Sugar rush shrinks brain cell powerhouse

Sugar rush shrinks brain cell powerhouse

Blood glucose levels are thought to be primarily controlled by the pancreatic hormone insulin, the liver, and the muscles. This new study, however, highlights a crucial role for mitochondria in a small subset of neurons of the brain in systemic glucose control.

The study was designed to explore how neurons in the brain adapt to the glucose "rush." The researchers were surprised to find that not only do mitochondria of neurons "feel" the change in circulating glucose levels, but that adaptive changes in these same mitochondria are at the core of the body's ability to handle sugar in the blood.

To test this point, the research team generated several mouse models in which a specific mitochondrial protein called uncoupling protein 2 (UCP2) was either missing or present in varying amounts in the subset of brain cells that sense circulating sugar levels.

Glucose load results in mitochondrial fission and reduced reactive oxygen species in the ventromedial nucleus of the hypothalamus (VMH) neurons mediated by dynamin-related peptide 1 (DRP1) under the control of uncoupling protein 2 (UCP2). Probed by genetic manipulations and chemical-genetic control of VMH neuronal circuitry, authors unmasked that this mitochondrial adaptation determines the size of the pool of glucose-excited neurons in the VMH and that this process regulates systemic glucose homeostasis. 

"We found that when sugar increases in the body, mitochondria in subsets of brain neurons rapidly change their shape and their function is altered," said senior author.

what surprised the research team is not that these changes occur in response to glucose, but that these seemingly subtle adjustments in a "housekeeping" cellular event in a handful of brain cells has such a powerful impact in circulating glucose levels by affecting many peripheral tissue functions.

"The findings imply that alterations in this mechanism may be crucial for the development of metabolic diseases such as type 2 diabetes, in which the body is not able to clear the blood from high levels of sugar that occur after meals," said another author.