Epigenetics in Obesity and Diabetes Mellitus: New Insights

by Selleckchem | Jun 02 2023

A long-term complication of obesity is the development of type 2 diabetes (T2D). Patients with T2D have been described as having epigenetic modifications. Epigenetics is the post-transcriptional modification of DNA or associated factors containing genetic information. These environmentally-influenced modifications, maintained during cell division, cause stable changes in gene expression. Epigenetic modifications of T2D are DNA methylation, acetylation, ubiquitylation, SUMOylation, and phosphorylation at the lysine residue at the amino terminus of histones, affecting DNA, histones, and non-coding RNA. DNA methylation has been shown in pancreatic islets, adipose tissue, skeletal muscle, and the liver. Furthermore, epigenetic changes have been observed in chronic complications of T2D, such as diabetic nephropathy, diabetic retinopathy, and diabetic neuropathy. Recently, a new drug has been developed which acts on bromodomains and extraterminal (BET) domain proteins, which operate like epigenetic readers and communicate with chromatin to make DNA accessible for transcription by inhibiting them. This drug (apabetalone) is being studied to prevent major adverse cardiovascular events in people with T2D, low HDL cholesterol, chronic kidney failure, and recent coronary events. This review aims to describe the relationship between obesity, long-term complications such as T2D, and epigenetic modifications and their possible treatments.

Comments：

Obesity is a major risk factor for the development of type 2 diabetes (T2D), and it has been shown to cause epigenetic modifications that can lead to stable changes in gene expression. These modifications, which include DNA methylation, acetylation, ubiquitylation, SUMOylation, and phosphorylation at the lysine residue at the amino terminus of histones, affect DNA, histones, and non-coding RNA. The resulting changes in gene expression can contribute to the development and progression of T2D and its chronic complications, such as diabetic nephropathy, retinopathy, and neuropathy.

One potential treatment strategy for T2D and its complications involves targeting the epigenetic modifications that contribute to the disease. Recent research has focused on a new drug called apabetalone, which acts on bromodomains and extraterminal (BET) domain proteins that operate like epigenetic readers and communicate with chromatin to make DNA accessible for transcription by inhibiting them. This drug is being studied to prevent major adverse cardiovascular events in people with T2D, low HDL cholesterol, chronic kidney failure, and recent coronary events.

While the development of apabetalone is promising, it is important to note that obesity and T2D are complex diseases with multiple contributing factors. Lifestyle modifications, such as dietary changes and exercise, are also important for managing and preventing T2D and its complications. Additionally, other potential drug targets, such as enzymes involved in DNA methylation and histone modifications, may also be promising avenues for the development of new treatments.

In summary, epigenetic modifications play a significant role in the development and progression of obesity-related diseases such as T2D. Targeting these modifications with drugs like apabetalone holds promise as a potential treatment strategy for T2D and its complications, but lifestyle modifications and other drug targets should also be considered in the management of these complex diseases.