Leptin signalling in the dorsal vagal complex and ventrolateral medulla with age and high-fat diet induced obesity
Purpose: The brainstem is a known contributor to central energy regulation and responds to leptin. Currently, the leptin signalling response to high-fat diet induced obesity in the brainstem is poorly understood. In this study we examined key leptin signalling markers in the Dorsal Vagal Complex (DVC) and Ventrolateral Medulla (VLM) of mice during mid-term (8 weeks) and long-term (20 weeks) high-fat diet induced obesity. Methods: C57Bl/6 male mice aged 12 weeks were fed either a high-fat (HF) or a low-fat control diet (LF), then examined after 8 or 20 weeks of feeding. Leptin signalling markers in the brainstem were examined by Western blot (n=3-8) following the intracerebroventricular injection of leptin or saline. Results: In the DVC, central leptin injection significantly increased pSTAT3 levels in the 8 week LF group (p=0.021), but not in the HF group. However, leptin administration did not increase pSTAT3 levels in either 20 week LF or HF group. In the VLM, pSTAT3 was significantly increased in the 8 week HF group compared with the LF group (p=0.038). pAMPK in the VLM decreased (p=0.023), while POMC in the DVC increased (p=0.049), in response to leptin injection in the 20 week LF group, but not in the 8 week LF group. Conclusion: Both high-fat diet and age impede leptin-pSTAT3 signalling in the DVC of the brainstem. Mid-term high-fat diet can activate pSTAT3 in the VLM. Age associated leptin-pSTAT3 deficiency in the brainstem may be compensated for by decreased pAMPK signalling and increased POMC expression in response to central leptin.