| Summary: | 博士 === 國立成功大學 === 臨床醫學研究所 === 103 === The hair follicles and intradermal adipose tissue are close to each other either anatomically or functionally. Evidences and new nomenclature indicate intradermal adipose tissue as the adipose tissue above panniculus carnosus. The intradermal adipose tissue hosts the lower half of hair follicles in growth phase (anagen). The thickness of intradermal adipose tissue changes according to hair cycle propagation. However, the interaction between the two tissues in the cellular or molecular level is still largely unknown. This PhD theses focused on both the clinical and biological implications that adipose tissue might have on hair growth.
Leptin receptor is expressed specifically over the bulge area, where the hair epithelial stem cells reside, either in mouse vibrissa and pelage follicles and human scalp hair follicles. Leptin mRNA in the dermal adipose tissue is differentially expressed in different hair cycle stages, with lowest level in early anagen phase (growth phase) and highest level in telogen phase (resting phase). In vitro organ culture of vibrissa follicles from mice reveled that adipose-derived leptin inhibits the lengthening of anagen hair shafts. In db/db mice, the onset of second anagen was delayed and the hair wave propagation didn’t cover the whole back skin. The above findings suggest that leptin might modulate hair cycle propagation via the regulation on hair epithelial stem cells.
Clinically, a cross-sectional study was conducted to determine the association between body adiposity, as indexed by body mass index (BMI), and alopecia severity in men with androgenetic alopecia (AGA). 189 male patients were enrolled with a mean age of 30.8 years. The subjects with severe alopecia (grade V-VII) had higher BMI than subjects with mild to moderate alopecia (grade I-IV) (25.1 vs. 22.8 kg/m2, p=0.01). After multivariate adjustments, the risk for having severe alopecia was higher in the overweight or obese (BMI ≥24 kg/m2) subjects with male pattern AGA (odds ratio=3.52, p〈0.01). In early-onset male pattern AGA (n=46), the risk for having severe alopecia was also higher in the overweight or obese subjects (odds ratio=4.97, p=0.03). In another smaller series containing 26 AGA patients and 13 normal controls, the mean plasma level of leptin was higher in AGA patients with higher severity (grade IV-VI; 6823.7 pg/ml) comparing to patients with lower severity (grade I-III; 3544.3 pg/ml) (p〈0.05). The findings suggested that higher BMI was significantly associated with greater severity of hair loss in men with male pattern AGA, especially in those with early-onset AGA, and this phenomenon night be mediated by elevated level of leptin in the blood circulation. Analysis of intradermal adipose tissue from human scalp showed that inflammatory cytokines TNF-α was highly expressed in the balding scalp suggesting a “para-inflammation” status.
The reciprocal interaction between hair follicles and the adipose tissue is complicated. Furthermore, leptin from multiple sources including the endocrine, paracrine and autocrine routes further added the complexity. Further studies are required to dissect the regulatory loop. For clinical disease like AGA, the interplay of leptin, androgen inflammatory cytokines also needs further elucidation. In the future, we aim to find a novel treatment for AGA by manipulating adipose-derived factors.
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