Sex-specific sequels of early life stress on serine/threonine kinase activity in visceral adipose tissue from obese mice
Adverse childhood experiences (ACEs) are an established independent risk factor for chronic disease development including obesity and hypertension; however, only women exposed to 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). While female MSEW mice fed a HF display exacerbated perigonadal white adipose tissue (pgWAT) expansion and a metabolic syndrome phenotype compared to controls, male MSEW mice display similar levels of adiposity compared to control counterparts but display neurogenic hypertension. Thus, this study aimed to determine a pgWAT whether there is a sex-specific serine/threonine kinase (STKA) activity 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 that regulates cellular phosphorylation signals in visceral adipose tissue and identifies possible target phosphokinases important in adipocyte hypertrophy as a result of exposure to early life stress combined with an unhealthy. Identifying functional metabolic signatures associated with early life stress is critical to elucidate the underlying molecular mechanisms behind the sex-specific obesity risk.