RenaSci

Chronic Feeding Studies

Blood Pressure Measurements

 

Sub-chronic or chronic feeding studies are required to evaluate fully the effects of novel antiobesity drugs on body weight and food and water intake. These feeding studies can be performed in normal rats or mice or in overweight or obese animals. Drugs can be given by a variety or routes (including sustained infusion via sc implanted osmotic minipumps) either alone or in combination to investigate whether the effects of two drugs on body weight and food intake are additive or synergistic in nature.

 

Measures normally include daily body weight and food and water intake, change in body weight per week and overall, average daily food and water intakes per week and overall and cumulative food and water intake on each day of treatment. These parameters can also be measured during drug withdrawal when it is important to show that rebound increases in body weight, above control levels, do not occur.

 

Sub-chronic and chronic feeding studies are customised to meet the requirements of each client and can include the following options :-


     •     Glucose challenge tests at key stages to assess effects of drug on glycaemic control
     •     Blood-sampling before, during and after studies to measure plasma levels of a
           variety of metabolic parameters and biomarkers
     •     Blood and tissue-sampling for pharmacokinetic analysis (out of house)
     •     Measurement of blood pressure (rats and mice)
     •     Urinary glucose excretion and faecal fat content
     •     Pancreatic insulin levels
     •     Liver total cholesterol and triglyceride levels
     •     Removal and weighing of various tissues including fat pads, muscle, stomachs
           (and stomach contents), the gastrointestinal tract, pancreas, liver and kidneys
     •     Body composition analysis 
     •     Ex vivo binding to confirm brain penetration/site of action 
     •     Necropsy and gross post mortem analysis
     •     Preparation of tissues for histology and routine immunohistochemical and
           histological staining


Examples of data obtained in chronic feeding studies are given below and on the webpages describing our various animal models and assays for evaluating novel drugs to treat obesity and diabetes.

Effect of Rimonabant or Change of Diet on Body Weight in DIO Mice

 

Effect of Rimonabant or Change of Diet on Daily Food Intake in DIO Mice

 

Effect of Rimonabant or Change of Diet on Average Food Intake on DIO Mice

 

Effect of Rimonabant or Change of Diet on Glucose Tolerance in DIO Mice

 

Please contact us for further information and to discuss your specific experimental requirements.

 

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.

 

Grempler et al. 2010. Weight Loss Induced by the Potent and Selective SGLT-2 Inhibitor, BI 10773, is Due to Body Fat Reduction Studies in Dietary-Induced Obese Rats. Abstract No. 1793-P. American Diabetes Association 70th Scientific Sessions, Orlando, Florida, 25th-29th June 2010.

 

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.

 

Reiche et al. 2011. Chronic administration of a new dual NEP/ECE inhibitor or lorsartan improves renal function in mice with diabetic nephropathy. Abstract No. 1011-P. American Diabetes Association 71st Scientific Sessions, San Diego, California, 24th-28th June 2011.

 

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.

 

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.

 

Vickers et al. 2011. The DPP-4 inhibitor linagliptin is weight neutral in the DIO rat but inhibits the weight gain of DIO animals withdrawn from exenatide. Abstract No. 979-P. American Diabetes Association 71st Scientific Sessions, San Diego, California, 24th-28th June 2011.

 

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]