毛囊和皮內脂肪在解剖學上以及功能上有非常密切的相關性。最新研究及新的命名學將panniculus carnosus以上的皮膚脂肪層命名為皮內脂肪。在解剖學上，生長期毛囊的下半部生長於皮內脂肪之中；在功能上，毛囊和皮內脂肪都負責隔熱保暖的功能。在小鼠的皮膚，皮內脂肪的厚度會隨著皮膚的毛囊進入生長期而增厚，當毛囊進入休止期，皮內脂肪會再度變薄。但皮內脂肪和毛囊之間的相互調控還有很多未知，本論文的目的在研究脂肪組織對毛囊生長的影響。
在實驗室的研究我們著重在瘦素如何影響毛囊生長。在小鼠鬍鬚或背部毛囊或人類的頭皮毛囊，瘦素受體的表現在毛囊的膨大處，也就是毛囊上皮幹細胞所在的位置。小鼠的皮內脂肪中，瘦素mRNA的表現強度會隨著毛囊周期而改變，表現最高是在毛囊休止期時，而表現最低是在毛囊生長期時。在db/db小鼠中，第二個毛囊生長期的開始時間有延遲，散布的範圍也沒有片及整個背部皮膚。以上結果顯示瘦素可能藉由調節毛囊上皮幹細胞而調節毛囊週期生長。體外小鼠鬍鬚毛囊培養也顯示脂肪細胞所產生的瘦素會抑制毛幹的增長。
臨床上，我們進行一個橫斷面研究以了解肥胖的程度與雄性禿禿髮嚴重度的關聯性，肥胖程度以身體質量指數代表。我們收集189位男性雄性禿病人，平均年齡為30.8歲。比較有嚴重雄性禿的病人(嚴重度第五到七期)以及輕微雄性禿的病人(嚴重度一到四期)，嚴重雄性禿的組別有較高的身體質量指數(25.1 vs. 22.8 kg/m2, p=0.01)。以多變項分析之後，過重或肥胖的病人(身體質量指數≥24 kg/m2)有較高的機率產生嚴重雄性禿(odds ratio=3.52, p<0.01)。在早發性雄性禿的46位男性病人中，過重或肥胖的病人也有較高的機率產生嚴重雄性禿(odds ratio=4.97, p=0.03)。另一個小型研究包含26位雄性禿病人及13位頭髮正常的對照組，並測量其血漿中瘦素的平均值作比較，發現雄性禿較嚴重的病人(嚴重度第四到七期)比起較輕微的病人(嚴重度第一到三期) 有較高的瘦素血中濃度 (6823.7 pg/ml vs. 3544.3 pg/ml, p<0.05)。研究結果顯示高身體脂肪指數與嚴重男性雄性禿有顯著相關性，特別是在早發性雄性禿的男性病人身上。另外我們發現病人禿髮部位的皮內脂肪層有極高的TNF-α表現，代表禿髮部位處於”para-inflammation”的狀態。
毛囊和脂肪組織之間的影響是雙向的。此外，瘦素的來源可以是內分泌、旁分泌或自分泌，需要進一步研究才能解開此複雜的調節機制。對於臨床疾病如雄性禿，瘦素、雄性賀爾蒙及發炎激素如何共同造成疾病也需要進一步瞭解。我們希望未來的研究能找出調節皮內脂肪組織或其分泌的因子以治療禿髮疾病的新方法。

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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