Effect of Ursolic Acid on Insulin Resistance and Hyperinsulinemia in Rats with Diet-Induced Obesity: Role of Adipokines Expression

J Med Food. 2020 Mar;23(3):297-304. doi: 10.1089/jmf.2019.0154. Epub 2019 Nov 20.

Abstract

Excess of visceral adipose tissue (VAT) characteristic of obesity leads to a proinflammatory state disrupting the insulin signaling pathway, triggering insulin resistance (IR) and inflammation, the main processes contributing to obesity comorbidities. Ursolic acid (UA), a pentacyclic triterpenoid occurring in a variety of plant foods, exhibits anti-inflammatory properties. The aim of this study was to evaluate UA effects on IR, hyperinsulinemia, and inflammation in experimental diet-induced obesity. Forty male Wistar rats were randomly assigned to eight groups (n = 5). One group was used for time 0. Three groups were labeled as OBE (control): receiving high-fat diet (HFD; fat content 45.24% of energy) during 3, 6, or 9 weeks; three groups UA-PREV: exposed to simultaneous HFD and UA during 3, 6, or 9 weeks to evaluate UA preventive effects; one group UA-REV: receiving HFD for 6 weeks, followed by simultaneous HFD and UA for three additional weeks to analyze UA reversal effects. Measurements were performed after 3, 6, or 9 weeks of treatment. Adiposity was calculated by weighing VAT after sacrifice. Serum markers were quantified through colorimetric and enzyme-linked immunosorbent assay methods. VAT adipokines RNAm expression was evaluated by quantitative reverse transcriptase-polymerase chain reaction. Data were analyzed by Kruskal-Wallis and Mann-Whitney U tests. UA significantly decreased adiposity, IR, hyperinsulinemia, triacylglycerides, and cholesterol levels, and also VAT mRNA expression of MCP-1 (monocyte chemoattractant protein-1), IL (interleukin)-1β and IL-6, concomitantly increasing adiponectin levels. UA metabolic effects demonstrated in this study support its potential therapeutic utility to improve IR, hyperinsulinemia, and inflammation observed in obesity and diabetes.

Keywords: T2D; adiposity; dyslipidemia; nutraceutics.

MeSH terms

  • Adipokines / genetics*
  • Adipokines / metabolism
  • Animals
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Diet, High-Fat / adverse effects
  • Humans
  • Hyperinsulinism / drug therapy*
  • Hyperinsulinism / etiology
  • Hyperinsulinism / genetics
  • Hyperinsulinism / metabolism
  • Insulin Resistance*
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Male
  • Obesity / drug therapy*
  • Obesity / etiology
  • Obesity / genetics
  • Obesity / metabolism
  • Rats
  • Rats, Wistar
  • Triterpenes / administration & dosage*
  • Ursolic Acid

Substances

  • Adipokines
  • Ccl2 protein, rat
  • Chemokine CCL2
  • Interleukin-1beta
  • Interleukin-6
  • Triterpenes