The metabolic underpinnings of sebaceous lipogenesis

Sebaceous glands synthesize and secrete sebum, a mélange of lipids and other cellular products that safeguards the mammalian integument. Differentiating sebocytes delaminate from the basal membrane and dislodge towards the gland's middle, where they eventually undergo a poorly understood death mode in which the whole cell becomes a secretion product (holocrine secretion). Supported by recent transcriptomics data, this review examines the idea that peripheral sebocytes have a remarkable ability to draw nutrients from the blood and become committed to unrestrainedly invest all available resources into synthetic processes for accomplishing sebum synthesis, thereby exploiting core metabolic fluxes as glycogen turnover, glutamine-directed anaplerosis, the pentose phosphate pathway and de novo lipogenesis. Finally, we propose that metabolic-driven processes are an important mechanistic component of holocrine secretion. A deeper understanding of these metabolic adaptations could indicate novel strategies for modulating sebum synthesis, a key pathogenic factor in acne and other skin diseases.