Scientists Discover Gene Required for Lipogenesis

Researchers at the University of California in Berkeley have identified a gene that helps our body convert dietary carbohydrates into fat. The discovery could provide a new target for potential treatments for fatty liver disease, diabetes and obesity.

This micrograph shows marked steatosis in non-alcoholic fatty liver disease (Nephron / CC BY-SA 3.0)

According to epidemiological studies, more than three-quarters of obese people and one-third of Americans have fatty liver disease (steatosis). A diet excessively high in bread, pasta, rice, soda and other carbohydrates is a major risk factor for fatty liver, which is marked by the abnormal accumulation of fat within a liver cell.

After a meal, carbohydrates are broken down into glucose, an immediate source of energy. Excess glucose gets stored in the liver as glycogen or, with the help of insulin, converted into fatty acids, circulated to other parts of the body and stored as fat in adipose tissue. When there is an overabundance of fatty acids, fat also builds up in the liver.

“Fatty liver caused by the high intake of carbohydrates can be as bad as that due to excessive alcohol intake, and it contributes to various diseases including type 2 diabetes. The conversion of excess glucose into fatty acids occurs in the liver, but there are many steps in this process that have not been fully understood,” said Prof Hei Sook Sul, senior author on the study published in the journal Molecular Cell.

The researchers discovered that a gene called the Brg1/Brm-associated factor 60c (BAF60c for short), also known as SMARCD3 gene, plays a critical role in the conversion of dietary carbohydrates to fat.

They found that BAF60c resides in the cytoplasm, outside the cell’s nucleus. Once insulin binds to a receptor on the cell surface, it sends a signal to modify BAF60c so that it enters the nucleus. There, BAF60c binds to regions of chromatin that contain genes coding for various enzymes involved in the conversion of carbohydrates to fat. This action sends the signal to churn out more of the enzymes, enhancing the conversion of carbohydrates to fat.

They tested the role of BAF60c by both increasing and decreasing its function in various experiments in live mice. Mice that had triple the normal levels of BAF60c in their livers produced significantly higher levels of fat-producing genes, even when they were fasting. In contrast, disabling BAF60c disrupted the formation of fatty acids, even when the mice feasted on a carbohydrate-heavy diet.

The scientists point out that fatty liver disease can result from overindulging in carbohydrates. They suggest avoiding refined sugars that increase blood insulin levels quickly, but note that there are complex carbohydrates – such as those in legumes, fruits and vegetables – that should be part of a healthy diet.

“Limiting consumption of sodas, cakes and cookies is a good idea for many reasons, even during the holidays,” Prof Sul concluded.

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Bibliographic information: Yuhui Wang et al. Phosphorylation and Recruitment of BAF60c in Chromatin Remodeling for Lipogenesis in Response to Insulin. Molecular Cell, published online 06 December, 2012; doi: 10.1016/j.molcel.2012.10.028