Diet‐Induced Models of Obesity (DIO) in Rodents

Didier Bagnol1, Hussien A. Al‐Shamma1, Dominic Behan1, Kevin Whelan1, Andrew J. Grottick1

1 Arena Pharmaceuticals, San Diego, California
Publication Name:  Current Protocols in Neuroscience
Unit Number:  Unit 9.38
DOI:  10.1002/0471142301.ns0938s59
Online Posting Date:  April, 2012
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Abstract

Obesity results from a complex interplay between a susceptible genotype and an environment that both promotes increased caloric intake and enables sustained decreases in energy expenditure. One commonly employed approach to modeling obesity in preclinical species is the diet‐induced obese (DIO) rodent. Here, theoretical and practical considerations for producing obese rodents via dietary manipulation, and for assessing drug‐induced changes in food intake and body weight are described. Based on these considerations, a standardized protocol for diet‐induced obesity in both mouse and rat is provided and sample data from these models are also described. Curr. Protoc. Neurosci. 59:9.38.1‐9.38.13. © 2012 by John Wiley & Sons, Inc.

Keywords: high‐fat diet; cafeteria diet; food intake; DIO

     
 
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Table of Contents

  • Introduction
  • Strategic Planning
  • Basic Protocol 1: High‐Fat Diet–Induced Obesity (DIO) in Rats
  • Basic Protocol 2: High‐Fat Diet–Induced Obesity (DIO) in Mice
  • Support Protocol 1: Acute Pharmacological Manipulation in DIO Mice and Rats
  • Support Protocol 2: Chronic Pharmacological Manipulation in DIO Mice and Rats
  • Commentary
  • Literature Cited
  • Figures
  • Tables
     
 
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Materials

Basic Protocol 1: High‐Fat Diet–Induced Obesity (DIO) in Rats

  Materials
  • Male adult outbred Sprague Dawley rats (see Critical Parameters for considerations of age and group size)
  • 45% Kcal fat, purified diet (Research Diets Inc., Harlan Teklad, Dyets Inc., Bio‐Serv, TestDiet, Kliba‐Nafag AG, Altromin)
  • 10% Kcal fat, purified diet (for control low‐fat group)
  • Individual clear plastic cages (45 × 21 × 24‐cm) with sawdust bedding (Sani‐chip; Harlan Teklad)
  • Non‐drip water bottles
  • Weighing scale (range 0 to 1000 g, accurate to ±0.1 g)
  • 1000‐ml plastic beaker or bowl

Basic Protocol 2: High‐Fat Diet–Induced Obesity (DIO) in Mice

  Materials
  • Adult male inbred mice, e.g., C57Bl6 (see Critical Parameters for considerations of age and group size)
  • 60% Kcal fat, purified diet (Research Diets Inc., Harlan Teklad, Dyets Inc., Bio‐Serv, TestDiet, Kliba‐Nafag AG, Altromin)
  • 10% Kcal fat, purified diet (for control low‐fat group)
  • Non‐drip water bottles
  • Individual clear plastic cages (28 × 28 × 12‐cm) with soft bedding (e.g., corncob or sani‐chips, Harlan) and nestlets (Ancare) and/or mouse igloo (Bio‐Serv, VWR) for environmental enrichment
  • Weighing scale (range 0 to 500 g, accurate to ± 0.1 g)
  • 1000‐ml plastic beaker or bowl (receptacle used for weighing)

Support Protocol 1: Acute Pharmacological Manipulation in DIO Mice and Rats

  Materials
  • Drug compound(s)
  • Sterile distilled water, saline, or other vehicle
  • Laboratory chow (Research Diets Inc., Harlan Teklad, Dyets Inc., Bio‐Serv, TestDiet, Kliba‐Nafag AG, Altromin)
  • Flexible plastic feeding tube (ranging from 5‐ to 8‐FR/12‐ to 18‐G; ∼12‐G/8‐FR) for oral dosing in rats or flexible plastic feeding tube (ranging from 2‐ to 5‐FR/18‐ to 22‐G; ∼22‐G/2‐FR) for oral dosing in mice
  • Sterile needles 25‐ to 27‐G for i.p./s.c./i.m. dosing in rats (larger‐gauged needles can be used if either larger volumes or insoluble compounds are to be administered) or sterile needles 27‐ to 30‐G for i.p./s.c./i.m. dosing in mice (larger‐gauged needles can be used if either larger volumes or insoluble compounds are to be administered)
  • 1‐ to 3‐ml syringes
  • Animal cages with steel raised grid flooring
  • Scale
  • Ultrasonic bath or probe sonicator
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Figures

  •   FigureFigure 9.38.1 Illustration of mean growth rate in male C57Bl6/Tac mice fed a 60% high‐fat or 10% low‐fat diet for 16 weeks.
  •   FigureFigure 9.38.2 Individual body weights from a group of male C57Bl6/Tac mice fed a 60% high‐fat diet for 16 weeks.
  •   FigureFigure 9.38.3 Daily food intake in obese rats across 7 days of treatment with either vehicle, sibutramine, or an inhibitor of gastric emptying.

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Literature Cited

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