Steno Diabetes Center Aarhus and Department of Hormonal Disorders, Aarhus University Hospital, Aarhus, Denmark.
Department of Clinical Pharmacology, Aarhus University, Aarhus, Denmark.
Eur J Endocrinol. 2021 May;184(5):687-697. doi: 10.1530/EJE-20-0713.
Activation of brown adipose tissue is a promising strategy to treat and prevent obesity and obesity-related disorders. Activation of uncoupling protein 1 (UCP1) leads to uncoupled respiration and dissipation of stored energy as heat. Induction of UCP1-rich adipocytes in white adipose tissue, a process known as 'browning', serves as an alternative strategy to increase whole body uncoupling capacity. Here, we aim to assess the association between parathyroid hormone (PTH) receptor expression and UCP1 expression in human adipose tissues and to study PTH effects on human white and brown adipocyte lipolysis and UCP1 expression.
A descriptive study of human neck adipose tissue biopsies substantiated by an interventional study on human neck-derived adipose tissue cell models.
Thermogenic markers and PTH receptor gene expression are assessed in human neck adipose tissue biopsies and are related to individual health records. PTH-initiated lipolysis and thermogenic gene induction are assessed in cultured human white and brown adipocyte cell models. PTH receptor involvement is investigated by PTH receptor silencing.
PTH receptor gene expression correlates with UCP1 gene expression in the deep-neck adipose tissue in humans. In cell models, PTH receptor stimulation increases lipolysis and stimulates gene transcription of multiple thermogenic markers. Silencing of the PTH receptor attenuates the effects of PTH indicating a direct PTH effect via this receptor.
PTH 1 receptor stimulation by PTH may play a role in human adipose tissue metabolism by affecting lipolysis and thermogenic capacity.
激活棕色脂肪组织是治疗和预防肥胖及肥胖相关疾病的一种有前景的策略。解偶联蛋白 1（UCP1）的激活导致储存能量的不偶联呼吸和耗散。在白色脂肪组织中诱导富含 UCP1 的脂肪细胞，即所谓的“褐变”，是增加全身解偶联能力的另一种策略。在这里，我们旨在评估甲状旁腺激素（PTH）受体表达与人类脂肪组织中 UCP1 表达之间的关联，并研究 PTH 对人类白色和棕色脂肪细胞脂肪分解和 UCP1 表达的影响。
对人体颈部脂肪组织活检进行描述性研究，并通过人体颈部来源的脂肪组织细胞模型进行干预性研究。
评估人体颈部脂肪组织活检中的生热标志物和 PTH 受体基因表达，并将其与个体健康记录相关联。在培养的人白色和棕色脂肪细胞模型中评估 PTH 引发的脂肪分解和生热基因诱导。通过 PTH 受体沉默研究 PTH 受体的参与。
PTH 受体基因表达与人类深颈脂肪组织中的 UCP1 基因表达相关。在细胞模型中，PTH 受体刺激增加脂肪分解并刺激多个生热标志物的基因转录。PTH 受体沉默减弱了 PTH 的作用，表明该受体通过直接作用于 PTH。
PTH 通过 PTH1 受体的刺激可能通过影响脂肪分解和产热能力在人类脂肪组织代谢中发挥作用。
