Study Ties Body Mass Index To Size Of The Hypothalamus

By Deborah Borfitz 

September 20, 2023 | The brain structure of people with higher body mass index (BMI) looks quite different than individuals of a healthy weight, based on MRI scans of their hypothalamus analyzed with a recently developed machine learning algorithm. “We specifically wanted to look at the hypothalamus because it’s a small region of the brain that we know plays a really important role in appetite and hunger,” according to Stephanie Brown, Ph.D., principal investigator and senior research associate at the University of Cambridge (U.K.). 

Much of what has been learned to date about the tiny, almond-sized structure has been gleaned from studies in mice because the region is hard to make out on traditional brain scans, she says. Here, Brown and her colleagues applied a novel automated segmentation algorithm to investigate the relationship between hypothalamic volume and body mass index across four independent datasets where brain scans were taken on young adults spanning a range of BMI scores.   

Their study compared underweight, healthy weight, overweight, and obese individuals in a series of complementary analyses. As reported in NeuroImage: Clinical (DOI: 10.1016/j.nicl.2023.103478), the hypothalamus was substantially larger in the overweight and obese groups. The volume of the hypothalamus and BMI were also significantly related.  

Importantly, the volume differences were most apparent in sub-regions of the hypothalamus that control appetite through the release and receipt of hormones, Brown says. The driving subregions seem to be the mediobasal hypothalamus containing the arcuate nucleus comprising specialist neuronal populations for controlling hunger and satiety. 

The algorithm was created by Billot et al. in 2020 (NeuroImage, DOI: 10.1016/j.neuroimage.2020.117287) using convolutional neural networks, allowing for high-accuracy size measurements without the need for a human radiologist—and, as a matter of practicality, making large-scale studies of the hypothalamic structure in humans feasible to conduct. Brown says the research team is interested in expanding their research to see if the positive relationship between hypothalamic volume and BMI is consistent with hypothalamic inflammation that develops rather quickly in animals placed on a fat-rich diet. 

Cause or Effect? 

One hypothesis is that hypothalamic inflammation requires the animals to eat more to feel full. “If what we see in mice is the case in people, then eating a high-fat diet could trigger inflammation of our appetite control center,” says Brown. “Over time, this would change our ability to tell when we’ve eaten enough and to how our body processes blood sugar, leading us to put on weight.” 

It could be that the human body reacts to inflammation by increasing the size of the brain’s specialist immune cells (i.e., microglia), Brown says. While the researchers wouldn’t necessarily expect to see structural changes in the brain of human subjects over the short term, she adds, over longer periods they might be able to tease out the effects of dieting and exercise on the size of a person’s hypothalamus.  

It remains to be proven that the structural changes witnessed in the hypothalamus are caused by being overweight rather than a consequence of the changes in volume, predisposing people to eat too much, Brown notes.  

“Small is not necessarily better” when it comes to the hypothalamus, she says. Patients with the genetic neurodevelopmental disorder known as Prader–Willi syndrome, for example, have lower hypothalamic volume and yet tend to have quite severe hyperphagia and thus have feelings of extreme, insatiable hunger that can make it difficult for them to know when they are full. It is likely in the case of Prader-Willi syndrome that the hypothalamus develops differently from a very young age, adds Brown. 

The long-term goal here is to generate a more comprehensive understanding of obesity to help control the waistlines of the more than 1.9 billion people worldwide who are either overweight or obese. “We know that obesity has a myriad of significant negative health effects, including increasing the risk of type 2 diabetes, heart disease, stroke, and poor mental health,” Brown says.  

Beyond the hypothalamus, other factors known to influence the type and quantity of food people consume include their genetics, hormone regulation, and their lived-in environment.