Preventive and ameliorating effects of citrus D-limonene on dyslipidemia and hyperglycemia in mice with high-fat diet-induced obesity

Eur J Pharmacol. 2013 Sep 5;715(1-3):46-55. doi: 10.1016/j.ejphar.2013.06.022. Epub 2013 Jul 6.


D-limonene is a major constituent in citrus essential oil, which is used in various foods as a flavoring agent. Recently, d-limonene has been reported to alleviate fatty liver induced by a high-fat diet. Here we determined the preventive and therapeutic effects of d-limonene on metabolic disorders in mice with high-fat diet-induced obesity. In the preventive treatment, d-limonene decreased the size of white and brown adipocytes, lowered serum triglyceride (TG) and fasting blood glucose levels, and prevented liver lipid accumulations in high-fat diet-fed C57BL/6 mice. In the therapeutic treatment, d-limonene reduced serum TG, low-density lipoprotein cholesterol (LDL-c) and fasting blood glucose levels and glucose tolerance, and increased serum high-density lipoprotein cholesterol (HDL-c) in obese mice. Using a reporter assay and gene expression analysis, we found that d-limonene activated peroxisome proliferator-activated receptor (PPAR)-α signaling, and inhibited liver X receptor (LXR)-β signaling. Our data suggest that the intake of d-limonene may benefit patients with dyslipidemia and hyperglycemia and is a potential dietary supplement for preventing and ameliorating metabolic disorders.

Keywords: Dyslipidemia; Hyperglycemia; Metabolic disorder; d-limonene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects
  • Adipocytes / pathology
  • Animals
  • Body Weight / drug effects
  • Cell Differentiation / drug effects
  • Cell Size / drug effects
  • Citrus / chemistry*
  • Cyclohexenes / pharmacology*
  • Diet, High-Fat / adverse effects*
  • Dietary Supplements
  • Dyslipidemias / diet therapy
  • Dyslipidemias / prevention & control*
  • Female
  • Gene Expression Regulation / drug effects
  • Glucose / metabolism
  • Hyperglycemia / complications*
  • Hyperglycemia / diet therapy
  • Hyperglycemia / prevention & control*
  • Limonene
  • Lipids / blood
  • Liver / drug effects
  • Liver / pathology
  • Liver X Receptors
  • Mice
  • Mice, Inbred C57BL
  • Obesity / blood
  • Obesity / complications*
  • Obesity / etiology
  • Obesity / pathology
  • Orphan Nuclear Receptors / metabolism
  • PPAR alpha / metabolism
  • Signal Transduction / drug effects
  • Terpenes / pharmacology*


  • Cyclohexenes
  • Lipids
  • Liver X Receptors
  • Orphan Nuclear Receptors
  • PPAR alpha
  • Terpenes
  • Limonene
  • Glucose