AMPKα2 in Kiss1 Neurons Is Required for Reproductive Adaptations to Acute Metabolic Challenges in Adult Female Mice

A temporary and reversible inhibition of the hypothalamo-pituitary-gonadal axis is adaptive when energy reserves are diminished, allowing individual survival and energy accumulation for eventual reproduction. The AMP-activated protein kinase (AMPK) works as a cellular sensor of the AMP to ATP ratio and ultimately of energy availability. Activation of AMPK suppresses ATP-consuming processes and stimulates ATP-producing pathways. The AMPK α2 catalytic subunit is expressed in multiple hypothalamic nuclei including those associated with reproductive control, ie, the anteroventral periventricular nucleus and the arcuate nucleus. Subsets of kisspeptin neurons in the anteroventral periventricular nucleus (20% in females) and arcuate nucleus (45% in males and 65% in females) coexpress AMPKα2 mRNA. Using the Cre-loxP approach, we assessed whether AMPKα2 in Kiss1 cells is required for body weight and reproductive function. The AMPKα2-deleted mice show no difference in body weight and time for sexual maturation compared with controls. Males and females are fertile and have normal litter size. The AMPKα2-deleted and control females have similar estradiol feedback responses and show no difference in Kiss1 mRNA expression after ovariectomy or ovariectomy plus estradiol replacement. In males, acute fasting decreased Kiss1 mRNA expression in both groups, but no effect was observed in females. However, after an acute fasting, control mice displayed prolonged diestrous phase, but AMPKα2-deleted females showed no disruption of estrous cycles. Our findings demonstrate that the AMPKα2 catalytic subunit in Kiss1 cells is dispensable for body weight and reproductive function in mice but is necessary for the reproductive adaptations to conditions of acute metabolic distress.