Trigonelline attenuates hepatic complications and molecular alterations in high-fat high-fructose diet-induced insulin resistance in rats

Can J Physiol Pharmacol. 2017 Apr;95(4):427-436. doi: 10.1139/cjpp-2016-0269. Epub 2016 Oct 12.

Abstract

The present study aimed to evaluate the effect of trigonelline (TRG) on the hepatic complications associated with high-fat high-fructose (HFHF) diet-induced insulin resistance (IR) in rats. IR was induced by giving a saturated fat diet and 10% fructose in drinking water to rats for 8 weeks. Insulin-resistant rats were orally treated with TRG (50 and 100 mg/kg), sitagliptin (SIT; 5 mg/kg), or a combination of TRG (50 mg/kg) and SIT (5 mg/kg) for 14 days. Liver homogenates were used for assessment of hepatic lipids, oxidative stress biomarkers, and inflammatory cytokines. Histopathological and DNA cytometry examinations were carried out for hepatic and pancreatic tissues. Hepatic tissues were examined using Fourier-transform infrared spectroscopy for assessment of any molecular changes. Results of the present study revealed that oral treatment of insulin-resistant rats with TRG or TRG in combination with SIT significantly decreased homeostatic model assessment of IR, hepatic lipids, oxidative stress biomarkers, and the inflammatory cytokines. TRG or TRG in combination with SIT ameliorated the histopathological, DNA cytometry, and molecular alterations induced by a HFHF diet. Finally, it can be concluded that TRG has beneficial effects on the hepatic complications associated with IR due to its hypoglycemic effect and antioxidant potential.

Keywords: changements moléculaires; foie; insulin resistance; liver; molecular alterations; résistance à l’insuline; sitagliptin; sitagliptine; trigonelline.

MeSH terms

  • Alkaloids / therapeutic use*
  • Animals
  • Antioxidants / therapeutic use*
  • Biomarkers / analysis
  • Blood Glucose / analysis
  • Cytokines / analysis
  • Diet, Carbohydrate Loading / adverse effects
  • Diet, High-Fat / adverse effects
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Drug Therapy, Combination
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Lipids / analysis
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Metabolic Syndrome / complications*
  • Metabolic Syndrome / etiology
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / etiology
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar
  • Sitagliptin Phosphate / therapeutic use*

Substances

  • Alkaloids
  • Antioxidants
  • Biomarkers
  • Blood Glucose
  • Cytokines
  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Lipids
  • trigonelline
  • Sitagliptin Phosphate