Estrogenic re-mapping of the metabolic response to an energy deficit

ABSTRACT During menopause, estrogen levels decline, and this decline is accompanied by a myriad of metabolic changes, including decreased energy expenditure. The signaling mechanisms underlying the effects of estrogen on energy expenditure remain incompletely understood, however. In response to energy deficit, mice have evolved the ability to drastically reduce their energy expenditure by entering a hypothermic and hypometabolic state known as torpor. From my preliminary research, it has been shown that circulating estrogens reduce fasting-induced torpor usage, keeping energy expenditure high even in the face of a dangerous energy deficit. The proposed research seeks to understand the signaling mechanisms underlying this estrogenic remapping of the metabolic response to an energy deficit through two major aims. 1) Test whether circulating estrogens reduce torpor usage by acting on the medial preoptic area of the hypothalamus, a brain region that is sensitive to circulating estrogens and is known to coordinate torpor in mice, making it an ideal candidate. 2) Test whether circulating estrogens alter the activity of neurons in the medial preoptic area of the hypothalamus, directly or indirectly, which could represent a critical cellular mechanism underlying the effects of circulating estrogens on torpor. Together, these studies will advance our understanding of how estrogen influences metabolic pathways in mice, an important step towards understanding, and eventually treating, the metabolic changes that occur during menopause. Project Number: 1F99AG095119-01 | Fiscal Year: 2025 | NIH Institute/Center: National Institute on Aging (NIA) | Principal Investigator: Paul Vander | Institution: UNIVERSITY OF CALIFORNIA LOS ANGELES, LOS ANGELES, CA | Award Amount: $43,728 | Activity Code: F99 | Study Section: Special Emphasis Panel[ZAG1 ZIJ-C (M1)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11219474