Human hair follicles (HFs) have a high demand for energy and biosynthesis precursors fulfilled mainly by aerobic glycolysis. HFs contain high levels of glycogen the main means by which glucose is stored in the body. In the liver lactate is converted to glucose and glycogen through gluconeogenesis via the Cori cycle. As the hair follicle is known to engage in aerobic glycolysis with the generation of lactate the aim of this study is to investigate both the role of glycogen in the hair follicle and whether the HF operates its own internal Cori cycle.
Glycogen was detected in the ORS and the cuticle of anagen HFs, significantly decreased in catagen and was absent in telogen HFs. Key enzymes of glycogen metabolism including glycogen phosphorylase (PYGL), phosphoglucomutase and glycogen synthase 1 were mainly in the ORS suggesting this compartment to be the key site of glycogen metabolism in the HF. Glucose uptake measured using a fluorescent derivative showed glucose localised as clear granules in the ORS of anagen HF, whereas catagen HF show limited glucose uptake. Treatment of cultured human HF with a PYGL inhibitor increased hair elongation in vitro and delayed anagen to catagen transition. The essential enzyme for gluconeogenesis, phosphoenolpyruvate carboxykinase (PCK1) was also present in the ORS. Primary ORS keratinocytes upon inducing lactic acidosis showed a significant increase in GYS1 expression and glycogen levels, confirming that the ORS is able to synthesise glycogen from lactate and engages in gluconeogenesis and glycogen synthesis.
In conclusion we show human HF have the capability to synthesise glycogen from lactic acid, implying an internal HF Cori cycle. Inhibiting glycogen degradation increased hair elongation suggesting glycogen may contribute to maintaining anagen. We suggest that HF may control their metabolism through a glycogen shunt, allowing metabolic homeostasis during large shifts in glucose supply and demand.

Outer root sheath is able to synthesise glycogen from lactate-investigating glycogen metabolism in human hair follicles.