Delayed Hair Follicle Morphogenesis and Hair Follicle Dystrophy in a Lipoatrophy Mouse Model of Pparg Total Deletion

PPAR gamma regulates multiple aspects of skin physiology, including sebocyte differentiation, keratinocyte proliferation, epithelial stem cell survival, adipocyte biology, and inflammatory skin responses. However, the effects of its global deletion, namely of nonredundant key functions of PPAR gamma signaling in mammalian skin, are yet unknown because of embryonic lethality. Here, we describe the skin and hair phenotype of a whole-body PPAR gamma-null mouse Pparg(Delta/Delta)), obtained by preserving PPARg expression in the placenta. Pparg(Delta/Delta) mice exhibited total lipoatrophy and complete absence of sebaceous glands. Right after birth, hair follicle HF) morphogenesis was transiently delayed, along with reduced expression of HF differentiation markers and of transcriptional regulators necessary for HF development. Later, adult Pparg(Delta/Delta) mice developed scarring alopecia and severe perifollicular inflammation. Skin analyses in other models of lipodystrophy, AZIP(tg/+) and Adipoq-Cre(tg/+)Pparg(fl/fl) mice, coupled with skin graft experiments, showed that the early defects observed in hair morphogenesis were caused by the absence of adipose tissue. In contrast, the late alteration of HF cycle and appearance of inflammation were observed only in Pparg(Delta/Delta) mice and likely were due to the lack sebaceous glands. Our findings underscore the increasing appreciation for the importance of adipose tissue-mediated signals in HF development and function.