Mammalian Epidermis: A Compendium of Lipid Functionality

Abstract

Mammalian epidermis is a striking example of the role of lipids in tissue biology. In this stratified epithelium, highly specialized structures are formed that leverage the hydrophobic properties of lipids to form an impermeable barrier and protect the humid internal environment of the body from the dry outside. This is achieved through tightly regulated lipid synthesis that generates the molecular species unique to the tissue. Beyond their fundamental structural role, lipids are involved in the active protection of the body from external insults. Lipid species present on the surface of the body possess antimicrobial activity and directly contribute to shaping the commensal microbiota. Lipids belonging to a variety of classes are also involved in the signaling events that modulate the immune responses to environmental stress as well as differentiation of the epidermal keratinocytes themselves. Recently, high-resolution methods are beginning to provide evidence for the involvement of newly identified specific lipid molecules in the regulation of epidermal homeostasis. In this review we give an overview of the wide range of biological functions of mammalian epidermal lipids.

Saprophytic bacteria and fungi colonize stearoyl coenzyme‐A desaturase‐1 knockout skin

“…It is noteworthy that all bacteria found at higher relative abundance in the Scd1 ΔK14 group are Gram positives. Sebum fatty acids generally display greater antimicrobial activity against Gram positives than Gram negatives, potentially secondary to the hydrophobic compound protection the lipopolysaccharide coat provides the latter 2,25,26 . In Scd1 ΔK14 skin, decreased sebaceous‐derived lipids and unsaturated fatty acids may therefore allow Gram positives to thrive.…”

“…Sebum fatty acids generally display greater antimicrobial activity against Gram positives than Gram negatives, potentially secondary to the hydrophobic compound protection the lipopolysaccharide coat provides the latter. 2,25,26 In Scd1 ΔK14 skin, decreased sebaceous-derived lipids and unsaturated fatty acids may therefore allow Gram positives to thrive. Sebaceous gland hypoplasia in Scd1 ΔK14 mice may also account for observed increased alpha diversity, as sebaceous glands normally stabilize skin bacterial and fungal communities; in populations like infants with immature sebaceous glands, the skin microbiome is unstable.…”

“…In the stratum corneum, the cornified envelope, lipid envelope and lipid matrix physically minimize skin permeability. The chemical antiseptic barrier provided by skin lipids consists of direct microorganism targeting via keratinocyte‐derived free sphingoid bases and sebum‐derived free fatty acids, and indirect targeting through immune system modulation 2–4 …”

“…Lipids also support lipophilic skin commensals. Areas of the body rich in sebaceous glands are hydrophobic havens for obligatory and facultative anaerobes, and free fatty acids freed by bacterial and host lipases facilitate bacterial adhesion and decrease pathogen competition 2 . Moreover, sebum and stratum corneum lipids are used by auxotrophic Malassezia and Corynebacterium species unable to produce their own lipids 5 .…”

“…The chemical antiseptic barrier provided by skin lipids consists of direct microorganism targeting via keratinocyte-derived free sphingoid bases and sebum-derived free fatty acids, and indirect targeting through immune system modulation. [2][3][4] Lipids also support lipophilic skin commensals. Areas of the body rich in sebaceous glands are hydrophobic havens for obligatory and facultative anaerobes, and free fatty acids freed by bacterial and host lipases facilitate bacterial adhesion and decrease pathogen competition.…”