Obesity is considered a world-wide epidemic and has been associated with many diseases in humans, including heart disease and diabetes. Despite this, the precise mechanisms whereby obesity effects organ dysfunction are not known.
In a recent article published in Nature, researchers from Tokyo Medical and Dental University (TMDU) identified a mechanism whereby genetically induced obesity or eating a high-fat diet can lead to hair thinning and loss in laboratory mice.
Hair follicles are tiny epithelial organs that grow hair, thanks to the action of hair follicle stem cells (HFSCs). These cells replenish themselves at the start of every new hair follicle cycle, which enables us to grow our hair back after it falls out naturally. Unfortunately, HFSCs become depleted as we age, which leads to miniaturization of hair follicles and consequent thinning of our hair.
The researchers from TDMU used mouse models to investigate whether genetically induced obesity and eating a high-fat diet accelerate hair loss, and to establish the molecular mechanisms involved.
The experts found that both obesity and eating a high-fat diet can lead to depletion of hair follicle stem cells (HFSCs) and that these cells begin to differentiate into keratinized skin cells, rather than forming new hair follicles. This blocks hair follicle regeneration and ultimately results in the loss of hair follicles. Even when young mice are fed a high-fat diet for only four consecutive days, their HFSCs show increased oxidative stress and begin to exhibit abnormal differentiation into skin cells.
“High-fat diet [HFD] feeding accelerates hair thinning by depleting HFSCs that replenish mature cells that grow hair, especially in old mice,” explained study lead author Hironobu Morinaga. “We compared the gene expression in HFSCs between HFD-fed mice and standard diet-fed mice and traced the fate of those HFSCs after their activation.”
“We found that those HFSCs in HFD-fed obesed mice change their fate into the skin surface corneocytes or sebocytes that secrete sebum upon their activation. Those mice show faster hair loss and smaller hair follicles along with depletion of HFSCs.”
The data demonstrate that stem cell inflammatory signals induced by obesity robustly repress organ regeneration signals, thereby accelerating the miniaturization of the hair follicles.
“The gene expression in HFSCs from the high-fat-fed mice indicated the activation of inflammatory cytokine signaling within HFSCs,” explained senior author Emi K. Nishimura. “The inflammatory signals in HFSCs strikingly repress Sonic hedgehog signaling that plays a crucial role in hair follicle regeneration in HFSCs”.
The researchers also found that re-activation of the Sonic hedgehog signaling pathway can reverse the depletion of HFSCs. “This could prevent the hair loss brought on by the high-fat diet,” said Nishimura. The discovery could lead to new methods for preventing and treating hair thinning as well to enhanced understanding of obesity-related diseases.