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Updated: Jun 8, 2026

Determining Basal Energy Expenditure and the Capacity of Thermogenic Adipocytes to Expend Energy in Obese Mice
06:57

Determining Basal Energy Expenditure and the Capacity of Thermogenic Adipocytes to Expend Energy in Obese Mice

Published on: November 11, 2021

Y2 and Y4 receptor signaling synergistically act on energy expenditure and physical activity

Lei Zhang1, Sabrina J Riepler, Nigel Turner

  • 1Neuroscience Research Program, Garvan Institute of Medical Research, St. Vincent's Hospital, Darlinghurst NSW 2010, Sydney, Australia.

American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
|October 1, 2010
PubMed

Insights

Targeting Neuropeptide Y receptors Y2 and Y4 simultaneously offers a promising anti-obesity strategy. Dual antagonism of these receptors significantly improves body composition and energy metabolism by increasing energy expenditure and lean mass.

Area of Science:

  • Metabolic research
  • Endocrinology
  • Obesity research

Background:

  • Neuropeptide Y (NPY) receptors are key regulators of energy balance, primarily known for influencing feeding behaviors.
  • Their specific roles in energy expenditure and interactions with other energy homeostasis processes remain largely uncharacterized.

Purpose of the Study:

  • To investigate the roles of Y2 and Y4 receptors in regulating body composition and energy metabolism.
  • To explore the synergistic effects of Y2 and Y4 receptor signaling in these processes.

Main Methods:

  • Utilized a mouse model with single (Y2 or Y4) and dual (Y2 and Y4) receptor deletions.
  • Assessed body composition using dual-energy X-ray absorptiometry.
  • Measured food intake, energy expenditure, physical activity, and respiratory exchange ratio.
  • Analyzed muscle protein levels of key metabolic regulators like PGC-1α and mitochondrial complexes.

Main Results:

  • Dual deletion of Y2 and Y4 receptors led to significant reductions in adiposity and increased lean mass, exceeding effects of single deletions.
  • Body composition changes occurred independently of food intake, with notable increases in energy expenditure and physical activity in Y4(-/-) and Y2(-/-)Y4(-/-) mice.
  • Substrate utilization was impacted, indicated by decreased respiratory exchange ratio in single knockouts.
  • Synergistic effects on fat mass regulation were linked to enhanced mitochondrial oxidative capacity in double knockout mice, evidenced by increased PGC-1α and mitochondrial complex levels.

Conclusions:

  • Y2 and Y4 receptors play critical, synergistic roles in regulating body composition and energy metabolism.
  • Dual antagonism of Y2 and Y4 receptors presents a potential therapeutic avenue for combating obesity.

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