Estrogen Signaling in the Ventromedial Hypothalamus Modulates Adipose Tissue Metabolic Adaptation

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While sexual dimorphisms have been reported in the adipose tissue’s metabolic adaptation to environmental temperature or nutritional challenges, the sex-specific mechanisms regulating adipose tissue’s responses are not fully understood. There is increasing evidence demonstrating that the female sex hormone, estrogen, plays a vital role in sex dimorphic control of adipose tissue metabolism. We and others have consistently shown that central estrogen signaling mediated by estrogen receptor α (ERα) increases sympathetic activity, promotes brown adipose tissue (BAT) thermogenesis and white adipose tissue (WAT) browning, and diminishes excessive adiposity. ERα is abundantly expressed in the ventrolateral region of the ventromedial hypothalamus (vlVMH), a sex-dimorphic structure and the only ERα site in the brain that directly modulates BAT thermogenesis. Despite the abundant evidence supporting the role of ERαvlVMH in energy expenditure and metabolic function, it is still unclear whether ERαvlVMH-originated networks respond to environmental challenges, subsequently regulating adipose tissue metabolic adaptations. Here, we aim to test whether estrogen-initiated ERαvlVMH signaling and its downstream circuit contribute to sex dimorphic regulation of adipose tissue metabolic adaptation. The first aim is to determine if ERαvlVMH sex-dimorphically modulates BAT and WAT metabolism in response to temperature or nutritional challenge. The second aim is to determine if the dorsal raphe nucleus (DRN) relays ERαvlVMH neuron signals to adipose tissue to modulate metabolic adaptation. Results from these studies will advance our current understanding of adipose tissue plasticity and adaptation in general. Further, our studies will reveal the brain ERα-originated networks that respond to temperature or nutritional challenges and initiate subsequent changes in adipose tissue metabolism.