An age-dependent alteration of the respiratory exchange ratio in the db/db mouse
Laboratory Animal Research volume 31, pages 1–6 (2015)
The leptin receptor-deficient db/db mouse is a rodent model of type 2 diabetes and obesity. Diabetes in db/db mice shows an age-dependent progression, with early insulin resistance followed by an insulin secretory defect resulting in profound hyperglycemia. However, there is insufficient data on age-dependent changes of energy metabolism in db/db mice. We demonstrated an age-dependent decrease in the respiratory exchange ratio (RER), calculated by a ratio of VO2/VCO2, in db/db mice. The RER determined by indirect calorimetry, was 1.03 in db/db mice under 6 weeks of age, which were similar to those in heterozygote (db/+) and wild-type (+/+) mice. However, RER decreased from approximately 0.9 to 0.8 by 10 weeks of age and subsequently returned to approximately 0.9 at 22 weeks of age. The changes in RER were concurrent with the alterations in body weight and blood glucose level. However, other metabolic indicators such as glucose tolerance, changes in body fat mass, and urinary glucose levels, did not change with age. The results suggested that the energy source utilized in db/db mice changed with the age-related progression of diabetes.
Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 2010; 87(1): 4–14.
Guariguata L, Whiting DR, Hambleton I, Beagley J, Linnenkamp U, Shaw JE. Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract 2014; 103(2): 137–149.
King AJ. The use of animal models in diabetes research. Br J Pharmacol 2012; 166(3): 877–894.
Cohran VC, Bates MD. Leptin signaling and obesity: weight and see. Gastroenterology 2003; 124(5): 1546–1548.
Lewis GF, Carpentier A, Adeli K, Giacca A. Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes. Endocr Rev 2002; 23(2): 201–229.
Hummel KP, Dickie MM, Coleman DL. Diabetes, a new mutation in the mouse. Science 1966; 153(3740): 1127–1128.
Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E, Flier JS. Role of leptin in the neuroendocrine response to fasting. Nature 1996; 382(6588): 250–252.
Chen H, Charlat O, Tartaglia LA, Woolf EA, Weng X, Ellis SJ, Lakey ND, Culpepper J, Moore KJ, Breitbart RE, Duyk GM, Tepper RI, Morgenstern JP. Evidence that the diabetes gene encodes the leptin receptor: identification of a mutation in the leptin receptor gene in db/db mice. Cell 1996; 84(3): 491–495.
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372(6505): 425–432.
Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, Collins F. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 1995; 269(5223): 540–543.
Heiman ML, Ahima RS, Craft LS, Schoner B, Stephens TW, Flier JS. Leptin inhibition of the hypothalamic-pituitary-adrenal axis in response to stress. Endocrinology 1997; 138(9): 3859–3863.
Brandi LS, Bertolini R, Calafa M. Indirect calorimetry in critically ill patients: clinical applications and practical advice. Nutrition 1997; 13(4): 349–358.
Battezzati A, Viganò R. Indirect calorimetry and nutritional problems in clinical practice. Acta Diabetol 2001; 38(1): 1–5.
Schwenk A, Meriläinen PT, Macallan DC. Indirect calorimetry in patients with active respiratory infection—prevention of cross-infection. Clin Nutr 2002; 21(5): 385–388.
G LK. Measurements in physical therapy by Jules M. Rothstein Clinics in Physical Therapy Vol. 7. Churchill Livingstone, 1985. £27.50. Clin Biomech (Bristol, Avon) 1987; 2(1): 61.
Osborn O, Sanchez-Alavez M, Brownell SE, Ross B, Klaus J, Dubins J, Beutler B, Conti B, Bartfai T. Metabolic characterization of a mouse deficient in all known leptin receptor isoforms. Cell Mol Neurobiol 2010; 30(1): 23–33.
Li YY, Yu LF, Zhang LN, Qiu BY, Su MB, Wu F, Chen DK, Pang T, Gu M, Zhang W, Ma WP, Jiang HW, Li JY, Nan FJ, Li J. Novel small-molecule AMPK activator orally exerts beneficial effects on diabetic db/db mice. Toxicol Appl Pharmacol 2013; 273(2): 325–334.
Muoio DM, Lynis Dohm G. Peripheral metabolic actions of leptin. Best Pract Res Clin Endocrinol Metab 2002; 16(4): 653–666.
Harris RB, Mitchell TD, Yan X, Simpson JS, Redmann SM Jr. Metabolic responses to leptin in obese db/db mice are strain dependent. Am J Physiol Regul Integr Comp Physiol 2001; 281(1): R115–132.
Trayhurn P, James W P. Thermoregulation and non-shivering thermogenesis in the genetically obese (ob/ob) mouse. Pflugers Arch 1978; 373(2): 189–193.
Lee SM, Bressler R. Prevention of diabetic nephropathy by diet control in the db/db mouse. Diabetes 1981; 30(2): 106–111.
Edgel KA, McMillen TS, Wei H, Pamir N, Houston BA, Caldwell MT, Mai PO, Oram JF, Tang C, Leboeuf RC. Obesity and weight loss result in increased adipose tissue ABCG1 expression in db/db mice. Biochim Biophys Acta 2012; 1821(3): 425–434.
Dittrich HM, Hahn von Dorsche H. [The anatomical and histological investigation of the pancreas in the 19th century and till the discovery of insulin (1921). 2. The pancreas research from the discovery of islets (1869) till the discovery of pancreas-diabetes (1889) (author’s transl)]. Anat Anz 1978; 143(3): 231–241.
About this article
Cite this article
Choi, HM., Kim, H.R., Kim, EK. et al. An age-dependent alteration of the respiratory exchange ratio in the db/db mouse. Lab Anim Res 31, 1–6 (2015). https://doi.org/10.5625/lar.2015.31.1.1