A recent study conducted on mice sheds light on the complex interplay between wheat gluten consumption, body mass regulation, and neuroinflammation, offering new insights into the potential consequences of gluten consumption in various dietary contexts.
The findings reveal intriguing relationships between wheat gluten consumption, body mass changes, and neuroinflammation in the hypothalamic arcuate nucleus (ARC) of the mice.
Body Mass and Dietary Context
The study demonstrated that the addition of wheat gluten to a high-fat diet (HFD) led to a moderate increase in body mass in mice.
Remarkably, this effect was observed exclusively in the context of the high-fat diet, and not when wheat gluten was added to a low-fat diet (LFD). This suggests a specific interaction between wheat gluten and the dietary fat content, possibly related to the inflammatory response triggered by the combination of gluten and high levels of dietary fat.
Furthermore, the increase in body mass associated with the consumption of wheat gluten in the HFD group was linked to the enlargement of specific adipose tissue depots, including the inguinal and retroperitoneal white adipose tissue (WAT) masses.
This is consistent with previous research that highlights the obesogenic potential of a diet containing gluten. Interestingly, these effects were observed after varying durations of exposure to the gluten-containing diet, indicating the importance of considering exposure time in assessing the impact of gluten consumption on body mass regulation.
Neuroinflammation in the Hypothalamic ARC
A crucial aspect of this study is its exploration of the effects of wheat gluten consumption on neuroinflammation in the hypothalamic ARC, an area of the brain involved in the regulation of appetite and metabolism. The researchers found an increase in the number of astroglial (GFAP) and microglial (Iba-1) cells in the ARC following high-fat feeding. Astroglial activation and microgliosis are indicative of neuroinflammation, and their presence underscores the proinflammatory nature of the high-fat diet used in the study.
Moreover, the addition of wheat gluten, both to LFD and HFD, exacerbated astro- and microgliosis in the ARC. This effect was particularly pronounced when wheat gluten was combined with the LFD, demonstrating that the impact of gluten on neuroinflammation is not limited to high-fat contexts. These findings provide crucial evidence of a direct relationship between wheat gluten consumption and the activation of neuroinflammatory responses.
Mechanisms of Action
The mechanisms underlying the observed effects are complex and multifaceted. The study suggests that the gliadin protein and peptides, prominent components of wheat gluten, could trigger innate immune responses in the gut. This immune response may subsequently lead to hypothalamic inflammation and gliosis either directly through the gut-brain axis or indirectly via alterations in the gut microbiome. The structural similarities between gluten pathogenic peptides and bacterial-derived proteins further support the idea of microbial involvement in the observed neuroinflammatory response.
Implications for Human Health
While the study was conducted on male mice, it raises critical questions about the potential implications of gluten consumption for human health. The findings suggest that gluten-induced neuroinflammation could play a role in the development of metabolic diseases, even independent of its obesogenic effects. This emphasizes the need for further research to determine the relevance of these findings in humans, particularly in individuals with gluten sensitivity.
Conclusion
In conclusion, the study offers valuable insights into the intricate relationships between wheat gluten consumption, body mass regulation, and neuroinflammation. The specific effects of gluten on body mass in the context of high-fat diets and its direct impact on neuroinflammation in the hypothalamic ARC are significant findings that warrant further investigation. As researchers delve deeper into the mechanisms at play, these insights could contribute to our understanding of the potential health consequences of gluten consumption and its role in metabolic disorders.
In deep:
Astroglial activation and microgliosis are two of the main hallmarks of neuroinflammation.
- Astroglial activation is the process by which astrocytes, the supportive cells of the brain, become enlarged and reactive. This can be caused by a variety of factors, including injury, infection, and neurodegenerative diseases. Activated astrocytes release a variety of molecules, including cytokines, chemokines, and growth factors, which can contribute to inflammation and tissue damage.
- Microgliosis is the process by which microglia, the immune cells of the brain, become activated. Microglia are normally in a resting state, but they can become activated in response to injury, infection, and neurodegenerative diseases. Activated microglia release a variety of molecules, including pro-inflammatory cytokines, reactive oxygen species, and free radicals, which can damage neurons and contribute to neurodegeneration.
The activation of astroglia and microglia is a complex process that is not fully understood. However, it is clear that these cells play a key role in neuroinflammation and neurodegenerative diseases.
Here are some of the neurodegenerative diseases that are associated with neuroinflammation:
- Alzheimer’s disease
- Parkinson’s disease
- Multiple sclerosis
- Amyotrophic lateral sclerosis (ALS)
- Huntington’s disease
- Traumatic brain injury
- Stroke
Why are astroglial activation and microgliosis indicative of neuroinflammation?
Astroglial activation and microgliosis are indicative of neuroinflammation because they are both associated with the release of pro-inflammatory molecules.
- Astroglial activation is associated with the release of cytokines, chemokines, and growth factors. These molecules can attract and activate microglia, as well as other immune cells. They can also cause damage to neurons and promote neurodegeneration.
- Microgliosis is associated with the release of pro-inflammatory cytokines, reactive oxygen species, and free radicals. These molecules can also damage neurons and promote neurodegeneration.
In addition, astroglial activation and microgliosis can both lead to the formation of reactive gliosis, which is a scar-like tissue that can further damage neurons and impair brain function.
Therefore, the activation of astroglia and microglia is a hallmark of neuroinflammation and is a major contributor to the damage that occurs in neurodegenerative diseases.
Here are some of the pro-inflammatory molecules that are released by activated astroglia and microglia:
- Cytokines: Cytokines are signaling molecules that regulate the immune response. Some of the pro-inflammatory cytokines that are released by activated astroglia and microglia include interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ).
- Chemokines: Chemokines are signaling molecules that attract immune cells to the site of inflammation. Some of the chemokines that are released by activated astroglia and microglia include CCL2, CCL5, and CXCL1.
- Growth factors: Growth factors are signaling molecules that promote cell growth and repair. However, some growth factors, such as transforming growth factor-β (TGF-β), can also promote inflammation.
The release of these pro-inflammatory molecules can lead to a number of harmful effects, including:
- Neuronal damage: Pro-inflammatory molecules can damage neurons by causing oxidative stress, apoptosis, and necrosis.
- Glial scarring: Pro-inflammatory molecules can promote the formation of reactive gliosis, which is a scar-like tissue that can further damage neurons and impair brain function.
- Immune cell recruitment: Pro-inflammatory molecules can attract and activate immune cells, such as T cells and B cells. These cells can also release pro-inflammatory molecules, which can further contribute to the damage that occurs in neuroinflammation.
Therefore, the activation of astroglia and microglia is a major contributor to the damage that occurs in neurodegenerative diseases. By understanding the mechanisms by which astroglial activation and microgliosis occur, researchers may be able to develop new treatments that target this process and slow the progression of these diseases.
reference link : https://onlinelibrary.wiley.com/doi/10.1111/jne.13326
