Division of Nutritional Sciences, College of Agriculture and Life Sciences, Cornell University, Ithaca, New York, NY, USA.
Dell Pediatric Research Institute, Departments of Chemistry, Pediatrics, and Nutrition, Dell Medical School and the College of Natural Sciences, University of Texas at Austin, Austin, TX, USA.
Commun Biol. 2022 Jun 14;5(1):584. doi: 10.1038/s42003-022-03531-5.
Beige adipocytes are induced by cold temperatures or β3-adrenergic receptor (Adrb3) agonists. They create heat through glucose and fatty acid (FA) oxidation, conferring metabolic benefits. The distinct and shared mechanisms by which these treatments induce beiging are unknown. Here, we perform single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq) on adipose tissue from mice exposed to cold or an Adrb3 agonist to identify cellular and chromatin accessibility dynamics during beiging. Both stimuli induce chromatin remodeling that influence vascularization and inflammation in adipose. Beige adipocytes from cold-exposed mice have increased accessibility at genes regulating glycolytic processes, whereas Adrb3 activation increases cAMP responses. While both thermogenic stimuli increase accessibility at genes regulating thermogenesis, lipogenesis, and beige adipocyte development, the kinetics and magnitudes of the changes are distinct for the stimuli. Accessibility changes at lipogenic genes are linked to functional changes in lipid composition of adipose. Both stimuli tend to decrease the proportion of palmitic acids, a saturated FA in adipose. However, Adrb3 activation increases the proportion of monounsaturated FAs, whereas cold increases the proportion of polyunsaturated FAs. These findings reveal common and distinct mechanisms of cold and Adrb3 induced beige adipocyte biogenesis, and identify unique functional consequences of manipulating these pathways in vivo.
米色脂肪细胞可由冷刺激或β3 肾上腺素能受体（Adrb3）激动剂诱导产生。它们通过葡萄糖和脂肪酸（FA）氧化产热，带来代谢益处。这些治疗方法诱导米色形成的独特和共同机制尚不清楚。在这里，我们对暴露于冷或 Adrb3 激动剂的小鼠脂肪组织进行转座酶可及染色质测序（snATAC-seq）的单细胞分析，以鉴定米色形成过程中的细胞和染色质可及性动态变化。两种刺激均诱导影响脂肪血管生成和炎症的染色质重塑。暴露于冷刺激的米色脂肪细胞中，调节糖酵解过程的基因的可及性增加，而 Adrb3 激活增加 cAMP 反应。虽然两种生热刺激都增加了调节产热、脂肪生成和米色脂肪细胞发育的基因的可及性，但刺激的动力学和幅度是不同的。脂肪生成基因的可及性变化与脂肪中脂质组成的功能变化相关。两种刺激都倾向于降低棕榈酸（一种脂肪中的饱和 FA）的比例。然而，Adrb3 激活增加了单不饱和脂肪酸的比例，而冷刺激则增加了多不饱和脂肪酸的比例。这些发现揭示了冷和 Adrb3 诱导米色脂肪细胞生成的共同和独特机制，并确定了体内操纵这些途径的独特功能后果。
