Highlights
- •Western diet (WD) facilitated the development of dermatitis in C57BL/6 mice.
- •WD-exacerbated dermatitis is sex-dependent with higher incidence in female mice.
- •Reduced TGR5 and S1PR2 signaling was found in the dermis of WD-fed mice.
- •WD-induced lesional skin has activated TGR5 and S1PR2 signaling.
- •Cholestyramine supplementation reduced dermatitis in WD-fed mice.
Abstract
Background
Dietary interventions are implicated in the development of atopic dermatitis, psoriasis,
and acne.
Objective
To investigate the effect of diet and the bile acid (BA) receptors, such as TGR5 (Takeda
G protein receptor 5) and S1PR2 (sphingosine-1-phosphate receptor 2) in the development
of dermatitis.
Methods
C57BL/6 mice were fed a control diet (CD) or Western diet (WD) since weaning until
they were 10 months old followed by analyzing histology, gene expression, and BA profiling.
Results
Mice developed dermatitis as they aged and the incidence was higher in females than
males. Additionally, WD intake substantially increased the incidence of dermatitis.
Cutaneous antimicrobial peptide genesS100A8, S100A9, and Defb4 were reduced in WD-fed mice, but increased when mice developed skin lesions. In addition,
Tgr5 and TGR5-regulated Dio2 and Nos3 were reduced in WD intake but induced in dermatitic lesions. Trpa1 and Trpv1, which mediate itch, were also increased in dermatitic lesions. The expression of
S1pr2 and genes encoding sphingosine kinases, S1P phosphatases, binding protein, and transporter
were all reduced by WD intake but elevated in dermatitic lesions. Furthermore, dermatitis
development increased total cutaneous BA with an altered profile, which may change
TGR5 and S1PR2 activity. Moreover, supplementation with BA sequestrant cholestyramine
reduced epidermal thickening as well as cutaneous inflammatory cytokines.
Conclusion
In summary, activation of TGR5 and S1PR2, which regulate itch, keratinocyte proliferation,
metabolism, and inflammation, may contribute to WD-exacerbated dermatitis with Th2
and Th17 features. In addition, elevated total BA play a significant role in inducing
dermatitis and cutaneous inflammation.
Keywords
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Article info
Publication history
Published online: June 08, 2019
Accepted:
May 28,
2019
Received in revised form:
May 9,
2019
Received:
October 15,
2018
Identification
Copyright
© 2019 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.
