Steady-state energy balance in animal models of obesity and weight loss

Abstract

Objective: We wanted to exam the steady-state energy balance by using high-fat diet-induced obese (DIO) rats and mice as models for positive energy balance, and gastric bypassed (GB) rats and gene knockout of muscarinic acetylcholine M3 receptor (M3KO) mice as models for negative energy balance.

Methods: One hundred and thirty-two rats and mice were used. Energy balance was measured by a comprehensive laboratory animal monitoring system. Gene expression was analysed by in situ hybridisation in M3KO mice.

Results: DIO rats reached the plateau of body weight 28 weeks after starting high-fat diet (25% heavier than controls), whereas DIO mice reached the plateau after 6 weeks (23% heavier than controls). At the plateau, DIO rats had higher calorie intake during the light phase but not during the dark phase, while mice had the same calorie intake per day as controls. DIO rats and mice had lower energy expenditure (EE) and respiratory exchange ratio (RER) than controls. GB-rats reached the plateau (15% weight loss) 2 weeks after surgery and had the same calorie intake as sham-operated controls. EE, but not RER, was higher in GB rats than controls during the dark phase. The lean M3KO mice (25% lighter than wild-type (WT) mice at the plateau between 6 and 15 months of age) had the same calorie intake but higher EE, RER and hypothalamic mRNA expression of NPY, AgRP and leptin receptor than WT mice.

Conclusion: When body weight gain or loss reached a plateau, the steady-state energy balance was mainly maintained by EE and/or RER rather than calorie intake.

Keywords:

• Eating behaviour
• high-fat diet
• gastric bypass
• muscarinic acetylcholine M3 receptor knockout
• mice
• rats

Disclosure of interest

No conflicts of interest, financial or otherwise, are declared by the authors.

Additional information

Funding

This work was supported by European Union Seventh Framework Programme (Full4Health), the Joint Programme of the Medical Faculty of Norwegian University of Science and Technology (NTNU) and St. Olav’s University Hospital, the Liaison Committee between the Central Norway Regional Health Authority and NTNU.