● Retinoid X receptors (RXRs)
are vitamin A receptors that often partner
with other important receptors,
including retinoic acid receptors, vitamin D receptors, thyroid hormone receptors,
and PPARs.
Therefore, these have critical roles in energy production (obesity, blood sugar, cholesterol), anti-inflammation, preventing leaky gut, skin health, and cancer prevention.
Could low vitamin A or low RXR activation contribute to your health problems?
Read this post to learn more.
● What Is a Retinoid X Receptor?
The retinoid X receptor (RXR) is a vitamin A receptor that often partners with other important receptors inside the cells. As a result, it has several important roles in energy production, immune responses, development and skin health.
● Types of Retinoid X Receptors
There are three main sub-types of retinoid X receptors: RXR-α, RXR-β, and RXR-γ.
RXR-α is found in the liver, lung, muscles, skin, kidney, and intestines
RXR-β is found throughout the body
RXR-γ is found in the brain, heart, and bone muscles [1]
Each RXR subtype is encoded by different genes and interacts with different biological pathways when activated [1].
● Natural Activators of Retinoid X Receptors
9-cis retinoic acid [2]
Honokiol [3]
Green tea increases RXR levels [4]
● 기전 효능
1. 면역
2. 장누수 억제
3.
1) Autoimmunity & Inflammation
Reduces Th1 and Increases Th2 Cells
Th1 and Th2 cell production influences the adaptive immune response. Th1 cells are mostly responsible for protecting against pathogens inside the cells. Meanwhile, Th2 cells protect against parasites that are located outside the cell [6].
The immune response’s outcome is controlled by changing the balance of Th1 and Th2 cells. RXR-α transmission normally suppresses the formation of Th1 cells and indirectly permits Th2 cell formation. Vitamin D receptors work with RXRs to inhibit Th1 and increase the Th2 response [6].
In a study of mice, scientists found that the RXR-α transmission pathway is necessary for Th2 responses. RXR-α deficiency decreases Th2 cell formation and causes Th1 cell levels to be too high [6].
Reduces Th17 and Increase Treg Cells
Th17 cell activation is linked to many autoimmune diseases, while Treg cells reduce autoimmunity. RXRs function with RARs to suppress Th17 cells. Activation of RXRs help inhibit Th17 cell growth and increase Treg cells [7, 8].
This RXR activation in CD4+ T cells (cells that could become either Th17 or Tregs) significantly ameliorated disease severity in mouse models of multiple sclerosis [7].
RXRs increase cAMP production in human skin tissue. This increases the level of immune cells in the skin and increases antimicrobial strength [9].
Helps Prevent Leaky Gut
Leaky gut is a condition where the tight junctions between the cells that line the gut have increased permeability. This means the gut content is exposed to the immune system, potentially causing inflammation [10].
Activation of pathways involving the retinoid x receptors promotes the development of a healthy intestinal barrier, which reduces the risk of a leaky gut [11].
Vitamin A supplementation in healthy children improved gut function, while vitamin A deficiency reduced intestinal barrier function [12].
Supports Healthy Inflammatory Responses
Retinoid X receptors (RXRs) are important for the control of genes that are involved in the immune response to inflammation [5].
In an animal model, mice that lack RXR-α in their myeloid cells had reduced CCL6 and CCL9 (proteins that attract, activate, and induce growth of immune cells) levels. This is evidence that RXR-α is needed for the transcription of these cytokines that respond to inflammation. The lack of RXR-α activation may prevent necessary inflammatory responses in the presence of injuries or infections [5].
RXRs are potential targets for immunotherapy during chronic inflammatory diseases [5].
2) Cancer
Proper retinoid X receptor transmission prevents cancer. The retinoic x receptors have been identified as possible targets for cancer therapy and treatment [13].
In cell studies, RXR-α interacts with other receptors to promote immune transmission that prevents the production of human breast cancer cells [14].
When scientists increased RXR-α in breast cancer cells, the cancer cells became more sensitive to RXR activators. This sensitivity made it easier for the activators to stop the cell growth cycle and stop cell production [14].
Green tea polyphenols activate RXR-α.
Laboratory animals with colon cancer have lower RXR-α production. Increasing RXR levels by green tea polyphenols helped reduce the risk of colon cancer in these animals [4].
DW22, an RXR-α agonist, arrests cell division and kills (induces apoptosis) cancer cells [15].
3) Helps Prevent Obesity
The retinoid X receptors are involved in metabolic transmission pathways that reduce the risk of obesity when properly activated [2].
Laboratory animals without RXR-α in their livers eat less but weigh more compared to healthy animals [2].
RXR-α is found in the liver where it maintains healthy fat metabolism [16].
In one study of diabetic rats, administration RXR activators increased their energy production [2].
On the other hand, the deletion of RXR-α in mice fat cells made them resistant to obesity induced by high-fat diet or chemicals [2].
4) Reduces Cholesterol Levels
Laboratory animals without RXR-α in their livers have higher cholesterol levels and are prone to fatty liver disease [16].
Both of these defects are key risk factors for obesity [16].
Retinoic X receptors also signal with the farnesoid X receptor to balance cholesterol levels in the body [1].
5) Decreases Insulin Resistance
New therapies that improve insulin sensitivity include molecules that partner with RXR as part of a complex with other receptors. These partners then increase the function of genes involved in insulin action, fat cell production, fat energy production, and inflammation [17].
For example, RXR partners with PPARγ. This improves blood glucose levels, blood fat levels, reduces insulin resistance, and prevents other heart disease risk factors [17].
Additionally, treatment of obese and diabetic mice by activating RXR helped improve glucose energy production [18].
RXRγ overproduction in mice resulted in activated glucose energy production genes [18].
In cell-based studies, molecules that activated retinoid X receptors also prevented oxidative damage from high blood sugar [19].
6) Helps Cardiovascular Health
Specific activators that increase RXR activity help prevent vascular diseases (diseases of blood vessel health, such as thrombosis, heart disease, hardening of the arteries) by promoting blood vessel health [20].
Angiotensin II transmission increases inflammatory cytokines and causes abnormal blood vessel growth. In rat cells, RXR reduces angiotensin II signaling [20].
By preventing inflammation in muscle cells, RXR activators prevent blood vessel disorders [20].
7) Helps Maintain Healthy Skin
Retinoid X Receptors are partly responsible for skin vitality and health. In skin cells, RXRs work with the vitamin D receptors to allow for vitamin D synthesis from the sun [21].
These receptors play a crucial part in decreasing the symptoms of chronic hand eczema through increasing vitamin A binding affinity [22].
Additionally, RXRs increase cAMP production in human skin tissue. This increases the immune cells in the skin and increases antimicrobial strength [9].
8) Fetal Development
Healthy retinoic X function in pregnant women promotes proper absorption of vitamin D. This allows normal immune cell production in the placenta and prevents the development of allergies or asthma in newborns [23].
RXR-α is especially important in promoting gene production associated with early-life development; additionally, a fetus cannot develop properly without sufficient transmission from this receptor [2, 24].
Laboratory animals without the RXR-α gene cannot develop healthy heart tissue [25].
Laboratory animals without the RXR-α also cannot develop healthy eyes and vision [25].
Meanwhile, laboratory animals without RXR-β are sterile [1].
In most cases, these animals also fail to thrive during early development [1].
Laboratory animals without the RXR-β and RXR-γ genes have metabolic and behavioral defects [2].
9) Brain and Synaptic Plasticit
RXRs and RARs are important for neuronal and synaptic plasticity in the hippocampus [26].
However, in mice, excessive levels of vitamin A also result in cognitive deficits and reduced cell growth in the hippocampus [27].
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