DGAT2: A promising drug target and biomarker for fatty liver disease

Target Name: DGAT2

NCBI ID: G84649

DGAT2: A promising drug target and biomarker for fatty liver disease

Abstract:

Fatty liver disease (FLD) is a significant public health issue worldwide, affecting millions of individuals and causing significant morbidity and mortality. The development of new diagnostic tools and therapeutic targets for FLD is crucial for improving patient outcomes. One promising candidate for drug targeting and biomarker development is DGAT2, a gene encoding a protein involved in the O-acyl transferase (acyltransferase) pathway in the liver. In this article, we will discuss the potential drug target and biomarker properties of DGAT2, highlighting its unique features and the ongoing research in this field.

1. Introduction

Fatty liver disease (FLD) is a complex condition that characterized by the accumulation of excess fat in the liver, leading to structural changes and functional impairments. It is a major risk factor for various diseases, including liver cirrhosis, nonalcoholic steatohepatitis (NASH), and trans fats clouding obesity (TFL Obes). According to the World Health Organization (WHO), it is estimated that 2.7 billion people worldwide have non-alcoholic fatty liver disease (NAFLD), which represents 85% of all liver diseases.

FLD is a multifactorial disease, and the identification of new diagnostic tools and therapeutic targets is crucial for improving patient outcomes. One promising candidate for drug targeting and biomarker development is DGAT2, a gene encoding a protein involved in the O-acyl transferase (acyltransferase) pathway in the liver.

2. DGAT2: A protein involved in the O-acyl transferase (acyltransferase) pathway

The O-acyl transferase (acyltransferase) is a key enzyme involved in the transfer of omega-3 and omega-6 fatty acids from diet to the membrane of membrane-bound proteins. DGAT2 is a member of the acyltransferase family 2 (ATF2), which includes several other enzymes involved in the transfer of fatty acids, including ATF3, ATF4, and ATF5. DGAT2 is responsible for the transfer of omega-3 fatty acids, primarily EPA and DHA, from the diet to the membrane of membrane-bound proteins , including liver and muscle proteins.

The acyltransferase pathway is a complex process that involves multiple enzymes and substrate. The key step in the pathway is the transfer of an acyl group from the substrate to theacyl transferase enzyme. DGAT2 is one of the enzymes involved in this process, and its activity is regulated by various factors, including diet, genetics, and environmental factors.

3. DGAT2 as a drug target

DGAT2 is a promising drug target for FLD due to its unique features. Firstly, DGAT2 is involved in the transfer of omega-3 fatty acids, which are essential for the structure and function of brain and eye tissues. Secondly, DGAT2 is a fatty acid -binding protein (FABP), which can interact with fatty acids and play a role in the regulation of fatty acid metabolism. This interaction between DGAT2 and fatty acids makes it an attractive target for drugs targeting FLD.

DGAT2 has been the focus of several ongoing clinical trials aimed at developing new treatments for FLD. One of the most promising studies is the ongoing clinical trial using a small molecule inhibitor of DGAT2, which is designed to reduce the amount of omega-3 fatty acids in the liver and improve the liver function in patients with NAFLD.

4. DGAT2 as a biomarker

In addition to its potential as a drug target, DGAT2 is also a promising biomarker for FLD. The accumulation of excess fat in the liver is a key feature of FLD, and DGAT2 has

Protein Name: Diacylglycerol O-acyltransferase 2

Functions: Essential acyltransferase that catalyzes the terminal and only committed step in triacylglycerol synthesis by using diacylglycerol and fatty acyl CoA as substrates. Required for synthesis and storage of intracellular triglycerides (PubMed:27184406). Probably plays a central role in cytosolic lipid accumulation. In liver, is primarily responsible for incorporating endogenously synthesized fatty acids into triglycerides (By similarity). Functions also as an acyl-CoA retinol acyltransferase (ARAT) (By similarity). Also able to use 1-monoalkylglycerol (1-MAkG) as an acyl acceptor for the synthesis of monoalkyl-monoacylglycerol (MAMAG) (PubMed:28420705)

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