2. Academic Validation
  3. Neuregulin4 Acts on Hypothalamic ErBb4 to Excite Oxytocin Neurons and Preserve Metabolic Homeostasis

Neuregulin4 Acts on Hypothalamic ErBb4 to Excite Oxytocin Neurons and Preserve Metabolic Homeostasis

  • Adv Sci (Weinh). 2023 Apr 14;e2204824. doi: 10.1002/advs.202204824.
Yi Zhang 1,  Yangyang Zhu 1 2,  Jinghui Wang 1 3,  Li Jin 1,  Mingwei Guo 4,  Liwei Chen 1,  Lina Zhang 1,  Yangyang Li 1,  Baocheng Wan 1,  Rong Zhang 1,  Weiping Jia 1,  Cheng Hu 1 2
Affiliations

Affiliations

  • 1 Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, P. R. China.
  • 2 Institute for Metabolic Disease, Fengxian Central Hospital Affiliated to Southern Medical University, Shanghai, 201449, P. R. China.
  • 3 Department of Endocrinology, Affiliated Hospital of Nantong University, Nantong, 226001, P. R. China.
  • 4 Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, P. R. China.
PMID: 37060105 DOI: 10.1002/advs.202204824
Abstract

Neuregulin 4 (Nrg4) is an adipose tissue-enriched secreted factor that modulates glucose and lipid metabolism. Nrg4 is closely associated with obesity and preserves diet-induced metabolic disorders. However, the specific mechanisms via which Nrg4 regulates metabolic homeostasis remain incompletely understood. Here, this work finds that the Nrg4 receptor, ErbB4, is highly expressed in the hypothalamus, and the phosphorylation of hypothalamic ErbB4 is reduced in diet-induced obesity (DIO) mice. Peripheral Nrg4 can act on ErbB4 via blood circulation and excite neurons in the paraventricular nucleus of hypothalamus (PVN). Central administration of recombinant Nrg4 protein (rNrg4) reduces obesity and related metabolic disorders by influencing energy expenditure and intake. Overexpression of ErbB4 in the PVN protects against obesity, whereas its knock down in oxytocin (Oxt) neuron accelerates obesity. Furthermore, Nrg4-ErbB4 signaling excites Oxt release, and ablation of Oxt neuron considerably attenuates the effect of Nrg4 on energy balance. These data suggest that the hypothalamus is a key target of Nrg4, which partially explains the multifaceted roles of Nrg4 in metabolism.

Keywords

ErbB4; hypothalamus; neuregulin4; obesity; oxytocin neuron.

Figures
Products