快樂小藥師 Im pharmacist nichts glücklich

從NEJM節錄下來的

The Activation of Brown Adipose Tissue 

Stimulation of β₃-adrenergic receptors leads to the dramatic increase in the intracellular concentration of triiodothyronine (T₃) by means of the type 2 5' deiodinase (D2); T₃ in turn stimulates the transcription of uncoupling protein 1 (UCP1), which causes the leakage of protons from the inner membrane of the mitochondria, hence dissipating energy in the form of heat. The abbreviation cAMP denotes cyclic adenosine monophosphate, CRE cAMP response element, T₄ thyroxine, and TRE thyroid hormone response element.

Becoming a Brown Fat Cell.

A recent study by Seale et al.² showed that although some brown fat cells are derived from precursors that originate from Myf5-expressing dermomyotome (derived from paraxial mesoderm), other brown fat cells have a different origin. White adipocytes are Myf5-negative and are derived from blood-vessel–associated pericyte-like cells originating from the lateral plate mesoderm.⁴ Two pathways are therefore evident, one that involves cells that express or have expressed the Myf5 transcription factor (which has a key role in regulating muscle differentiation) and another that does not involve such cells. Interscapular and perinephritic brown fat cells are derived from the Myf-positive pathway, whereas brown adipocytes that are induced to differentiate by adrenergic stimulation are derived from the Myf-negative pathway, as are white adipocytes.

那個褐色脂肪組織是做什麼的呢？

簡單的說：

褐色脂肪組織於新鮮活體狀態呈褐色分布在全身上下五處，分別為腦後、背部肩胛骨、腋下和心臟的大動脈周圍，還有腎臟周圍。其脂肪細胞內儲存多量之小型油滴，細胞核呈橢圓形且細胞質內富含粒腺體，與白色脂肪組織最大的不同在於褐色脂肪組織能夠發熱。褐色脂肪細胞在脂紡氧化之過程，不形成 ATP 而將所含之能量以熱能形式釋放，提供動物體溫與熱能之需求，在小型哺乳動物之體溫維持上與動物冬眠之甦醒時，扮演極重要之角色（冬眠中的動物能夠使生命繼續維持，就是因為褐色脂肪組織能夠直接燃燒脂肪，依靠其產生的熱來保護心臟等重要的器官）。人類之褐色脂肪組織從出生後到生命之前十年內會逐漸減少，而白色脂肪組織則相反，所以成為成人之脂肪組織。

脂肪細胞內的脂質氧化作用，和粒腺體內的未連結蛋白（uncoupling proteins，UCP1）及脂肪細胞膜上的β3腎上腺受體（β3-adrenergic receptor）有關：UCP1的基因表現使能量以熱的形式散出；β3腎上腺受體被活化時，脂肪組織會有產熱反應。近來研究認為，脂肪中的UCP1與β3腎上腺受體不僅存在褐色脂肪細胞內，在白色脂肪組織亦可偵測到UCP1存在及具備β3腎上腺受體功能。

以老鼠來說，當褐色脂肪組織的功能活化到最大，能夠產生全身代謝量的的熱。所以，當褐色組織完全不起作用，而老鼠食量也沒有減少，就會產生肥胖的結果。

資料來源：

The Origins of Brown Adipose Tissue Volume 360:2021-2023