Dorsomedial hypothalamic BDNF neurons integrate thermal afferent signals to control energy expenditure

Abstract

Mutations in the gene brain-derived neurotrophic factor (BDNF) cause obesity in humans. BDNF signaling and its expressing neurons in the hypothalamus help control feeding, energy expenditure (EE), and physical activity. However, whether the BDNF neurons interact with another EE-regulating system, the thermoregulation circuitry, remains unclear. Here, we show that BDNF neurons in the dorsomedial hypothalamus (DMH) are activated by environmental cooling and sufficient to induce body temperature increases and brown adipose tissue (BAT) thermogenesis. Conversely, blocking these neurons impairs BAT thermogenesis and cold defense, causing body weight gain and glucose intolerance. DMH BDNF neurons are therefore an important type of thermoregulatory neuron, integrating thermal afferent signals to control EE during cold defense. This reveals a critical intersection between the BDNF circuitry and the thermoregulatory system.

The Pleiotropic Potential of BDNF beyond Neurons: Implication for a Healthy Mind in a Healthy Body

“…While BDNF infusion into the PVH increases energy expenditure coupled with an elevation of UCP1-mediated thermogenesis [32], energy expenditure only, and not UCP1 levels, are increased when BDNF is injected into the VMH [50]. In the murine DMH, neurons expressing BDNF are quickly activated by cold temperatures, and their activation is sufficient to increase body temperature, energy expenditure and physical activity [51]. Considering that BAT thermogenesis is the main component of energy expenditure in these animals, rodents use β-oxidation of fatty acids in BAT to maintain body temperature.…”

The Pleiotropic Potential of BDNF beyond Neurons: Implication for a Healthy Mind in a Healthy Body

“…While BDNF infusion into the PVH increases energy expenditure coupled with an elevation of UCP1mediated thermogenesis [41], energy expenditure only, and not UCP1 levels, are increased when BDNF is injected into the VMH [50]. In the murine DMH, neurons expressing BDNF are quickly activated by cold temperatures, and their activation is sufficient to increase body temperature, energy expenditure and physical activity [51]. Considering that BAT thermogenesis is the main component of energy expenditure in these animals, rodents use β-oxidation of fatty acids in BAT to maintain body temperature.…”