Fats are essential for human health. Dietary fatty acides (FAs) are either saturated (e.g. 16:0 palmitic acid, PA), monounsaturated (e.g. 18:1 oleic acid, OA), or polyunsaturated (e.g. 18:2 linoleic acid, LA). Depending on the double bond position counting from the methyl end of the FA carbon chain, polyunsaturated FAs (PUFAs) include omega-6 (n-6) and omega-3 (n-3) FAs. It is generally believed that intake of n-3 FAs (e.g. docosapentaenoic acid, DPA or eicosapentaenoic acid, EPA) inhibits inflammation and prevents inflammatory diseases, whereas saturated fat ingestion increases chronic inflammation and promotes obesity-associated diseases, including cardiovascular disease, type II diabetes, and multiple types of cancer. However, mounting evidence from recent randomized clinical trials does not support the favorable benefits of dietary n-3 FA supplements, and the controversy of saturated fat on adverse health effects also appears far from conclusive. These conflicting results highlight the mechanistic gap in how metabolism of different fats, in particular n-3 and saturated FAs, regulate cellular function and inflammatory responses in vivo.

Fats are insoluble in aqueous environments. Fatty acid binding proteins (FABPs) are a group of evolutionarily conservative proteins evolved to facilitate FA transport and responses across species. The FABP family consists of at least 9 members, which were named according to their distinct pattern of tissue distribution. Epidermal FABP (E-FABP, also known as FABP5) is mainly expressed in the skin. Previous studies from Dr. Li’s group demonstrated that E-FABP is also expressed in different subsets of immune cells, regulating immune cell lipid metabolism and function. This new study led by Dr. Jiaqing Hao, an Associate Research Scientist in Dr. Li’s group, further demonstrated that consumption of fish oil HFD induces hair loss via E-FABP-dependent immunoregulatory effects. Following lipid absorption, n-3 FAs were preferably enriched in the skin, where E-FABP expression in CD207+ resident skin macrophages play an essential role in mediating n-3 FA/ROS/IL-36 signaling, which further promotes infiltration/activation of CD207- myeloid macrophages leading to TNF-a-mediated immune inhibition of hair follicle stem cells. Altogether, these studies not only provide a cellular and molecular mechanism by which consumption of n-3 FAs activates skin macrophages through E-FABP/ROS/IL-36/TNF-a signaling, thus promoting fish oil-induced hair loss, but also have clinical implications for understanding the etiology of dietary fat-associated hair health.

The study was funded by the NIH. In addition to Drs. Hao and Li, the team included Rong Jin, Jun Zeng, Yuan Hua, Matthew S. Yorek, Lianliang Liu, Anita Mandal, Junling Li, Huaiyu Zheng, Yanwen Sun, Yanmei Yi, Di Yin, Qi Zheng, Xiaohong Li, Chin K. Ng, Eric C. Rouchka, Nejat K. Egilmez, and Ali Jabbari.

The article can be viewed at:
https://www.cell.com/cell-reports/pdf/S2211-1247(22)01692-8.pdf