scholarly journals Is HSD17B13 Genetic Variant a Protector for Liver Dysfunction? Future Perspective as a Potential Therapeutic Target

2021 ◽  
Vol 11 (7) ◽  
pp. 619
Author(s):  
Takashi Motomura ◽  
Sriram Amirneni ◽  
Ricardo Diaz-Aragon ◽  
Lanuza A. P. Faccioli ◽  
Michelle R. Malizio ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Therapeutic Target ◽  
Fatty Liver Disease ◽  
Genetic Variant ◽  
Association Studies ◽  
Future Perspective ◽  
Genome Wide Association Studies ◽  
Potential Therapeutic Target ◽  
Alcoholic Fatty Liver

As diet and lifestyle have changed, fatty liver disease (FLD) has become more and more prevalent. Many genetic risk factors, such as variants of PNPLA3, TM6SF2, GCKR, and MBOAT7, have previously been uncovered via genome wide association studies (GWAS) to be associated with FLD. In 2018, a genetic variant (rs72613567, T > TA) of hydroxysteroid 17-β dehydrogenase family 13 (HSD17B13) was first associated with a lower risk of developing alcoholic liver disease and non-alcoholic fatty liver disease (NAFLD) in minor allele carriers. Other HSD17B13 variants were also later linked with either lower inflammation scores among NAFLD patients or protection against NAFLD (rs6834314, A > G and rs9992651, G > A) respectively. HSD17B13 is a lipid droplet-associated protein, but its function is still ambiguous. Compared to the other genetic variants that increase risk for FLD, HSD17B13 variants serve a protective role, making this gene a potential therapeutic target. However, the mechanism by which these variants reduce the risk of developing FLD is still unclear. Because studies in cell lines and mouse models have produced conflicting results, human liver tissue modeling using induced pluripotent stem cells may be the best way to move forward and solve this mystery.

scholarly journals Lipid droplets associated perilipins protein insights into finding a therapeutic target approach to cure non-alcoholic fatty liver disease (NAFLD)

2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Aman Sharma
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Therapeutic Target ◽  
Fatty Liver Disease ◽  
Lipid Droplets ◽  
Alcoholic Fatty Liver ◽  
The World ◽  
Associated Proteins ◽  
Pharmacological Target ◽  
Alcoholic Fatty Liver Disease

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is now the most common form of chronic liver disease in the world, and it’s linked to a slew of other risk factors including diabetes, obesity, dysbiosis and inflammatory bowel disease. More than 30 years ago, a patient was diagnosed with fatty liver with excessive fat accumulation in hepatocytes, a disorder known as hepatosteatosis. There will be no promising therapeutic medicines available from 1980 to 2021 which can reverse the fatty liver to normal liver state. In this review, we highlighted on lipid droplet associated protein which play a major role in accumulation of fat in liver cells and how these cellular pathway could be a promising therapeutic approach to treat the fatty liver disease. Main body Over the last few decades, Western countries follow a high-fat diet and change their lifestyle pattern due to certain metabolic disorders prevalence rate is very high all over the world. NAFLD is a major health issue and burden globally nowadays. Researchers are trying to find out the potential therapeutic target to combat the disease. The exact pathophysiology of the disease is still unclear. In the present decades. There is no Food and Drug Administration approved drugs are available to reverse the chronic condition of the disease. Based on literature survey, lipid droplets and their associated protein like perilipins play an eminent role in body fat regulation. In this review, we explain all types of perilipins such as perilipin1-5 (PLIN1-5) and their role in the pathogenesis of fatty liver which will be helpful to find the novel pharmacological target to treat the fatty liver. Conclusion In this review, majorly focussed on how fat is get deposited into hepatocytes follow the cellular signalling involved during lipid droplet biogenesis and leads to NAFLD. However, up to date still there mechanism of action is unclear. In this review, we hypothesized that lipid droplets associated proteins like perilipins could be better pharmacological target to reverse the chronic stage of fatty liver disease and how these lipid droplets associated proteins hide a clue to maintain the normal lipid homeostasis in the human body.

scholarly journals Hepatic NAD+deficiency as a therapeutic target for non-alcoholic fatty liver disease in ageing

2016 ◽  
Vol 173 (15) ◽  
pp. 2352-2368 ◽  
Author(s):  
Can-Can Zhou ◽  
Xi Yang ◽  
Xia Hua ◽  
Jian Liu ◽  
Mao-Bing Fan ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Therapeutic Target ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

scholarly journals SIRT1 as a potential therapeutic target for treatment of nonalcoholic fatty liver disease

2011 ◽  
Vol 17 (5) ◽  
pp. HY5-HY9 ◽  
Author(s):  
Yasar Colak ◽  
Oguzhan Ozturk ◽  
Ebubekir Senates ◽  
Ilyas Tuncer ◽  
Elif Yorulmaz ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Therapeutic Target ◽  
Fatty Liver Disease ◽  
Potential Therapeutic Target ◽  
Nonalcoholic Fatty Liver

scholarly journals Genetic Contribution to Non-alcoholic Fatty Liver Disease and Prognostic Implications

2021 ◽  
Vol 21 (3) ◽  
Author(s):  
Katherine Martin ◽  
Anas Hatab ◽  
Varinder S. Athwal ◽  
Elliot Jokl ◽  
Karen Piper Hanley
Keyword(s):  
Liver Disease ◽  
Risk Stratification ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Complex Disease ◽  
Genetic Variant ◽  
Current Knowledge ◽  
Prognostic Models ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Abstract Purpose of Review Non-alcoholic fatty liver disease (NAFLD) is a major and increasing health burden, with the potential to overwhelm hepatology services. However, only a minority of patients develop advanced liver disease. The challenge is early identification of patients at risk of progression. This review aims to summarize current knowledge on the genetic predisposition to NAFLD, and its implications for prognostication and risk stratification. Recent Findings PNPLA3-I148M is the most robustly associated genetic variant with NAFLD. Recently, variants in TM6SF2, MBOAT7, GCKR and HSD17B13 have also been implicated. NAFLD is a complex disease, and any one genetic variant alone is insufficient for risk stratification, but combining multiple genetic variants with other parameters is a promising strategy. Summary It is anticipated that, in the near future, analysis of data from large-scale prospective cohorts will reveal NAFLD subtypes and enable the development of prognostic models. This will facilitate risk stratification of patients, enabling optimisation of resources to effectively manage the NAFLD epidemic.

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