Mechanic Insight into the Distinct and Common Roles of Ovariectomy Versus Adrenalectomy on Adipose Tissue Remodeling in Female Mice

Abstract

Dysfunctions of the ovaries and adrenal glands are both evidenced to cause aberrant adipose tissue (AT) remodeling and resultant metabolic disorders, but their distinct and common roles are poorly understood. In this study, through biochemical, histological and RNA-seq analyses, we comprehensively explored the mechanisms underpinning subcutaneous (SAT) and visceral adipose tissue (VAT) remodeling, in response to ovariectomy (OVX) versus adrenalectomy (ADX) in female mice. OVX promoted adipocyte differentiation and fat accumulation in both SAT and VAT, by potentiating the Pparg signaling, while ADX universally prevented the cell proliferation and extracellular matrix organization in both SAT and VAT, likely by inactivating the Nr3c1 signaling, thus causing lipoatrophy in females. ADX, but not OVX, exerted great effects on the intrinsic difference between SAT and VAT. Specifically, ADX reversed a large cluster of genes differentially expressed between SAT and VAT, by activating 12 key transcription factors, and thereby caused senescent cell accumulation, massive B cell infiltration and the development of selective inflammatory response in SAT. Commonly, both OVX and ADX enhance circadian rhythmicity in VAT, and impair cell proliferation, neurogenesis, tissue morphogenesis, as well as extracellular matrix organization in SAT, thus causing dysfunction of adipose tissues and concomitant metabolic disorders.

Adrenarche-accompanied rise of adrenal sex steroid precursors prevents NAFLD in Young Female rats by converting into active androgens and inactivating hepatic Srebf1 signaling

“…The resulting P -values were adjusted using the Benjamini and Hochberg’s approach for controlling the false discovery rate. Genes with an adjusted P value (q value) < 0.05 were assigned as differentially expressed (DEGs) [ 41 ]. Hierarchical cluster analysis was conducted to assemble genes with similar expression patterns across groups using Cluster 3.0 software.…”

Hepatic-Specific FGF21 Knockout Abrogates Ovariectomy-Induced Obesity by Reversing Corticosterone Production

“…Serum FGF21 (MF2100; R&D Systems, Minneapolis, MN, USA), FSH (CSB-E06871m; CUSABIO, Houston, TX, USA), corticosterone (KGE009; R&D Systems, Minneapolis, MN, USA) and insulin (80-INSHU-CH01; ALPCO, Salem, NH, USA) concentrations were determined with commercial ELISA kits, according to the manufacturer's instruction. Serum-free fat acid (FFA) and triglyceride (TG) levels were measured via a nonesterified free fatty acids assay kit (A042-2-1) and triglyceride assay Kit (A110-1-1) from Nanjing Jiancheng Bioengineering Institute (Nanjing, China), as our previous descriptions [32]. The liver tissue of mice was added with nine times the amount of saline to prepare 10% tissue homogenization in the ice water bath, and TG levels in the liver tissue of mice were measured using the enzymic method according to the kit instructions.…”