Dr Alex Tups, is a neuroendocrinologist investigating how our bodies control our weight. “We investigate the neuroendocrine regulation of body weight,” Alex says, “our main focus at the moment is to understand how the brain controls glucose homeostasis.” He and his team have approached this question by focusing on the relationship between two hormones; leptin and insulin. Insulin may sound familiar to you, as it's often spoken about with regards to diabetes. Under normal conditions insulin acts to facilitate glucose uptake by the body's cells, and leptin signals for us to stop eating. “If you don't have insulin you're diabetic,” Alex says, “and if you don't have leptin you become obese and diabetic.” These hormones share pathology, and they both act within the brain, so by understanding them Alex and his team could start to understand how our body weight is regulated.
“In obesity you have too much of both leptin and insulin, you become resistant to both of them in the brain,” Alex says, “if we can overcome that mechanism then we can treat obesity and we can treat diabetes.” The road to understanding these hormones is a long and difficult one, but Alex and his team are pulling apart the puzzle piece by piece. In examining leptin resistance the team are attempting to isolate the effect of high levels of leptin from the environmental effects that cause it. “A high fat diet produces too much leptin, which could be causing the resistance,” Alex says, “or it could be the diet itself, because a high fat diet causes inflammation in the brain and that inflammation could create the resistance.” Understanding the effect of these hormones is made all the more difficult by the undeniable impact of the environment on body weight. The team are also investigating time of feeding as a potential cause of insulin resistance and weight gain. Teasing out the difference between neuroendocrine effects and environmental effects now could mean a world of difference for treatments down the line, and so Alex and his team are doing what they can to understand these interactions.
The other half of Alex's work focuses in Alzheimer's disease. “Alzheimer's disease has been termed by some researchers as 'type 3 diabetes',” Alex says, “due to the overlap between diabetes and Alzheimer's, and because of the effect of insulin on cognitive function.” While examining the relationship between Alzheimer's disease and diabetes Alex and his team discovered the Wnt pathway. “The Wnt pathway is how the brain regulates glucose homeostasis,” Alex says, “it's involved in the development of Alzheimer's disease, plaques and tangles are all caused by abnormal functioning in this pathway.” What Alex found was that if this pathway was blocked in the brain then diabetes would develop, while Alzheimer's research has shown that the same action also causes Alzheimer's disease to develop. When they examined the pathway in mice Alex and his team found that if they suppressed the pathway they would trigger diabetes, while if they stimulated the pathway they could reverse the pathology.
Trying to understand the brain is never a simple prospect, and Alex's work is a great example of that. In order to understand how a biological system works it has to be taken apart, and the effect of the environment taken into account. In trying to understand glucose homeostasis Alex and his team have found that some of the greatest health concerns in our society, obesity and Alzheimer's disease, could be linked. The work is far from over, but the more we know about these systems and how they interact, the better equipped we will be for the future.