This study tells us that some gluten peptides may be able to reach extra-intestinal organs such as visceral fat tissue, although most of the gluten was not absorbed and passed into the colon. The finding of gluten peptides in circulation, the liver, and visceral fat tissue was associated with changes in gene expression that may have promoted fat gain, at least among mice consuming a 4.5% gluten diet. However, more research is needed to identify the precise mechanism of weight gain and changes in gene expression, as it is possible these effects were secondary to immunomodulation rather than direct action of gluten peptides. These findings confirm and extend those of previous research by the same authors.
Unfortunately, the lack of supporting evidence makes it difficult to be confident in the practical relevance of these findings, especially in light of study limitations like the use of mice, the background diet, the dose of gluten, and the timeframe of consumption.
The fact that mice were the study subjects as opposed to humans goes without saying as a study limitation, and further research will be required to see if similar findings are observed in humans. It has been shown that intestinal epithelial cells in tissue samples exposed to gluten exhibit increased intestinal permeability in both patients with celiac disease and healthy controls. This effect is mediated by gluten’s interaction with the protein zonulin that is responsible for regulating the integrity of tight junctions within the intestinal tract. Therefore, it is possible that gluten peptides may appear in circulation in humans after consumption, where it may then travel to extraintestinal tissues and mediate gene expression, as suggested in the current study.
Whether any gene-modifying effects (assuming they occur) would lead to weight gain is controversial. One of the observed changes in gene expression was a down-regulation of UCP-1 in brown fat tissue. Genetically removing UCP-1 has been shown in mice to induce obesity and negate diet-induced thermogenesis, making this a likely candidate to explain the increased fat gain. Although brown fat is found in adult humans, it exists in far lower quantities relative to overall body size than in mice. Accordingly, the degree to which it influences energy balance in humans remains unknown. There are also genetic differences in brown fat gene expression between mice and men, leaving open the possibility that gluten may interact with brown fat differently in humans.
Changes in gene expression were not limited to brown fat, however. Subcutaneous fat showed a reduction in the expression of BMP7, which has been implicated in the creation of brown fat. The process of turning white fat, such as subcutaneous fat, into brown fat is known as “browning” and leads to the creation of “beige” or “brite” (from “brown-in-white”) fat that shows thermogenic activity similar to classical brown fat. Beige fat has been investigated as a potential anti-obesity agent in humans. Accordingly, a reduction in its creation could hypothetically make weight gain easier.
Visceral fat showed disparate reactions to gluten depending on whether the mice were fed a standard diet or a high-fat diet. The standard-fed mice showed increased expression of inflammatory molecules, while the high-fat-fed mice showed reductions in enzymes involved in fat metabolism. The causes of these different responses were not explored in the current study and require further investigation.
The background diet plays a large role in how dietary modifications are handled by the body. Notably, the gluten was contained in each and every food pellet that the mice consumed, meaning they had constant exposure when they ate. How would the results differ if gluten intake was more intermittent? Also, how would the amount of protein, fiber, and other nutrients in the diet influence how gluten affects health? It is well established that fiber promotes a healthy microbiome and strong gut barrier.
How much gluten is required to see a health effect? Gluten consumption at 4.5% of the diet would correspond to an intake of about 60 grams daily, assuming an average intake of three pounds of food by an adult human. Gluten is roughly 80% of the protein in wheat, meaning that someone would need to consume about 75 grams of protein from wheat products daily. This is about 20 slices of whole wheat bread. How a lower and more realistic intake of gluten would affect health is another question that requires further investigation.
Finally, because measurements were made after the intervention, it is unclear whether the changes in gene expression were the cause of the weight gain, or the result of it. The researchers measured bodyweight on a weekly basis, but measured gene expression and respiration only at study start and study end. It would have been more insightful if these latter measurements were made earlier in the study before meaningful differences in weight emerged, to strengthen the evidence suggesting that these changes did indeed cause weight gain, since causes precede effects.
The study under review tells us that mice consuming the equivalent of 20 slices of whole wheat bread daily (in terms of gluten content) had metabolic alterations that promote reduced energy expenditure and increased fat gain, possibly through a direct effect on fat tissue. How this study would play out in humans remains unclear.