Researchers at the Max Delbruck Center for Molecular Medicine (MDC) have found that a protein key to the balance of metabolic processes can make fat cells overly sensitive to insulin and lead them to break down less fat.
The study findings, published in The Journal of Clinical Investigatio, showed that SORLA, a protein previously known for its protective role in Alzheimers disease, may disrupt fat metabolism in adipose tissue, a particular form of fat releasing important hormones vital to the body.
SORLA works by sorting proteins to processing where they are either broken down or headed for recycling, which is a good thing in Alzheimer’s as it reduces levels of proteins that form dangerous deposits.
When upregulated in the fat cells of adipose tissue, however, SORLA causes these fat cells to become overly sensitive to insulin, which in turn actively encourage excessive build-up of fat.
The author of the study, Thomas Willnow, and his colleagues have teamed up with researchers from the German Institute of Human Nutrition, the University of Leipzig and Umeå University in Sweden to determine details of SORLA’s metabolic function.
The consortium of scientists has conducted various huma, mice and cell cultures studies describing mechanisms governing the regulation of SORLA in fat cells.
When they analysed the adipose tissue of 362 overweight people, the researchers found that as levels of SORLA rise, their body fat increased exponentially.
The research scientists were also able to establish a link between certain hereditary forms of the SORLA gene and the body fat composition of mice.
The results suggest, however, how appropriate nutrition can help modulate the expression of the defective SORLA gene producing high levels of the protein.
Mice with too much SORLA eating a diet high in fat and carbohydrates quickly gained extreme amounts of weight. But when the animals ate normal food, their weight didn’t change much whether they had normal, excessive, or low levels of SORLA to begin with.
The researchers noticed as well in cell cultures how cells with an excess of SORLA clearly reacted more strongly to insulin. SORLA wrongly recycles molecular receptors for insulin destined to be broken down in compartments called lysosomes.
With higher levels of SORLA, more insulin receptors reach the surface of the cell and, as a result, more insulin molecules can bind to the cell, making it oversensitive to the hormone and breaking down less fat than it should.
Taken together, findings from this cohort of studies on SORLA document an entirely new insulin signalling pathway and indicate that adipose tissue overly sensitive to insulin only becomes a problem if exacerbated by an unhealthy diet.

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