Effect of Free Long-Chain Fatty Acids on Anagen Induction: Metabolic or Inflammatory Aspect?

Abstract

Hair growth is a highly complex process regulated at multiple levels, including molecular pathways, stem cell behavior, metabolic processes, and immune responses. The hair follicle exhibits metabolic compartmentalization, with some cells relying on glycolysis and others on oxidative phosphorylation. Interestingly, in mice, the onset of the anagen phase can be stimulated by locally suppressing oxidative phosphorylation in the skin. This study showed that topical application of palmitate or oleate accelerated the onset of anagen in mice, while lactate, the end product of glycolysis, delayed it. We also investigated the effects of fatty acids on cytokine production in various human cell cultures. Fatty acids did not induce a cytokine response in fibroblasts or keratinocytes but significantly affected monocytes. Specifically, palmitic acid induced the production of TNF-α, IL-8, and CCL2. Oleic acid, however, elicited almost no response. By comparing the "metabolic" and "inflammatory" hypotheses of anagen stimulation, the results of our study suggest that metabolic regulation holds significant promise for influencing hair growth.

Keywords: free fatty acids; glycolysis; hair growth; inflammation; lactate; metabolic reprogramming.

Figure 1

Effect of fatty acid mixture on the appearance of we/we wal/wal mice. (a)—control, (b)—mice after 17 days from the beginning of treatment. It can be seen that the treatment causes an increase in the contrast of skin coloration.

Figure 2

Effects of fatty acid mixture on the appearance of aged we/we wal/wal mice. Individual mice are represented vertically. Treatments were performed twice (labeled on the left). Both treatments resulted in enhancement of the dark components of the skin pattern.

Figure 3

Effect of fatty acid treatment on the onset of anagen in C57Bl/6 mice. (a)—control, 57 days old; (b)—palmitic acid, 54 days old; (c)—oleic acid, 54 days old; (d)—same mouse as in 3c at 57 days old; (e)—graph of the appearance of gray skin coloration when treated with different fatty acids. * p < 0.05, ** p < 0.01.

Figure 4

The effect of lactate on the onset of the anagen in C57Bl/6 mice. (a)—mice treated with lactate that reached the age of 60 days. The arrow shows a mouse in anagen. (b)—graph of the appearance of gray coloration of the skin. *** p < 0.005.

Figure 5

Induction of inflammatory factors in various human cells by fatty acids. Medians and standard deviations are shown. *** p < 0.005.

Figure 6

The process of skin color change during induction of anagen. (a)—is the day before the mouse turned gray, (b)—is the day when it started to turn gray, (c)—is the day after it started to turn gray. It can be seen that there is a clear difference.