College of Pharmacy, Yonsei University, Incheon, 21983, South Korea.
Center for Integrative Metabolic and Endocrine Research, Wayne State University School of Medicine, Detroit, MI, 48201, USA.
Sci Rep. 2017 Jan 3;7:39794. doi: 10.1038/srep39794.
Sustained β3 adrenergic receptor (ADRB3) activation simultaneously upregulates fatty acid synthesis and oxidation in mouse brown, beige, and white adipose tissues; however, the cellular basis of this dual regulation is not known. Treatment of mice with the ADRB3 agonist CL316,243 (CL) increased expression of fatty acid synthase (FASN) and medium chain acyl-CoA dehydrogenase (MCAD) protein within the same cells in classic brown and white adipose tissues. Surprisingly, in inguinal adipose tissue, CL-upregulated FASN and MCAD in distinct cell populations: high MCAD expression occurred in multilocular adipocytes that co-expressed UCP1+, whereas high FASN expression occurred in paucilocular adipocytes lacking detectable UCP1. Genetic tracing with UCP1-cre, however, indicated nearly half of adipocytes with a history of UCP1 expression expressed high levels of FASN without current expression of UCP1. Global transcriptomic analysis of FACS-isolated adipocytes confirmed the presence of distinct anabolic and catabolic phenotypes, and identified differential expression of transcriptional pathways known to regulate lipid synthesis and oxidation. Surprisingly, paternally-expressed genes of the non-classical gene imprinted network were strikingly enriched in anabolic phenotypes, suggesting possible involvement in maintaining the balance of metabolic phenotypes. The results indicate that metabolic heterogeneity is a distinct property of activated beige/brite adipocytes that might be under epigenetic control.
β3 肾上腺素能受体 (ADRB3) 的持续激活同时上调了小鼠棕色、米色和白色脂肪组织中的脂肪酸合成和氧化；然而，这种双重调节的细胞基础尚不清楚。用 ADRB3 激动剂 CL316,243 (CL) 处理小鼠，在经典棕色和白色脂肪组织中，同一细胞内的脂肪酸合酶 (FASN) 和中链酰基辅酶 A 脱氢酶 (MCAD) 蛋白表达增加。令人惊讶的是，在腹股沟脂肪组织中，CL 上调了两种不同细胞群的 FASN 和 MCAD：高 MCAD 表达发生在多泡脂肪细胞中，这些细胞共表达 UCP1+，而高 FASN 表达发生在缺乏可检测到 UCP1 的少泡脂肪细胞中。然而，UCP1-cre 的遗传追踪表明，近一半有过 UCP1 表达史的脂肪细胞表达高水平的 FASN，而没有当前的 UCP1 表达。FACS 分离的脂肪细胞的全转录组分析证实了存在不同的合成代谢和分解代谢表型，并鉴定了已知调节脂质合成和氧化的转录途径的差异表达。令人惊讶的是，非经典基因印迹网络的父系表达基因在合成代谢表型中明显富集，这表明它们可能参与维持代谢表型的平衡。研究结果表明，代谢异质性是激活的米色/褐色脂肪细胞的一个明显特征，可能受表观遗传控制。
