BY: Andrew Hardaway, PhD

DATE: May 28, 2016

There is a growing interest in studying how our diet impacts brain health and function. In a recent paper¹, a group of German scientists made a novel discovery about how the consumption of high fat foods impacts brain health function. People and rodents primarily use the carbohydrate glucose to provide energy to the body’s cells and have evolved complex biological mechanisms to ensure its distribution to even its most remote, seemingly innaccesible tissues. Measurements of glucose uptake, the process of moving glucose from the blood stream to the body’s cells, in humans or animals are made possible through advanced imaging techniques like positron emission tomography (PET) in combination with a glucose analog called ¹⁸F-FDG. Previous studies using PET clearly demonstrate that the brain is the most glucose-rich organ in the body. The brain is made up of a highly dense network of neurons and glia that constantly engage in energy-intensive processes and its glucose supply is tightly controlled through a separate network of blood vessels. Although the study of glucose dynamics in the blood has been well studied with regards to chronic high fat diets and type II diabetes, the regulation of glucose uptake and use in the brain in response to high fat diet was still unknown.

The authors used a simple model of high fat diet access over multiple days and used ¹⁸F-FDG PET imaging in live mice and observed reductions in glucose uptake in several key brain regions like the motor cortex, somatosensory cortex, hypothalamus, and nucleus accumbens relative to a pre-high fat diet baseline period. This surprising result clearly demonstrates that despite an increase in energy intake in the form of mostly dietary fat, the brain is actually being deprived of its primary energy source in these important brain regions.

The question that the authors pursued next was “How is high fat diet producing these deficits in glucose uptake in the brain?” Glucose uptake occurs in blood endothelial cells through a protein known as the glucose transporter that transports glucose from circulating blood and provides it to nearby cells. The glucose transporter acts like a vacuum specifically for glucose, leaving other blood molecules untouched. The authors observed that short-term high fat diet access reduces the presence of glucose transporter in the brain, whereas long-term access to high fat diet had normal glucose transporter function. They then showed that glucose transporter function in blood endothelial cells (blood vessels) was essential for life and brain glucose uptake. Next, in a series of elegant experiments, the authors showed that the brain compensates for this short-term decrease in glucose transporter expression and function by the induction of a well-known signaling pathway called vascular endothelial growth factor (VEGF). VEGF is expressed in a subset of the body’s immune cells called macrophages, and the induction of VEGF signaling in macrophages sets in place a cascade of events that increases glucose tranporter function and elevates glucose uptake in the brain. They showed that mice bearing a loss of VEGF in a macrophage-lineage cell type were unable to compensate to high fat diet induced changes in brain glucose uptake, blood glucose intolerance, inflammation, and had cognitive-like impairments. These experiments showed that our brains have evolved several key molecules that help distribute glucose to the brain and that their function are impaired following consumption of high fat diet, but the brain can eventually compensate to restore glucose supply.

These studies provide a novel view of the mechanisms by which the brain and its associated blood vasculature are working to feed itself and how these systems interact with our diet. Future studies examining the behavioral impact of the high fat diet-induced disruptions in glucose uptake in specific brain regions may provide a novel window in understanding how diets rich in fat shape brain function and behavior. Furthermore, these studies show that targeting the glucose transporter and VEGF might be an effective treatment for individuals suffering from cognitive decline.

¹Article Info:

1. Jais, A. et al. Myeloid-Cell-Derived VEGF Maintains Brain Glucose Uptake and Limits Cognitive Impairment in Obesity. Cell 165, 882–895 (2016).