Nature: Obesity really causes hair loss!

As a miniature epithelial organ that grows hair, hair follicles become smaller with aging, and hair follicle stem cells (HFSCs) are depleted and cause hair loss
.

Almost every hair follicle contains a group of hair follicle stem cells, these stem cells will differentiate to form hair

Theoretically, as long as there are hair follicle stem cells, there will be no baldness.
However, recent studies have found that hair follicle stem cells still exist in the hair loss areas of people with hair loss, but these stem cells cannot work and are in a dormant state
.

Although obesity is considered a risk factor for androgenetic alopecia, the specific mechanism is unknown
.

On June 23, 2021, the Emi K.
Nishimura research team of Tokyo Medical and Dental University published an article in Nature that revealed the stem cell mechanism of obesity-induced hair loss
.

In 2019, the research team found that the expression of COL17A1 in the skin was reduced in the injured state, causing skin aging
.

The skin of COL17A1 knockout mice is more prone to aging and the wound healing ability is reduced

Obesity causes hair loss in mice

Obesity causes hair loss in mice Obesity causes hair loss in mice

The researchers found that there was no alopecia in the 20-month-old old mice on a normal diet, but the obese old mice caused by a high-fat diet for one week showed obvious alopecia
.

In addition, two-month-old adult mice also showed significant hair loss after nearly 10 weeks of high-fat diet

Aging and high-fat diet cause the number of hair follicles to decrease

Aging and a high-fat diet cause a decrease in the number of hair folliclesAging and a high-fat diet cause a decrease in the number of hair follicles

They also found that aging mice do have a significant reduction in the number of hair follicles, and obesity caused by a high-fat diet can also cause this hair follicle reduction
.

Immunofluorescence experiments found that the number of hair follicle stem cells in the bulge area and basal cells decreased after a high-fat diet

Hair follicle stem cell lineage found that the hair follicle stem cells of mice on a normal diet were located in the bulge area of ​​the outer root sheath of the hair follicle, and some of them differentiated into hair shafts
.

However, after 3 months of high-fat diet, the number of hair follicle stem cells in the bulge area was significantly reduced, and the differentiated progeny cells migrated closer to the skin

In order to further find the mechanism of high-fat diet on hair follicle stem cell fate regulation, they found through single-cell sequencing that the expression of Col17a1, a molecule that regulates hair follicle stem cell self-renewal and aging, decreased in aging mice, but did not change in obese mice
.

This indicates that the mechanisms of hair loss after old age and obesity may be different

MAPK and SHH signaling (sonic hedgehog pathway, which regulates cell proliferation and cell differentiation) pathways are down-regulated in hair follicle stem cells of obese mice, and SHH signaling is also suppressed during hair follicle growth
.

After the tool mouse specifically inhibits the SHH signal in the hair follicle stem cells, this kind of mouse has obvious hair reduction, and the fate and differentiation of the hair follicle stem cells are disordered, which is similar to the effect of obese mice on hair
.

Molecular biology experiments found that the expression of interleukin 1β (IL1β) and oxidative damage markers in hair follicle stem cells of obese mice increased
.

In addition, lipid droplets in mouse hair follicle stem cells were abnormally enriched after a long-term high-fat diet

IL-1β, IL-6, lipid mixture or hydrogen peroxide can inhibit SHH signal in hair follicle stem cells
.

It shows that these inflammatory signal factors and oxidative stress inhibit SHH signal in hair follicle stem cells

Specific activation of SHH to prevent hair loss caused by obesity

Specific activation of SHH to prevent hair loss caused by obesity Specific activation of SHH to prevent hair loss caused by obesity

They further used the tool mice to specifically activate SHH signals during a high-fat diet to significantly inhibit hair loss caused by obesity
.
In addition, after a week of treatment with small molecule drugs that activate SHH signals, it can also effectively treat hair loss caused by obesity
.
These results indicate that the SHH signal disorder caused by high-fat diet is the key mechanism that causes hair loss
.

In summary, this article found that the abnormal activation of the inflammatory signal of hair follicle stem cells caused by obesity further inhibits the SHH signal that regulates the proliferation and differentiation of stem cells, accelerates the shrinkage of hair follicles and hair loss.

Original source:

Original source:

Morinaga, H.
, Mohri, Y.
, Grachtchouk, M.
et al.
Obesity accelerates hair thinning by stem cell-centric converging mechanisms.
Nature (2021).
https://doi.
org/10.
1038/s41586-021-03624- x.

Obesity accelerates hair thinning by stem cell-centric converging mechanisms.
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