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

The National Institute on Aging awarded $214,140 to the University of California, Los Angeles on March 18, 2026, under the Aging Research program (CFDA 93.866) to conduct research on estrogenic signaling mechanisms that regulate metabolic response to energy deficit.

The research aims to understand how circulating estrogens reduce fasting-induced torpor usage in mice, thereby maintaining high energy expenditure despite dangerous energy deficits—findings relevant to metabolic changes during menopause. The project pursues two specific objectives: testing whether circulating estrogens reduce torpor usage by acting on the medial preoptic area of the hypothalamus, and testing whether circulating estrogens alter the activity of neurons in that hypothalamic region. The studies advance understanding of estrogen's influence on metabolic pathways as a foundation for understanding and treating metabolic changes occurring during menopause.

UCLA's Office of Research Administration serves as the recipient. The period of performance extends from the award date through September 25, 2027, with work performed in California.

Abstract

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.