Combined oral contraceptive administration in female mice attenuated high-fat diet-induced obesity but not hepatic inflammation or fibrosis

Combined oral contraceptives (COC)s are the contraceptive method of choice for millions of women worldwide. In this study, we aimed to investigate the effects of COC administration, composed of 17α-ethinylestradiol (EE2) and drospirenone (DRSP), on obesity, glucose tolerance, and hepatic steatosis in female mice. Eighty-day-old <italic>Swiss</italic> female mice were fed either a standard diet (SD) or a high-fat diet (HFD) and daily received, via gavage, 0.2 mL of distilled water (CTL-SD and CTL-HFD groups) with or without COC (COC-SD and COC-HFD groups) for 65 days. COC administration attenuated body weight and adiposity gains and prevented glucose intolerance induced by HFD in COC-HFD females. These effects were accompanied by the upregulation of <italic>Prdm16</italic> and <italic>Ucp-1</italic> genes in the brown adipose tissue (BAT) of COC-HFD mice. These females also exhibited a lower hepatic steatosis score than CTL-HFD mice; however, their liver parenchyma showed an increased number of inflammatory foci, and up-regulation of the <italic>Il-1β</italic> gene. Thus, COC administration in female mice attenuated obesity development induced by HFD, possibly through modulation of BAT function, while the increased hepatic expression of the pro-inflammatory cytokine IL-1β suggests that COC exacerbated HFD-induced liver inflammation.

Key words
drospirenone; ethynylestradiol; non-alcoholic fat liver disease; oral contraceptives