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Mice lacking δ-opioid receptors resist the development of diet-induced obesity

Traci A Czyzyk1, Amparo Romero-Picó, John Pintar

  • 1Obesity Research, Lilly Research Laboratories, Indianapolis, Indiana, USA.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|May 18, 2012
PubMed

Insights

Mice lacking the delta-opioid receptor (DOR) showed reduced weight gain and fat mass, despite increased food intake. This suggests DOR plays a key role in regulating energy expenditure and obesity.

Area of Science:

  • Endocrinology
  • Metabolism
  • Neuroscience

Background:

  • Opioid receptor signaling influences feeding behavior, but subtype-specific roles in energy balance are unclear.
  • Understanding the delta-opioid receptor (DOR) contribution to energy homeostasis is crucial for metabolic research.

Purpose of the Study:

  • To investigate the role of genetic disruption of the delta-opioid receptor (DOR) in controlling energy homeostasis.
  • To determine the impact of DOR deficiency on weight gain, fat mass, and energy expenditure.

Main Methods:

  • Comparison of wild-type and DOR-knockout mice fed standard and high-energy diets.
  • In vivo indirect calorimetry to assess energy expenditure.
  • Real-time PCR and Western blot analysis of key thermogenic markers in tissues.

Main Results:

  • DOR-knockout mice exhibited significantly reduced weight gain and fat mass compared to controls on a high-energy diet.
  • Despite hyperphagia, DOR-knockout mice displayed increased energy expenditure due to enhanced brown adipose tissue thermogenesis.
  • Upregulation of UCP1, PGC1α, and FGF21 was observed, alongside reduced hepatic triglyceride content in DOR-deficient mice.

Conclusions:

  • Delta-opioid receptor (DOR) deficiency enhances thermogenic pathways and energy expenditure, offering a novel therapeutic target for obesity.
  • DOR plays a significant role in regulating energy balance and mitigating diet-induced metabolic dysfunction.

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