Exosome messages from fat cells to prevent diabetes

Exosome messages from fat cells to prevent diabetes


Losing weight appears to reset the chemical messages that fat cells send to other parts of the body that otherwise would encourage the development of Type 2 diabetes, substantially reducing the risk of that disease, a researcher team report in a new study.

Previously researchers showed that fat cells (also known as adipocytes) from people who are obese send messages to other cells that worsen metabolic function. These messages are in the form of exosomes, nanosized blobs whose contents regulate which proteins are produced by genes.

The messages contained in exosomes from patients who are obese alter how the body processes insulin, setting the stage for Type 2 diabetes. However, it has remained unclear since that publication whether these aberrant messages from adipocytes improve after weight loss.

To investigate this question, researchers worked with six African American adults scheduled to receive gastric bypass surgery -- a nearly surefire way to quickly lose a large amount of weight. The volunteers, whose average age was 38 years, started out with an average body mass index (BMI) of 51.2 kg/m2. (The Centers for Disease Control and Prevention considers a healthy BMI to range between 18.5 to 24.9.)

Two weeks before these volunteers underwent surgery, researchers collected blood samples and took a variety of measurements. The researchers then performed a repeat blood draw and measurements one year after the surgery took place, when the volunteers' average BMI had dropped to 32.6.

Researchers drew out the adipocyte-derived exosomes from both sets of blood samples and analyzed their contents. The team reports in the journal Obesity that at least 168 microRNAs -- the molecules responsible for sending specific messages -- had changed before and after surgery. Further analyses showed that many of these microRNAs were involved in insulin signaling, the pathways that the body uses to regulate blood sugar. By changing these outgoing microRNAs for the better, senior author says, adipocytes actively were encouraging higher insulin sensitivity in other cells, warding off Type 2 diabetes.

Sure enough, each volunteer had better insulin sensitivity and other improved markers of metabolic health post-surgery, including lower branched chain amino acids and a two-fold reduction in their glutamate to glutamine ratio.

The authors plan to study this phenomenon in other types of weight loss, including the slower and steadier paths that most individuals take, such as improving diet and doing more exercise. The team expects to see similar changes in exosomes of patients who lose weight in non-surgical ways.

http://onlinelibrary.wiley.com/doi/10.1002/oby.21709/abstract;jsessionid=45087AB0CA7A05EAE87E55416DBAE98A.f03t01

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