Body weight reduction by increased weight loading in mice is associated with sensory signaling in the dorsal horn of the lumbar spinal cord

Abstract

Previously, we demonstrated that increased weight loading suppresses body weight and food intake in rodents. Our earlier studies suggested that the hind limbs sense this increased load and transmit signals to the Nucleus of the Solitary Tract (NTS) in the brainstem. However, the pathway of this signal transmission was unclear. To investigate if sensory neurons contribute to this signaling, mice were implanted subcutaneously with two capsules weighing ∼15 % (Load) or ∼2.5 % (Control) of their body weight in total. Five days post-implantation, neuronal activation was measured by FosB immunoreactivity. An increase of FosB expression was found in Load mice compared to Control specifically at the lumbar L3-L5 segments in the superficial laminae (I-III) of the dorsal horn (DH). These segments receive input via sensory nerves from deeper parts of the hind limbs. Intrathecal injection of the drug capsaicin, blocking sensory nerve signaling, at L3-L5 attenuated Load-induced FosB expression at the lumbar L3-L5 segments and body weight reduction. In summary, increased weight loading increases FosB expression at segments L3-L5 of the DH and reduces body weight via sensory nerves. We propose that increased weight loading enhances compression of weight-bearing bones in the hind limbs, resulting in sensory nerve transmission to cell bodies in L3-L5, which in turn reduces food intake and body weight.

Keywords: Capsaicin; Gravitostat; Obesity; Spinal cord; TRPV1.