Genetic Link Confirmed for Neurodegeneration and Metabolism

Alan R. Jacobs, MD


August 18, 2016

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This is the Medscape Neurology Minute. I'm Dr Alan Jacobs.

Researchers from the Max Delbrück Center for Molecular Medicine in Berlin, Germany, have published a study detailing the metabolic function of the intracellular sorting receptor SORLA, a known genetic risk factor for Alzheimer's disease, in a new role regulating metabolism in human obesity.[1]

In 362 overweight people, they observed gene-dosage effects that link SORLA expression to obesity and glucose tolerance. Higher amount of SORLA in adipose tissue was associated with increased weight.

In mice, overexpression of human SORLA in murine adipose tissue blocked hydrolysis of triacylglycerides and caused excessive adiposity. Sorl1 gene knockout in mice accelerated the breakdown of triacylglycerides in adipocytes and protected the animals from diet-induced obesity.

Finally, the researchers determined that in cultured adipose cells, SORLA acts as a sorting factor for the insulin receptor that redirects internalized receptor molecules from endosomes to the cell surface membrane. This enhances insulin receptor surface expression and strengthens insulin signal reception in the cells.

The authors concluded that Sorl1 is associated with human obesity, and their findings confirm a genetic link between neurodegeneration and metabolism that converges on SORLA.

This has been the Medscape Neurology Minute. I'm Dr Alan Jacobs.


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