Evaluation of the Effects and Mechanism of L-Citrulline on Anti-obesity by Appetite Suppression in Obese/Diabetic KK-Ay Mice and High-Fat Diet Fed SD Rats

Biol Pharm Bull. 2017;40(4):524-530. doi: 10.1248/bpb.b16-01002.


L-Citrulline (L-Cit), a free amino acid from watermelon, has effects on hypertension and anti-oxidization; however, there are few reports of effects related to obesity. This study investigated the effects and mechanism of L-Cit on anti-obesity in obese/diabetic KK-Ay mice and high-fat diet fed Sprague-Dawley (SD) rats. L-Cit induced significant reduction of food intake, body weight and fat tissue mass in obese/diabetic KK-Ay mice. Moreover, blood glucose level did not change but free fatty acid level and serum insulin level were significantly decreased by treatment with L-Cit, suggesting that L-Cit improved glucose and fatty metabolism in obesity model mice. As well as obese/diabetic KK-Ay mice, there was a significant decrease in food intake and a tendency of body weight to decrease in high-fat diet fed SD rats treated with L-Cit. Also, levels of proopiomelanocortin (POMC), a food intake suppression peptide, increased in the hypothalamus. Our study suggests that L-Cit improves metabolic syndrome through decreased body weight by appetite suppression.

MeSH terms

  • Animals
  • Anti-Obesity Agents / pharmacology
  • Anti-Obesity Agents / therapeutic use*
  • Appetite Depressants / pharmacology
  • Appetite Depressants / therapeutic use*
  • Citrulline / pharmacology
  • Citrulline / therapeutic use*
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diet, High-Fat / adverse effects*
  • Drug Evaluation, Preclinical / methods
  • Eating / drug effects
  • Eating / physiology
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism
  • Male
  • Mice
  • Obesity / chemically induced
  • Obesity / drug therapy*
  • Obesity / metabolism
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley


  • Anti-Obesity Agents
  • Appetite Depressants
  • Citrulline