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Gastric inhibitory polypeptide receptor antagonist, SKL-14959, suppressed body weight gain on diet-induced obesity

T Nakamura1, H Tanimoto1, Y Mizuno2

  • 1Biological Research Group, Drug Discovery Laboratories Sanwa Kagaku Kenkyusho Inabe-city Mie Japan.

Obesity Science & Practice
|April 20, 2018
PubMed
Abstract

Insights

The gastric inhibitory polypeptide receptor antagonist, SKL-14959, effectively reduced weight gain in obese mice by inhibiting lipid uptake and improving lipid metabolism. This compound offers a potential therapeutic strategy for combating obesity.

Area of Science:

  • Metabolic Research
  • Pharmacology

Background:

  • Gastric inhibitory polypeptide is crucial for glucose and lipid metabolism, with its dysregulation linked to obesity and insulin resistance.
  • Understanding the role of gastric inhibitory polypeptide signaling in metabolic disorders is essential for developing targeted therapies.

Purpose of the Study:

  • To investigate the anti-obesity effects of SKL-14959, a gastric inhibitory polypeptide receptor antagonist.
  • To evaluate the impact of SKL-14959 on diet-induced obesity in a mouse model.

Main Methods:

  • Diet-induced obese mice were treated with SKL-14959 for 96 days, with body weight and food intake monitored.
  • Physiological, biochemical, histochemical, and gene expression analyses were performed.
  • Lipid uptake was assessed using a 14C-oleic acid challenge.

Main Results:

  • SKL-14959 significantly suppressed weight gain without affecting food intake.
  • The compound decreased liver and muscle triacylglycerol content and improved liver lipid staining.
  • SKL-14959 modulated key genes involved in lipid metabolism in the liver and inhibited adipose tissue lipid uptake.

Conclusions:

  • SKL-14959 demonstrates anti-obesity effects by inhibiting lipid uptake and enhancing lipid metabolism.
  • These findings suggest SKL-14959 as a potential therapeutic agent for managing obesity.
Keywords:
GIPGIP receptor antagonistanti‐obesityfatty liver

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