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Control of Eating Behavior Using a Novel Feedback System
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A hypothalamic pathway for Augmentor α-controlled body weight regulation.

Mansoor Ahmed1, Navjot Kaur2, Qianni Cheng1

  • 1Department of Pharmacology, Yale School of Medicine, New Haven, CT 06520.

Proceedings of the National Academy of Sciences of the United States of America
|April 12, 2022
PubMed
Summary

Augmentor ligands Augα and Augβ regulate body weight. Mice lacking Augα show leanness and increased activity, suggesting a role in energy homeostasis and potential therapeutic targets for metabolic diseases and cancer.

Keywords:
cell signalingenergy expendituremetabolismphosphorylationsurface receptors

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Area of Science:

  • Endocrinology
  • Neuroscience
  • Molecular Biology

Background:

  • Augmentor α (Augα) and Augmentor β (Augβ) are novel ligands for receptor tyrosine kinases Alk and Ltk.
  • While oncogenic Alk mutations drive cancer, the physiological functions of Augα and Augβ remain unclear.

Purpose of the Study:

  • To investigate the physiological roles of Augα and Augβ in vivo.
  • To explore the connection between Alk signaling, energy homeostasis, and cancer.

Main Methods:

  • Generation and analysis of mice deficient in Augα and/or Augβ.
  • Metabolic phenotyping, including assessment of body weight and physical activity.
  • Investigation of Augα expression and regulation in AgRP neurons and the paraventricular nucleus (PVN).

Main Results:

  • Augα deficiency, alone or with Augβ deficiency, results in a lean phenotype and resistance to diet-induced obesity.
  • Augα-deficient mice exhibit increased physical activity.
  • Augα is expressed in and metabolically regulated by Agouti-related peptide (AgRP) neurons, influencing the paraventricular nucleus (PVN).

Conclusions:

  • Augα plays a significant role in regulating body weight and energy expenditure.
  • Alk signaling, through Augα and AgRP neurons, represents a conserved pathway for controlling body weight.
  • This pathway's co-option in Alk-driven cancers suggests therapeutic potential for metabolic diseases and cancer.