Studies in mice have shown how a compound that blocks production of glycosphingolipids (GSLs) can reverse hair whitening, hair loss, and skin inflammation, conditions which previous studies have linked with high-fat, high-cholesterol diets in humans.
The researchers, headed by Subroto Chatterjee, Ph.D., professor of pediatrics and medicine at the Johns Hopkins University School of Medicine, hope that their findings will provide insights into the effects of diet and aging on hair biology, balding, and skin inflammation. They suggest that an encapsulated formulation of the synthetic GSL inhibitor, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP), could also form the basis of new treatments for human hair loss and skin wounds. “Further research is needed, but our findings show promise for someday using the drug we developed for skin diseases such as psoriasis, and wounds resulting from diabetes or plastic surgery,” Dr. Chatterjee states.
“…biopolymer-encapsulated D-PDMP could be a promising agent for therapeutic use for multiple skin and hair disorders via topical use and/or by oral delivery,” the team concluded in its paper titled, “Inhibition of glycosphingolipid synthesis reverses skin inflammation and hair loss in ApoE−/− mice fed western diet” which was published in Scientific Reports.
GSLs are a type of fat that represents a key component of cell membranes, and which impacts on a range of biological functions. Previous studies have shown that GSLs are found in high amounts in cells that make up the upper layer of the skin, as well as in keratinocytes that are involved in skin, eye, and hair pigmentation.
Experiments have also demonstrated that in mice, a high-fat diet and aging are both among risk factors for developing dermatitis, and the new studies by Dr. Chatterjee’s team, in a mouse model of atherosclerosis (ApoE–/– mice), have now demonstrated how a Western diet that is high in fat and cholesterol promotes the formation of skin lesions, and leads to hair whitening and eventually hair loss. “This is the first time we report these results of skin whitening in Apo E−/− mice fed high fat and high cholesterol,” the team writes.
When researchers fed ApoE–/– mice with a western diet, from the age of 12 to 20 weeks, the animals developed modest increase in hair whitening, loss of hair and skin lesion formation, compared with animals fed a normal, chow diet. If the diet was continued from 20 weeks to 36 weeks of age the animals then developed marked hair loss and skin whitening, and many small and large inflammatory skin lesions.
When groups of the western diet-fed ApoE–/– mice were treated from 20-36 weeks of age using either unencapsulated liquid, or encapsulated oral formulations of the synthetic GSL inhibitor D-PDMP, they showed markedly reduced hair discoloration, hair loss, and skin inflammation. The treatment also promoted wound healing. A dosage of 1 mg/kg encapsulated D-PDMP (BPD) was just as effective as 10 mg/kg bodyweight unencapsulated liquid D-PDMP.
Further analysis of the animals’ skin showed that BPD administration reduced infiltration of inflammatory neutrophils into different areas of the skin in the western diet-fed animals, and also reduced levels of tumor necrosis factor (TNF)-stimulated gene 6 (TSG-6), a protein that is stimulated by the pro-inflammatory cytokine TNF.
Mass spectrometry analyses showed that compared with mice fed regular chow, the western diet-fed animals also had lower levels of ceramide and mohexosylceramide, but higher levels of lactosylceramide. Ceramides are a type of lipid that helps to protect the skin’s moisture, while lactosylceramide, a derivative of ceramide, activates inflammation. Again, BPD therapy led to increased total ceramide and glycosylceramide levels, and reduced levels of lactosylceramide in the skin. The liquid D-PDMP was also effective, but at 10 times higher concentrations than the encapsulated BDP.
“In conclusion, to our best knowledge this is the first report wherein we show that feeding a western diet to ApoE−/− mice could have profound effects on the skin such as whitening inflammation, hair discoloration, and hair loss,” the authors write. They note that the observed progression of hair whitening and then balding in the western diet-fed ApoE–/– mice is also “identical” to that which occurs as part of normal human aging. “Our findings show that a western diet causes hair loss, hair whitening and skin inflammation in mice, and we believe a similar process occurs in men who lose hair and experience hair whitening when they eat a diet high in fat and cholesterol,” adds Dr. Chatterjee. And while more research will obviously be needed, he believes that “hopefully someday in the future this can mean faster, more effective recovery from baldness, hair whitening in aging populations and wound healing.”
The authors say they hope that their work will also help scientists derive a greater understanding of how diet and aging impact on our skin and hair. “We expect that the observations we describe in this work could bolster further research to elaborate the biology of skin, hair coloration, and hair health, in relevance to diet and inflammation, aging and focused on the role of glycosphingolipids.”