Pharmacological Inhibition of DGAT1 Induces Sebaceous Gland Atrophy in Mouse and Dog Skin While Overt Alopecia Is Restricted to the Mouse

The study investigated the effects of DGAT1 inhibition on skin, using DGAT1 knockout mice and pharmacological inhibition with AZD7687 in both mice and dogs. DGAT1 is crucial for lipid synthesis, and its inhibition is explored for treating metabolic diseases. In mice, both genetic knockout and prolonged treatment with AZD7687 led to sebaceous gland atrophy and alopecia, with these effects being dose- and time-dependent and reversible. However, in dogs, prolonged AZD7687 treatment only caused sebaceous gland atrophy without hair loss or skin lesions. This suggests a species-specific response to DGAT1 inhibition, with mice being particularly sensitive. The findings indicate that while DGAT1 inhibitors may not affect human skin in the same way as in mice, careful monitoring for skin changes is necessary in human clinical trials of DGAT1 inhibitors.