C.; Anatomy, Cell Biology and Physiology, School of Medicine
    Serum albumin facilitates the transport of free fatty acids (FFAs) from adipose tissue to other organs. It was not known if impeding this process could protect from hepatic steatosis and metabolic dysfunction in obesity. We tested whether albumin knockout (Alb−/−) mice would exhibit a reduction in plasma FFA concentration, reduced hepatic lipid accumulation, and improved glucoregulation as compared to wild-type (WT) mice. Male homozygous albumin knockout mice (Alb−/−) and WT controls were fed a low-fat diet (LFD) or high-fat diet (HFD). Alb−/− mice exhibited a similar body weight gain and body composition as WT on both diets. Despite HFD-induced obesity, Alb−/− mice were protected from various comorbidities. Compared to WT mice on the HFD, Alb−/− exhibited lower plasma FFA levels, lower blood glucose levels during glucose tolerance and insulin tolerance tests, and lower hepatic steatosis and inflammation. Alb−/− mice on HFD also exhibited elevated expression of multiple genes in the liver and adipose tissues, such as peroxisome proliferator-activated receptor α in both tissues, as well as glucose transporter-4 and adiponectin in adipose tissues. The results indicate that albumin’s FFA transport function may be involved in the development of hepatic lipid accumulation and dysregulated glucose metabolism in obesity.
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    Autophagy in liver diseases: A matter of what to remove and whether to keep
    (KeAi Communications, 2018-09) Yin, Xiao-Ming; Pathology and Laboratory Medicine, School of Medicine
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    Pediatric Non-Alcoholic Fatty Liver Disease (NAFLD): Trends, Mortality, and Socioeconomic Disparities in the U.S., 1998–2020
    (MDPI, 2025-01-08) Wasuwanich, Paul; So, Joshua M.; Sadek, Mustafa; Jarasvaraparn, Chaowapong; Rajborirug, Songyos; Quiros-Tejeira, Ruben E.; Karnsakul, Wikrom; Pediatrics, School of Medicine
    Background/objectives: We aim to describe the changing inpatient epidemiology of NAFLD in the U.S. and identify major risk factors associated with mortality in the disease among hospitalized pediatric patients. Methods: Hospitalization data from the 1998-2020 National Inpatient Sample were utilized. ICD-9 and ICD-10 codes were used to identify pediatric patients (age less than 18 years old) with NAFLD, and risk factors for mortality were analyzed by logistic regression. Results: We identified 68,869 pediatric hospitalizations involving NAFLD. Among those, 970 (1.4%) died during hospitalization. Hospitalization rates have been rapidly increasing from 1998 to 2020 (incidence rate ratio (IRR): 1.07; 95% CI: 1.06-1.07; p < 0.001). There was a significant difference in mortality based on the type of hospital (rural, non-teaching urban, or teaching urban) in pediatric patients with NAFLD (p < 0.05). Coagulopathy was significantly associated with increased odds of mortality, while age ≥ 12 years, diabetes and obesity were associated with decreased odds of mortality (p < 0.05). Sex, race/ethnicity, hepatitis B, hepatitis C, HIV, and IV drug use were not significantly associated with mortality. Conclusions: Our study has shown ever increasing hospitalization rates for NAFLD in pediatric populations and well as significant risk factors associated with mortality. Further studies should be performed as more data on this patient population are collected.
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    Sestrin Proteins Protect Against Lipotoxicity-Induced Oxidative Stress in the Liver via Suppression of C-Jun N-Terminal Kinases
    (Elsevier, 2021) Fang, Zhigang; Kim, Hyeong-Geug; Huang, Menghao; Chowdhury, Kushan; Li, Ming O.; Liangpunsakul, Suthat; Dong, X. Charlie; Biochemistry and Molecular Biology, School of Medicine
    Background & aims: Sestrin 1/2/3 (Sesn1/2/3) belong to a small family of proteins that have been implicated in the regulation of metabolic homeostasis and oxidative stress. However, the underlying mechanisms remain incompletely understood. The aim of this work was to illustrate the collective function of Sesn1/2/3 in the protection against hepatic lipotoxicity. Methods: We used Sesn1/2/3 triple knockout (TKO) mouse and cell models to characterize oxidative stress and signal transduction under lipotoxic conditions. Biochemical, histologic, and physiological approaches were applied to illustrate the related processes. Results: After feeding with a Western diet for 8 weeks, TKO mice developed remarkable metabolic associated fatty liver disease that was manifested by exacerbated hepatic steatosis, inflammation, and fibrosis compared with wild-type counterparts. Moreover, TKO mice exhibited higher levels of hepatic lipotoxicity and oxidative stress. Our biochemical data revealed a critical signaling node from sestrins to c-Jun N-terminal kinases (JNKs) in that sestrins interact with JNKs and mitogen-activated protein kinase kinase 7 and suppress the JNK phosphorylation and activity. In doing so, sestrins markedly reduced palmitate-induced lipotoxicity and oxidative stress in both mouse and human hepatocytes. Conclusions: The data from this study suggest that Sesn1/2/3 play an important role in the protection against lipotoxicity-associated oxidative stress and related pathology in the liver.