Exploring the Impact of Wheat Gluten on Body Mass Regulation and Neuroinflammation in Mice


In recent years, the role of diet in influencing obesity and associated metabolic disorders has gained significant attention. A particularly controversial component under investigation is gluten, a protein commonly found in wheat and related grains.

While gluten sensitivity and celiac disease are well-known conditions triggered by gluten consumption, research is uncovering potential broader effects of gluten consumption on body mass regulation and neuroinflammation. In this study, the impact of wheat gluten consumption on body mass, adipose tissue distribution, and hypothalamic neuroinflammation in mice was explored.


Male C57BL/6 mice were used as an animal model to assess the effects of wheat gluten consumption. The study involved the feeding of high-fat diets (HFD) and low-fat diets (LFD) with or without the addition of wheat gluten. Body mass, adipose tissue mass, food intake, energy expenditure, oxygen consumption, and respiratory quotient were monitored. Hypothalamic gliosis, marked by astrocyte and microglia activation, was assessed using immunoreactivity techniques.

Leptin levels, a key hormone in regulating energy balance, were also measured. Further investigations were made into the potential mechanisms underlying the observed effects, including a focus on toll-like receptor 4 (TLR4) activation and the presence of amylase trypsin inhibitors (ATIs) in gluten.


The study revealed intriguing findings related to wheat gluten consumption in mice:

  • Contextual Effects on Body Mass Regulation: The addition of 4.5% wheat gluten to HFD led to a moderate increase in body mass, mimicking human average daily consumption. However, this effect was specific to HFD consumption and was not observed in mice fed LFD. The gluten-induced body mass gain was not attributed to altered food intake or energy expenditure.
  • Adipose Tissue Distribution: The addition of wheat gluten to HFD resulted in an increase in the mass of inguinal and retroperitoneal white adipose tissue (WAT) depots. Notably, this study suggested that gluten specifically increased the mass of certain visceral fat depots, which could have implications for metabolic syndrome risk.
  • Neuroinflammation in the Hypothalamus: Gluten consumption was associated with marked astro- and microgliosis in the hypothalamic arcuate nucleus (ARC) in both LFD and HFD contexts. These changes occurred independently of body mass gain, suggesting a direct immunomodulatory effect of gluten. The presence of gliosis in the hypothalamus is significant due to its role in metabolic regulation.
  • Potential Mechanisms: While the exact mechanisms are still to be determined, the study suggested that amylase trypsin inhibitors (ATIs) present in wheat gluten could be involved in triggering astro- and microgliosis through toll-like receptor 4 (TLR4) activation. This inflammatory response could be tied to changes in the gut microbiome and barrier function.


This study sheds light on the complex effects of wheat gluten consumption in mice. While gluten’s obesogenic effects were evident in the context of a high-fat diet, its impact on hypothalamic neuroinflammation was more pronounced and independent of body mass gain. The study highlights the potential involvement of ATIs and TLR4 activation in triggering astro- and microgliosis. These findings underscore the need for further investigation into the impact of gluten on human health, particularly in the context of gluten sensitivity and metabolic disorders.


The research provides valuable insights into the diverse effects of wheat gluten consumption on body mass regulation and neuroinflammation. The study highlights the context-dependent impact of gluten on body mass, adipose tissue distribution, and hypothalamic gliosis in male mice. The potential involvement of ATIs and TLR4 activation adds a new layer of complexity to our understanding of gluten’s effects on health. Further studies are essential to determine whether these findings are translatable to humans and to explore the broader implications for metabolic health and disorders associated with gluten consumption.


Please enter your comment!
Please enter your name here

Questo sito usa Akismet per ridurre lo spam. Scopri come i tuoi dati vengono elaborati.