Consumption of gluten harms the hypothalamus region of the brain in male mice and may lead to obesity, study finds

A recent study from New Zealand found that adding gluten to the diets of male mice already consuming a high-fat regimen resulted in an increased body weight and fat content. This addition of gluten also elevated inflammation markers and prompted a growth in astroglia and microglia cells within the hypothalamus of the mice’s brains. This study appeared in the Journal of Neuroendocrinology.

Gluten is a protein complex present in grains like wheat, rye, barley, and oats, accounting for approximately 75% of the total protein in wheat. It’s essential for providing dough its structure and elasticity, which is why it’s favored in baking, giving bread and similar products their characteristic texture. Nonetheless, there have been links between gluten consumption and various health issues, including celiac disease, non-celiac gluten sensitivity, dermatitis herpetiformis, gluten ataxia, and wheat allergy.

About 5% of the global population is believed to be affected by gluten-related diseases. Historically, these conditions were primarily diagnosed in people of European origin. However, with the increased consumption of wheat-based foods globally, medical professionals began diagnosing gluten-related disorders in Asian and other populations. Despite their rarity, especially the severe ones, gluten-free diets have gained immense popularity. For instance, in 2015, a quarter of Americans claimed to consume specific gluten-free products.

Study author Mohammed Z. Rizwan and his colleagues wanted to explore whether adding gluten to the diet of mice would lead to adverse health effects such as altered body mass, changes in metabolic markers, or inflammation levels. Although mice also have their food preferences, they would likely not avoid gluten like many modern humans tend to.

For the study, 10-week-old male mice were sourced from the University of Otago’s animal breeding facility. They were housed in open-top cages, exposed to alternating 12-hour light and dark cycles.

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The mice were separated into two main groups based on diet: one consumed a low-fat diet (10% calories from fat) and the other, a high-fat diet (60% calories from fat sourced from lard and soya bean oil). Each primary group was then split again, with one subgroup receiving wheat gluten in their food (4.5% of calories) and the other not. This resulted in four distinct dietary groups, each containing 16 mice matched for age and weight. These diets were maintained for 14.5 weeks.

The research team monitored the mice for changes in body mass, oxygen consumption (a measure of energy expenditure), and drew blood to check leptin (indicative of hunger and fat tissue quantity) and C-reactive protein (CRP, a marker for inflammation) levels. Post the study duration, mice were fasted for 12 hours, anesthetized, and dissected for brain examination, focusing on gliosis or the growth of glial cells. These cells in the central nervous system support and insulate neurons. Their increased presence can signal various adverse processes, including responses to injuries, infections, or neurological disorders.

Results showed that mice fed high-fat diet increased their body mass much more than the low-fat diet group. After 14.5 weeks of study, mice fed low-fat diet gained 2.9 grams on average. This is the regular increase that is expected in mice as they age. In contrast, the high-fat diet group gained 16.5 grams on average.

Mice fed high-fat diet with the addition of gluten gained even more weight, 20.4 grams on average. Adding gluten to the low-fat diet had no effect – there was no difference in weight gained between the low-fat diet with gluten added group and the group of mice that ate a low-fat diet without added gluten. As the researchers expected, mice who were fed high-fat died consumed more calories compared to the group that ate the low-fat diet. Adding gluten to the diet did not affect the daily energy expenditure of mice.

After killing the mice, researchers extracted and weighed their fat depos. They found that mice that were fed high-fat diet added much more fat compared to mice fed the low-fat diet. The increase in weight was mostly due to the accumulation of extra fat in mice who gained more weight.

The results highlighted that mice on a high-fat diet significantly increased their body weight compared to those on a low-fat diet. After 14.5 weeks, the low-fat diet mice gained an average of 2.9 grams, which aligns with typical age-related weight gain. In contrast, the high-fat diet mice gained an average of 16.5 grams.

Introducing gluten to the high-fat diet further increased weight gain to an average of 20.4 grams. However, adding gluten to the low-fat diet didn’t impact weight gain. As anticipated, high-fat diet mice consumed more calories than their low-fat diet counterparts, but gluten intake didn’t alter daily energy expenditure.

The researchers also found that the high-fat diet increased leptin levels in the blood, an effect not influenced by gluten. But mice consuming gluten exhibited raised CRP levels, indicating inflammation.

Interestingly, the high-fat diet alone elevated the count of astrocytes (a glial cell type) in the arcuate nucleus of the hypothalamus. Gluten, on the other hand, increased both astrocyte and microglia counts irrespective of the fat content in the diet.

“The brain has two types of immune cells similar to macrophages in the blood,” explained study author Alexander Tups in a news release. “These are called astrocytes and microglia. We found that gluten as well as high-fat diet increases the number of those immune cells. The effect of gluten added to normal diet increased the cell number to the same extent as if mice were fed an high-fat diet. When gluten was added to the high-fat diet, the cell number went up even further.”

The hypothalamus is a small but essential region of the brain that plays a crucial role in many vital functions, especially in maintaining homeostasis, which is the body’s ability to maintain a stable internal environment despite external changes.

“If gluten led to hypothalamic inflammation in humans and therefore brain damage, it can be bad in the long run, such as increase in body weight and impaired blood sugar regulation,” Tups said. “If these effects became persistent they might exacerbate the risk of e.g. impaired memory function which is linked to disturbed blood sugar regulation.”

The study makes a valuable contribution to the scientific understanding of the effects of gluten consumption on mammal organisms. However, it should be emphasized that the study was done on mice. Although physiologies of mice and humans share many similarities, they are not identical, nor are diets of mice and humans. Effects of a similar treatment on humans might not produce equal results.

“We are not saying that gluten is bad for everyone,” Tups added. “For gluten tolerant people to go entirely gluten free may have health implications that may outweigh potential benefits. Often people don’t consume wholefoods and highly processed gluten free products are often low in fibre and high in sugar.”

“We are saying that future studies need to reveal whether our findings in mice are translatable to humans and whether gluten-induced astro- and microgliosis may also develop in gluten sensitive individuals.”

The study, “Dietary wheat gluten induces astro- and microgliosis in the hypothalamus of male mice”, was authored by Mohammed Z. Rizwan, Romy Kerbus, Kaj Kamstra, Pramuk Keerthisinghe, and Alexander Tups.