Diabetes and Fatty Liver

by Mark Benson on May 9, 2012

New enzymes to help fight diabetes development

Research headed by Mitchell Lazar MD, PhD, the current director of the Institute for Diabetes, Obesity and Metabolism at the Perelman School of Medicine of the University of Pennsylvania has reported in Nature Medicine the findings that mice with altered histone deactyalase 3 (HDAC 3) protected the animal from glucose intolerance and insulin resistance.

HDAC 3 is a class of enzymes that remove acetyl groups from the acetyl lysine amino acid on a histone. This  is because DNA is wrapped around histones and this is regulated by acetylation and de-acetylation.

When insulin resistance occurs, the body has issues in managing the blood sugar levels in the body. This is often present in individuals with obesity and Type 2 diabetes and another complication would be the observation of having a fatty liver. According to current science, fatty liver contributes to the insulin resistance and exacerbate diabetes in a vicious cyclical nature. This new study shows that the reverse is true.

The study found that the presence of extra fat in the liver did not result in insulin resistance as it was segregated in tiny lipid droplets inside individual liver cells covered with a specific protein. These metabolites that would normally be used by the body to make glucose would be re-done to make fat which leads to the reduction of glucose levels in the bloodstream. The benefits of having lower blood sugar levels would be controlled by the excess liver fat, leading to many problems of its own with the worst being liver failure.

The high fat diet induced fatty liver cells in the mice tested had larger lipid droplets. On the other hand, those with liver specific HDAC3 knocked out in mice with a high fat diet had smaller lipid droplets even if the total lipid content increased compared to the former kind.

This begs the question on the need for this re-routing process in the body. The research team looked for the circadian rhythm in the nocturnal mice to be able to find the justification. The mice are inactive during the day and at this time, the HDAC3 moves to the genes to turn off fat synthesis. When this occurs, the metabolites allow the manufacturing of the glucose to fuel the sleeping individual. When awake at night time, the mouse turns a metabolic switch because of the anticipated intake of food to turn the fat synthesis activity into energy storage. This on and off cycle of HDAC3 is regulated by the body’s biological clock, which in turn falls apart when this enzyme is removed from cells.

These results suggest that by cordoning off lipids of the liver in many individual droplets, insulin resistance is managed in the body. The findings buttress the findings that HDAC3 is important in the integration of signals from the internal body clock to be able to coordinate the metabolic and liver functions.

The findings demonstrate that the fat that is stored is not necessary all bad cholesterol. According to Dr. Lazar, “It matters a lot how fat is handled and stored. It also highlights the importance of complying with our internal circadian clock. For example, since our body does not anticipate food at night and is preparing to generate more glucose, night time eating is likely to shoot up blood sugar and thus may contribute to diabetes.”

The opinions expressed in this article do not necessarily reflect the views of the DiabetesForum.com Community and should not be interpreted as medical advice. Please see your doctor before making any changes to your diabetes management plan.

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