NAFLD: Mechanisms, Treatments, and Biomarkers

被引:211
作者
Nassir, Fatiha [1 ]
机构
[1] Univ Missouri, Dept Med, Div Gastroenterol & Hepatol, Columbia, MO 65212 USA
关键词
non-alcoholic fatty liver disease (NAFLD); metabolic-associated fatty liver disease (MAFLD); non-alcoholic steatohepatitis (NASH); metabolic-associated steatohepatitis (MASH); liver; mitochondria; sirtuins; lipotoxicity; reactive oxygen species (ROS); biomarkers; NONALCOHOLIC FATTY LIVER; DE-NOVO LIPOGENESIS; MITOCHONDRIAL QUALITY-CONTROL; TRIGLYCERIDE TRANSFER PROTEIN; HEPATIC CD36 EXPRESSION; LIFE-STYLE MODIFICATION; LONG NONCODING RNAS; INSULIN-RESISTANCE; ACID OXIDATION; ADIPOSE-TISSUE;
D O I
10.3390/biom12060824
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic-associated fatty liver disease (MAFLD), is one of the most common causes of liver diseases worldwide. NAFLD is growing in parallel with the obesity epidemic. No pharmacological treatment is available to treat NAFLD, specifically. The reason might be that NAFLD is a multi-factorial disease with an incomplete understanding of the mechanisms involved, an absence of accurate and inexpensive imaging tools, and lack of adequate non-invasive biomarkers. NAFLD consists of the accumulation of excess lipids in the liver, causing lipotoxicity that might progress to metabolic-associated steatohepatitis (NASH), liver fibrosis, and hepatocellular carcinoma. The mechanisms for the pathogenesis of NAFLD, current interventions in the management of the disease, and the role of sirtuins as potential targets for treatment are discussed here. In addition, the current diagnostic tools, and the role of non-coding RNAs as emerging diagnostic biomarkers are summarized. The availability of non-invasive biomarkers, and accurate and inexpensive non-invasive diagnosis tools are crucial in the detection of the early signs in the progression of NAFLD. This will expedite clinical trials and the validation of the emerging therapeutic treatments.
引用
收藏
页数:32
相关论文
共 313 条
[11]   Nonalcoholic fatty liver disease [J].
Brunt, Elizabeth M. ;
Wong, Vincent W. -S. ;
Nobili, Valerio ;
Day, Christopher P. ;
Sookoian, Silvia ;
Maher, Jacquelyn J. ;
Bugianesi, Elisabetta ;
Sirlin, Claude B. ;
Neuschwander-Tetri, BrentA. ;
Rinella, Mary E. .
NATURE REVIEWS DISEASE PRIMERS, 2015, 1
[12]   Long Non-Coding RNAs Involved in Progression of Non-Alcoholic Fatty Liver Disease to Steatohepatitis [J].
Atanasovska, Biljana ;
Rensen, Sander S. ;
Marsman, Glenn ;
Shiri-Sverdlov, Ronit ;
Withoff, Sebo ;
Kuipers, Folkert ;
Wijmenga, Cisca ;
van de Sluis, Bart ;
Fu, Jingyuan .
CELLS, 2021, 10 (08)
[13]   NAMPT and NAPRT: Two Metabolic Enzymes With Key Roles in Inflammation [J].
Audrito, Valentina ;
Messana, Vincenzo Gianluca ;
Deaglio, Silvia .
FRONTIERS IN ONCOLOGY, 2020, 10
[14]   Effects of different exercise modalities on novel hepatic steatosis indices in overweight women with type 2 diabetes [J].
Banitalebi, Ebrahim ;
Faramarzi, Mohammad ;
Nasiri, Samira ;
Mardaniyan, Majid ;
Rabiee, Vahid .
CLINICAL AND MOLECULAR HEPATOLOGY, 2019, 25 (03) :294-304
[15]   SIRT3 is regulated by nutrient excess and modulates hepatic susceptibility to lipotoxicity [J].
Bao, Jianjun ;
Scott, Iain ;
Lu, Zhongping ;
Pang, Liyan ;
Dimond, Christopher C. ;
Gius, David ;
Sack, Michael N. .
FREE RADICAL BIOLOGY AND MEDICINE, 2010, 49 (07) :1230-1237
[16]   Characterization of the Murine SIRT3 Mitochondrial Localization Sequence and Comparison of Mitochondrial Enrichment and Deacetylase Activity of Long and Short SIRT3 Isoforms [J].
Bao, Jianjun ;
Lu, Zhongping ;
Joseph, Joshua J. ;
Carabenciov, Darin ;
Dimond, Christopher C. ;
Pang, Liyan ;
Samsel, Leigh ;
Mccoy, J. Philip, Jr. ;
Leclerc, Jaime ;
Nguyen, PhuongMai ;
Gius, David ;
Sack, Michael N. .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2010, 110 (01) :238-247
[17]   SIRT3 deficiency exacerbates fatty liver by attenuating the HIF1α-LIPIN 1 pathway and increasing CD36 through Nrf2 [J].
Barroso, Emma ;
Rodriguez-Rodriguez, Rosalia ;
Zarei, Mohammad ;
Pizarro-Degado, Javier ;
Planavila, Anna ;
Palomer, Xavier ;
Villarroya, Francesc ;
Vazquez-Carrera, Manuel .
CELL COMMUNICATION AND SIGNALING, 2020, 18 (01)
[18]   Subcutaneous delivery of FGF21 mRNA therapy reverses obesity, insulin resistance, and hepatic steatosis in diet-induced obese mice [J].
Bartesaghi, Stefano ;
Wallenius, Kristina ;
Hovdal, Daniel ;
Liljeblad, Mathias ;
Wallin, Simonetta ;
Dekker, Niek ;
Barlind, Louise ;
Davies, Nigel ;
Seeliger, Frank ;
Winzell, Maria Sorhede ;
Patel, Sima ;
Theisen, Matt ;
Brito, Luis ;
Bergenhem, Nils ;
Andersson, Shalini ;
Peng, Xiao-Rong .
MOLECULAR THERAPY-NUCLEIC ACIDS, 2022, 28 :500-513
[19]  
BASS NM, 1990, MOL CELL BIOCHEM, V98, P167
[20]   Properties of the permeability transition pore in mitochondria devoid of cyclophilin D [J].
Basso, E ;
Fante, L ;
Fowlkes, J ;
Petronilli, V ;
Forte, MA ;
Bernardi, P .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (19) :18558-18561