RenaSci

Dietary-induced Obese Animals

Dietary-induced Obese Mouse

 

Dietary-induced obese (DIO) mice and rats are well-established animal models of obesity.

 

Obesity is induced in male C57BL/6J mice by allowing them unlimited access to high fat diet supplying either 45% or 60% energy as fat or in female Wistar rats by allowing them free access to a simplified cafeteria diet consisting of high-fat chow, ground chocolate and ground peanuts to mirror a typical calorie-dense Western diet. Obesity is induced in both rats and mice over a 3-4 month period.

 

Key features of our dietary-induced obese rat and mouse models are : -

 

     •     Weight-stable (allowing weight-loss as opposed to reduced weight gain to be
           measured)
     •     Marked visceral adiposity (30-35% fat)
     •     High leptin levels
     •     Moderate insulin resistance (rather than overt diabetes)
     •     Mild lipid abnormalities
     •     Polygenic basis

 

Studies in dietary-induced obese mice are popular as an initial screen as they require less compound than dietary-induced obese rats and are easier to perform as mice are given their food as a single-source. Body composition can be determined throughout studies in dietary-indiced obese mice using DEXA (Dual-Energy X-Ray Absorptiometry). 

 

Weight-loss Produced by Reference Compounds in DIO Mice

 

Effect of Rimonabant on Food intake in DIO Mice

 

Dietary-induced obese rats and mice display similar symptoms to those observed in common human obesity (face validity) and the factors contributing to the initiation and maintenance of obesity are similar in animals and man (construct validity). Dietary-indiced obese animals have excellent predictive validity as both centrally- and peripherally-acting drugs producing weight-loss in man (eg sibutramine, orlistat and rimonabant) reduce body weight in DIO rats and mice.

Effect of Drugs on Body Weight and Food Intake in Dietary-induced Obese Rats

 

The magnitude of weight-loss produced by a variety of different drugs in dietary-induced obese, female Wistar rats correlates highly with the weight-loss produced in the clinic. The model is therefore considered to be the 'gold standard' model for predicting the efficacy of novel antiobesity drugs in man. However, as the rats are given three different types of food to encourage them to eat the model is more labour-intensive and therefore more expensive than studies in dietary-induced obese mice. Dietary-induced obese, female Wistar rats are typically used to test compounds in development rather than as an initial screen of antiobesity action. 

 

Acute, sub-chronic and chronic feeding studies can be performed in DIO mice and rats and drugs can be given by a variety of routes including infusion from sc implanted osmotic minipumps. Body weights and daily food and water intakes are recorded routinely. Studies in dietary-induced obese rats and mice can include a number of other optional extras to investigate the effects of drugs on obesity-related comorbidities (critical clinical outcomes when evaluating the benefits of new drugs for weight management) or to investigate the mechanisms underlying the weight-loss. For example :-

 

     •     Glucose tolerance tests before, during and at the end of treatment
     •     Plasma analysis of a variety of metabolic parameters
     •     Blood pressure measurements
     •     Fat pad weights
     •     Body composition analysis
     •     Faecal fat analysis
     •     Urinary glucose excretion
     •     Gastric emptying (weights of stomachs, stomach contents and gastrointestinal
            tract)
     •     Blood and tissue-sampling for pharmacokinetic analysis
     •     Necropsy and post mortem analysis
     •     Histopathology and Immunohistochemistry

 

All studies in dietary-induced obese mice and rats are customised to meet the specific requirements of each client and include advice on experimental design, statistical analysis by a qualified statistician, fully audited data pack and written reports to regulatory standards if required.

 

Please contact us for further information about our animal models of dietary-induced obesity or to enquire about the supply of dietary-induced obese rats and mice for your own studies.

 

Posters

 

Cheetham et al. 2008. Effect of the MCH1 antagonist, GW803430, on body weight, food and water intake, glucose tolerance, fat pad weight, ex vivo binding and various plasma parameters in dietary-induced obese C57BL/6J mice. Program No. 584.24. Society for Neuroscience Meeting, Washington, DC, 15th-19th November 2008.

 

Jackson et al. 2004. Comparison of the effects of sibutramine and orlistat on body weight, food and water intake and body composition in dietary-induced obese rats.  Program No. 76.19. Society for Neuroscience Meeting, San Diego, California, 23rd-27th October 2004. 

 

Jackson et al. 2005. Comparison of the effects of rimonabant and sibutramine in a rat model of dietary induced obesity. Program No. 532.13. Society for Neuroscience Meeting, Washington, DC, 12th-16th November 2005.

 

Jackson et al. 2007. Effect of chronic administration of topiramate and phentermine alone and in combination in an animal model of dietary induced obesity. Program No. 629.15. Society for Neuroscience Meeting, San Diego, California, 3rd-7th November 2007.

 

Shacham et al. 2006. PRX-07034, a potent and selective 5-HT6 receptor antagonist, reduces food intake and body weight in dietary-induced obese rats. Program No. 62.10. Society for Neuroscience Meeting, Atlanta, Georgia, 14th-18th October, 2006.

 

Surman et al. 2011. ALB-127158(a): An MCH1 receptor antagonist that exhibits weight loss and improvements in insulin sensitivity in diet-induced obese mice. Abstract No. 0108-LB. American Diabetes Association 71st Scientific Sessions, San Diego, California, 24th-28th June 2011.

 

Vickers et al. 2005. Comparison of the effects of rimonabant, sibutramine and orlistat on acute food intake and in a model of dietary induced obesity in the mouse. Program No. 532.12. Society for Neuroscience Meeting, Washington, DC, 12th-16th November 2005.

 

Manuscripts

 

Cheetham and Jackson 2012. Rodent models to evaluate anti-obesity drugs. In: TRP Channel Targets for Drugs and Toxins, Volume II. A Szallasi and T Bíró (Eds), Methods in Pharmacology and Toxicology, Volume I, Springer Protocols, Humana Press, pp351-376.

 

Vickers et al. 2011. The utility of animal models to evaluate novel anti-obesity agents. Br J Pharmacol 164: 1248-1262. [PubMed]

 

Vickers et al. 2014. Combination of the sodium-glucose cotransporter-2 inhibitor empagliflozin with orlistat or sibutramine further improves the body weight reduction and glucose homeostasis of obese rats fed a cafeteria diet. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 7: 265-275. [PubMed]