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Exp Clin Endocrinol Diabetes 2011; 119(4): 243-251
DOI: 10.1055/s-0030-1267202
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Obesity of TallyHO/JngJ Mouse Is Due to Increased Food Intake with Early Development of Leptin Resistance

S. D. Rhee1 , Y. Y. Sung1 , Y. S. Lee1 , J. Y. Kim1 , W. H. Jung1 , M. J. Kim1 , M.-S. Lee2 , M. K. Lee2 , S.-D. Yang1 , 3 , H. G. Cheon1 , 4
  • 1Center for Metabolic Syndrome Therapeutics, Korea Research Institute of Chemical Technology, Daejon, Korea
  • 2Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
  • 3Department of Biological Engineering, Yanbian University of Science and Technology, Yanji City, Jilin Province, China
  • 4Department of Pharmacology and Pharmaceutical Sciences, Gachon University of Medicine and Science, Incheon, Korea
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Publication History

received 04.05.2010 first decision 31.08.2010

accepted 20.09.2010

Publication Date:
28 October 2010 (online)

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Abstract

TALLYHO/JngJ (TallyHo) mouse is a recently established animal model for type 2 diabetes mellitus (T2DM) with phenotypes of mild obesity and male-limited hyperglycemia. In this study, we investigated how obesity develops in TallyHo mice by measuring parameters of food intake and energy expenditure. At 4 weeks of age, TallyHo mice were heavier than control C57BL/6 mice with increased food intake but comparable energy expenditure parameters, such as body temperature, cold-induced thermogenesis, oxygen consumption rate (VO2) and spontaneous locomotor activity. Furthermore, pair-fed TallyHo mice, which were fed the same amount of food as C57BL/6 mice, showed similar patterns of body weight gain to C57BL/6 mice at all ages, implying that obesity in TallyHo mice may develop by increased food intake but not by decreased energy consumption. TallyHo mice appear to have hypothalamic leptin resistance at 4 weeks of age, as indicated by the increased expression of orexigenic neuropeptides in the hypothalamus and no alteration of food intake and neuropeptide expression upon intravenous leptin treatment. Leptin injection to TallyHo mice, however, increased the phosphorylation of STAT3 and Akt, an important signaling mediator of leptin, in a pattern similar to that in C57BL/6 mice. In conclusion, increased food intake is a crucial component in the development of obesity in TallyHo mice, in which central leptin resistance, possibly caused by uncoupling between activation of leptin signaling and neuropeptide expression, might be involved.

Key words

tallyho mice - leptin - food intake - energy expenditure - obesity

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Correspondence

H. G. Cheon,PhD 

Department of Pharmacology and Pharmaceutical Sciences

Gachon University of Medicine and Science

Yeonsu-3 dong

Yeonsu-Gu

406-799 Incheon

Korea

Phone: +82/32/820 4761

Fax: +82/32/820 4744

Email: hgcheon@gachon.ac.kr

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