ABSTRACT
In this review, we provide a brief synopsis of the connections between adipose tissue and metabolic health and highlight some recent developments in understanding and exploiting adipocyte biology. Adipose tissue plays critical roles in the regulation of systemic glucose and lipid metabolism and secretes bioactive molecules possessing endocrine, paracrine, and autocrine functions. Dysfunctional adipose tissue has a detrimental impact on metabolic health and is intimately involved in key aspects of metabolic diseases such as insulin resistance, lipid overload, inflammation, and organelle stress. Differences in the distribution of fat depots and adipose characteristics relate to divergent degrees of metabolic dysfunction found in metabolically healthy and unhealthy obese individuals. Thermogenic adipocytes increase energy expenditure via mitochondrial uncoupling or adenosine triphosphate-consuming futile substrate cycles, while functioning as a metabolic sink and participating in crosstalk with other metabolic organs. Manipulation of adipose tissue provides a wealth of opportunities to intervene and combat the progression of associated metabolic diseases. We discuss current treatment modalities for obesity including incretin hormone analogs and touch upon emerging strategies with therapeutic potential including exosome-based therapy, pharmacological activation of brown and beige adipocyte thermogenesis, and administration or inhibition of adipocyte-derived factors.
ABSTRACT
Endocrine-disrupting chemicals (EDCs) are exogenous substances that alter the structure or function of the endocrine system. 4-Tert-octylphenol (OP) is one of the most representative EDCs and has estrogenic effects. In this study, we examined the effects of ethinyl estradiol (EE) and OP on the pituitary gland, placenta, and uterus of pregnant rats. Expression levels of human chorionic gonadotropin (hCG), oxytocin (OT), and contraction-associated proteins (CAPs) were determined, and uterine contractile activity was measured by uterine contraction assay. EE and OP both increased mRNA expression of OT and hCG in the pituitary gland but not the placenta. Since OT and hCG control uterine contraction, we next examined CAP expression in the uterus. Expression of 15-hydroxyprostaglandin-dehydrogenase (PGDH) was upregulated by OP, whereas expression of other CAPs was unaffected. To clarify the effect of OP on uterine contraction in pregnant rats, uterine contraction assay was performed. The 17beta-Estradiol (E2) did not affect contraction of primary uterine cells harvested from pregnant rats in a 3D collagen gel model. However, OP showed different effects from E2 by significantly reducing contraction activity. In summary, we demonstrated that OP interferes with regulation of OT and hCG in the pituitary gland as well as PGDH in the uterus, thereby reducing uterine contraction activity. This result differs from the action of endogenous E2. Collectively, these findings suggest that exposure to EDCs such as OP during pregnancycan reduce uterine contractile ability, which may result in contraction-associated adverse effects such as metratonia, bradytocia, and uterine leiomyomata.