MicroRNA-targeted suppression of liver fat - Geula Hanin and Prof. Hermona Soreq

Graphical abstract

Fatty liver is a common disease, affecting 25% of the population, and is characterized by the accumulation of fat in the liver. Fatty liver may develop in people who are overweight or obese, or who have diabetes, high cholesterol, or high triglycerides, or those who inherited mutations in the cholesterol receptor gene. The first stage of the disease, called ‘hepatic steatosis’, can progress to a condition called NASH (non-alcoholic steatohepatitis) and eventually cirrhosis or liver cancer. Currently, there are no effective treatments for fatty liver disease. New research performed by Geula Hanin and colleagues from the laboratory of Prof. Hermona Soreq at the Life Sciences Institute, leans on molecular biology tools for identifying a novel cause for fatty liver disease.
The researchers studied a small gene product, called micoRNA which can "silence" or "turn off" genes – and may send brain-to-body commands for changing metabolism. They discovered that one particular microRNA, known as miRNA-132, accumulates both in brain neurons under acute stress and in fatty livers of fattened mice consuming a high-fat diet, a treatment which mimics the most common cause of the disease; and in human patients with fatty liver disease. Furthermore, injecting an ‘antisense’ oligonucleotide inverse to miRNA-132 to fattened mice reversed the fatty liver and hyperlipidemia states, retrieving normal lipid levels in the blood and in the liver; whereas engineering a mouse with inherited high levels of miRNA-132 led to fatty liver and high blood lipids.
So, does psychological stress induce fatty liver disease? This awaits further research; meanwhile, small DNA-based molecules are already used elsewhere to silence miRNAs, for example- to lower blood cholesterol to normal levels. This new molecular biology-based approach may soon become the next trend in precision medicine, solving challenging problems via exploiting the power of molecular biology


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