PTH and PTHrP treatment of primary adipocytes. Mus musculus

Parathyroid hormone (PTH) and PTH-related protein (PTHrP) are involved in cachexia associated with chronic kidney disease and cancer respectively. Tumor-derived PTHrP triggers adipose tissue browning and thereby leads to wasting of fat tissue in tumor-bearing mice. Similarly, elevated in 5/6 nephrectomized mice, PTH stimulates adipose tissue browning and wasting. Mice lacking the PTH/PTHrP receptor in their fat tissue are resistant to wasting of both adipose tissue and skeletal muscle. Therefore, the PTH/PTHrP signaling in adipocytes should activate various pathways that contribute to hypermetabolism and muscle wasting. Overall design: Inguinal stroma-vascular fractions were cultured and differentiated into primary adipocytes. 8 days after differentiation, cells were treated with PTH(1-34) or PTHrP(1-34) (100 ng/ml each) for 4 hours.

甲状旁腺激素（Parathyroid hormone, PTH）与甲状旁腺激素相关蛋白（PTH-related protein, PTHrP）分别参与慢性肾病相关恶病质与癌症相关恶病质的发生发展。肿瘤源性PTHrP可诱导脂肪组织褐变（adipose tissue browning），进而引发荷瘤小鼠的脂肪组织消耗。与之类似，在5/6肾切除小鼠（5/6 nephrectomized mice）中表达上调的PTH，同样可诱导脂肪组织褐变并引发脂肪消耗。脂肪组织中缺失PTH/PTHrP受体的小鼠，对脂肪组织与骨骼肌（skeletal muscle）的消耗均产生抵抗。由此可见，脂肪细胞中的PTH/PTHrP信号通路可激活多条参与代谢亢进（hypermetabolism）与肌肉消耗的信号通路。整体实验设计：取腹股沟基质血管组分（stroma-vascular fractions）进行体外培养，并诱导分化为原代脂肪细胞（primary adipocytes）；于分化完成8天后，分别用PTH(1-34)或PTHrP(1-34)（终浓度均为100 ng/ml）处理细胞4小时。