Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
J Obes. 2023 Jan 19;2023:5651084. doi: 10.1155/2023/5651084. eCollection 2023.
The objective of this study was to functionally analyze the correlation of key histological features in brown adipose tissue (BAT) with clinical metabolic traits in nonhuman primates.
Axillary adipose tissue biopsies were collected from a metabolically diverse nonhuman primate cohort with clinical metabolism-related data. Expression of tyrosine hydroxylase (TH), uncoupling protein 1 (UCP1), cluster of differentiation 31 (CD31), cytochrome c oxidase subunit 4 (COX IV), beta-3 adrenergic receptor (3-AR), and adipose cell size were quantified by immunohistochemical analysis. Computed tomography scans were performed to assess body composition.
Tyrosine hydroxylase was negatively correlated with whole body fat mass as a percentage of body weight ( = 0.004) and was positively correlated with the density of UCP1 ( = 0.02), COX IV ( = 0.006), CD31 ( = 0.007), and cell density ( = 0.02) of the BAT samples. Beta-3 adrenergic receptor abundance had a weak positive correlation with COX IV ( = 0.04) in BAT but did not significantly correlate to UCP1 or TH expression in BAT.
Our findings highlight that there is a disparity in innervation provided to BAT based on body composition, as seen with the negative association between TH, a marker for innervation, and adiposity. These findings also support the importance of innervation in the functionality of BAT, as TH abundance not only supports leaner body composition but is also positively correlated with known structural elements in BAT (UCP1, COX IV, CD31, and cell density). Based on our observations, 3-AR abundance does not strongly drive these structural elements or TH, all of which are known to be important in the function of brown adipose tissue. In effect, while the role of other receptors, such as 2-AR, should be reviewed in BAT function, these results support the development of safe sympathetic nervous system stimulants to activate brown adipose tissue for obesity treatment.
本研究旨在对棕色脂肪组织（BAT）的关键组织学特征与非人类灵长类动物临床代谢特征的相关性进行功能分析。
从具有临床代谢相关数据的代谢多样化非人类灵长类动物队列中采集腋窝脂肪组织活检。通过免疫组织化学分析定量测定酪氨酸羟化酶（TH）、解偶联蛋白 1（UCP1）、分化簇 31（CD31）、细胞色素 c 氧化酶亚基 4（COX IV）、β-3 肾上腺素能受体（3-AR）和脂肪细胞大小。进行计算机断层扫描以评估身体成分。
TH 与全身脂肪量占体重的百分比呈负相关（r=0.004），与 BAT 中 UCP1（r=0.02）、COX IV（r=0.006）、CD31（r=0.007）和细胞密度（r=0.02）的密度呈正相关。β-3 肾上腺素能受体丰度与 BAT 中的 COX IV 呈弱正相关（r=0.04），但与 BAT 中的 UCP1 或 TH 表达无显著相关性。
我们的研究结果表明，根据身体成分，BAT 所提供的神经支配存在差异，TH（神经支配的标志物）与肥胖呈负相关。这些发现还支持神经支配对 BAT 功能的重要性，因为 TH 丰度不仅支持更瘦的身体成分，而且还与 BAT 中的已知结构元素（UCP1、COX IV、CD31 和细胞密度）呈正相关。根据我们的观察，3-AR 丰度不会强烈驱动这些结构元素或 TH，所有这些在棕色脂肪组织的功能中都是重要的。实际上，虽然其他受体（如 2-AR）在 BAT 功能中的作用应该得到审查，但这些结果支持开发安全的交感神经系统刺激物来激活棕色脂肪组织以治疗肥胖症。
