Athletes and type 2 diabetic patients represent opposite extremes of the insulin sensitivity spectrum. However, both groups have elevated levels of intramyocellular lipid content. This apparent ambiguity, known as the “athlete’s paradox”, has drawn attention to the mechanisms that rule lipid storage, packaging, and degradation.
While most research has been focusing on the protein perilipin 5 in order to gain better understanding of the mechanisms that rule lipid metabolism in skeletal muscle, scientists from Louisiana State University Health Science Center have recently shown the crucial role of another member of the same family, perilipin 3.
In one of their latest projects, the team performed a clinical investigation involving 29 healthy subjects who underwent body composition and metabolic measurements. From MRI scans obtained from the liver to the pubic symphysis, abdominal subcutaneous adipose tissue and visceral adipose tissue volumes were assessed using Analyze software. Volumes were then converted to body-fat percentages.
The investigators found that the content of perilipin 3 was positively associated with the rate of lipid degradation. To further validate their result, they induced lower production of perilipin 3 in skeletal muscle cells and were able to show a significant reduction in fat metabolism.
After highlighting the new potential role that perilipin 3 might play in lipid oxidation, the group focused on differences between perilipin 5 and perilipin 3 protein content in active, lean, and type 2 diabetic individuals. Interestingly, they found that following exercise stimulation active subjects mostly expressed perilipin 5 while the other two cohorts had higher levels of perilipin 3.
These data imply the possible existence of two separate lipid oxidation pathways, dependent on either perilipin 5 or perilipin 3, that are utilized differently in the skeletal muscle of active, lean, and type 2 diabetic subjects. Therefore, the previously unexplored pathway dependent on perilipin 3 may represent a novel, successful pharmacological target for lipid oxidation in diabetic patients.