paper published today in Scientific Reports describes the use of an experimental compound to reverse hair loss, hair whitening, and skin inflammation in mice fed a Western diet. Johns Hopkins scientists report that their compound halts the production of glycosphingolipids, or GSLs, that are major components of skin and other cell membranes.

"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," says Subroto Chatterjee, Ph.D., M.S., M.Sc., professor of pediatrics and medicine.

To determine how disrupting GSLs might affect skin appearance and color, and whether treatment with D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP)—a man-made compound that halts GSL production—would reverse any negative effects, the researchers fed a mouse model of atherosclerosis a Western diet high in fat and cholesterol, and a second group standard chow. All mice were fed their assigned diets from 12 weeks of age to 20 weeks. Compared to those fed standard chow, the mice that ate a Western diet lost hair, formed skin lesions, and suffered from hair whitening. These results became more severe when the mice continued eating a Western diet for 36 weeks, with 75% of the mice having skin, hair loss, and multiple skin lesions.

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From 20 to 36 weeks of age, mice in both groups were given varying amounts of D-PDMP, either in a capsule or as a liquid, while they ate the same diet. Mice that received 1 milligram and 10 milligrams of D-PDMP in a capsule per kilogram of body weight from 20 to 36 weeks while eating a Western diet started regaining hair and hair color, and their skin inflammation lessened. Treatment with 1 milligram of D-PDMP in a capsule per kilogram of body weight was as effective as 10 milligrams per kilogram as a liquid.

The research team then looked at the skin of the mice's under a microscope and found that mice eating the Western diet experienced an infiltration of neutrophils. Treatment with D-PDMP in a capsule significantly reduced the number of neutrophils, implying reduced skin inflammation and wounding.

Next, the researchers used mass spectrometry analysis to determine ceramide, glucosylceramide, and lactosylceramide levels in the mice. Compared to mice fed normal chow, those fed a Western diet had decreased total ceramide levels, decreased glucosylceramide, and nearly three times more lactosylceramide. Treatment with 1 milligram of D-PDMP in a capsule per kilogram of body weight or 10 milligrams of D-PDMP as a liquid per kilogram of body weight, however, noticeably increased ceramide levels to normal.

"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," says Chatterjee.