Leachman Jacqueline, Creeden Justin, Turner Meghan, Ahmed Nermin, Dalmasso Carolina, Loria Analia S
Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington KY 405362.
The Department of Neurosciences at the University of Toledo Medical Center.
bioRxiv. 2024 Apr 4:2024.04.03.587852. doi: 10.1101/2024.04.03.587852.
Adverse childhood experiences (ACEs) are an established independent risk factor for chronic disease including obesity and hypertension; however, only women exposed to multiple ACEs show a positive relationship with BMI. Our lab has reported that maternal separation and early weaning (MSEW), a mouse model of early life stress, induces sex-specific mechanisms underlying greater blood pressure response to a chronic high fat diet (HF). Specifically, female MSEW mice fed a HF display exacerbated perigonadal white adipose tissue (pgWAT) expansion and a metabolic syndrome-like phenotype compared to control counterparts, whereas hypertension is caused by sympathoactivation in male MSEW mice. Thus, this study aimed to determine whether there is a sex-specific serine/threonine kinase (STKA) activity in pgWAT adipose tissue associated with early life stress. Frozen pgWAT was collected from MSEW and control, male and female mice fed a HF to assess STKA activity using the Pamstation12 instrument. Overall, MSEW induces significant reduction of 7 phosphokinases (|Z| >=1.5) in females (QIK, MLK, PKCH, MST, STE7, PEK, FRAY) and 5 in males (AKT, SGK, P38, MARK, CDK), while 15 were downregulated in both sexes (DMPK, PKA, PKG, RSK, PLK, DYRK, NMO, CAMK1, JNK, PAKA, RAD53, ERK, PAKB, PKD, PIM, AMPK). This data provides new insights into the sex-specific dysregulation of the molecular network controlling cellular phosphorylation signals in visceral adipose tissue and identifies possible target phosphokinases implicated in adipocyte hypertrophy as a result of exposure to early life stress. Identifying functional metabolic signatures is critical to elucidate the underlying molecular mechanisms behind the sex-specific obesity risk associated with early life stress.
童年不良经历（ACEs）是包括肥胖和高血压在内的慢性疾病已确定的独立风险因素；然而，只有暴露于多种ACEs的女性与体重指数（BMI）呈正相关。我们实验室报告称，母婴分离和早期断奶（MSEW），一种早期生活应激的小鼠模型，会诱导对慢性高脂饮食（HF）产生更大血压反应的性别特异性机制。具体而言，与对照小鼠相比，喂食HF的雌性MSEW小鼠表现出加剧的性腺周围白色脂肪组织（pgWAT）扩张和代谢综合征样表型，而雄性MSEW小鼠的高血压是由交感神经激活引起的。因此，本研究旨在确定pgWAT脂肪组织中是否存在与早期生活应激相关的性别特异性丝氨酸/苏氨酸激酶（STKA）活性。从喂食HF的MSEW和对照雄性和雌性小鼠中收集冷冻的pgWAT，使用Pamstation12仪器评估STKA活性。总体而言，MSEW导致雌性小鼠中有7种磷酸激酶显著减少（|Z| >=1.5）（QIK、MLK、PKCH、MST、STE7、PEK、FRAY），雄性小鼠中有5种（AKT、SGK、P38、MARK、CDK），而有15种在两性中均下调（DMPK、PKA、PKG、RSK、PLK、DYRK、NMO、CAMK1、JNK、PAKA、RAD53、ERK、PAKB、PKD、PIM、AMPK）。这些数据为控制内脏脂肪组织中细胞磷酸化信号的分子网络的性别特异性失调提供了新见解，并确定了可能因暴露于早期生活应激而与脂肪细胞肥大有关的靶磷酸激酶。识别功能性代谢特征对于阐明与早期生活应激相关的性别特异性肥胖风险背后的潜在分子机制至关重要。
