Researchers Uncover Potential New Role of Long Noncoding RNA in Fatty Liver Disease


Source: University of Michigan

Summary: Researchers have uncovered a potential new role for long noncoding RNA in obesity and nonalcoholic fatty liver disease.


Nonalcoholic fatty liver disease, an accumulation of too much fat in the liver that affects an estimated 64 million Americans and increases their risk for cirrhosis and liver failure. When mice and humans become obese, the liver increases its conversion of sugar into fat. Previous studies in mice have shown that blocking this conversion pathway can slow down the progression of the fatty liver disease to its more severe and often lethal form, NASH (or nonalcoholic steatohepatitis). Working in mouse models, the researchers identified a specific type of long noncoding RNA (also called lncRNA) that increases fat accumulation in the liver and exacerbates fatty liver disease. In contrast to coding RNA, which use the instructions from DNA to create proteins, lncRNA do not appear to encode any specific proteins. Researchers from the University of Michigan have uncovered a potential new role for long noncoding RNA in obesity and nonalcoholic fatty liver disease. The study findings were published in the journal Nature Communications.

Liver with excess fat

Researchers identify a specific type of long noncoding RNA that increases fat accumulation in the liver and exacerbates fatty liver disease. Credit: Stephanie King, Life Sciences Institute Multimedia Designer

The research team observed increased levels of an lncRNA called Blnc1 (for brown fat lncRNA 1) in liver cells of mice that had been fed a high-fat diet. To investigate the role of Blnc1 in obesity, they used CRISPR gene-editing technology to delete the gene that makes Blnc1 but only from liver cells in the mice, rather than throughout their entire bodies. When fed a high-fat diet, the control mice became obese and developed a fatty liver disease as expected. But the mice without Blnc1 in their livers were protected from high-fat diet-induced metabolic disorders. With this study, the researchers uncovered Blnc1 as a key component of an RNA-protein complex that drives this sugar-to-fat conversion pathway, contributing to obesity, fatty liver disease and NASH.

Prof. Jiandie Lin said, “This is the first knockout animal model study of lncRNA in metabolic regulation and disease” and further added, “Our results offer very compelling evidence that lncRNA itself could be a dominant player in lipid metabolism.”


More Information: Xu-Yun Zhao et al, “Long noncoding RNA licensing of obesity-linked hepatic lipogenesis and NAFLD pathogenesis”, Nature Communications (2018). DOI: 10.1038/s41467-018-05383-2 


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