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Abstract
Background
Food restriction has been reported to ameliorate diabetes and obesity. In this study, we examined the effects of the food restriction on phenotypes of TALLYHO/JngJ (TH) mouse, a recently developed diabetic model animal.
Methods
3 week-old TH mice were divided into 2 groups (n = 20 each for food-restricted (THR) and free-fed (THF)) and THR mice were fed the same amount of food as normal control mice (C57BL/6, n = 20). Body weight was weekly monitored till 14 weeks of age. The half of animals were sacrificed at 8 weeks of age, and liver, kidney, and fat weight were measured. The histopathology of liver and brown fat tissues and mRNA expression of leptin in adipose tissue were analyzed. The oral glucose tolerance test and insulin resistance test was done at 14 weeks of age. The plasma concentrations of glucose, free fatty acid, triglyceride, cholesterol and leptin were analyzed.
Results
The THR mice had lower body weights than the THF mice, similar to C57BL/6 mice, with reduced fat deposition in liver and brown fat tissue. The plasma levels of glucose, triglyceride and free fatty acid were decreased in the THR group. The THR mice, however, carried more fat than normal mice, with increased plasma leptin concentration and leptin mRNA expression in fats and no alteration in plasma cholesterol levels. Furthermore, the THR mice revealed glucose intolerance with impaired after-meal insulin secretion and slight insulin resistance.
Conclusion
The food restriction apparently ameliorated the obesity and diabetic phenotypes of TH mice. However, plasma concentration of cholesterol were not improved in THR mice with increased adiposity index and glucose intolerance, suggesting the genetically prone tendency of obesity and diabetes development in TH mice possibly with an impairment in cholesterol metabolism.
Figures and Tables
Fig. 1
Effect of food restriction on body weight in TH mice. A. Body weight changes of free-fed TH (THF), food-restricted TH (THR) and C57BL/6 mice from 3 to 14 weeks of age (n = 10 each). B. Average food intake rate. *indicate P < 0.01, vs THF and †P < 0.01, vs C57BL/6, respectively.
Fig. 2
Effect of food restriction on fat doposition in liver and brown adipose tissues. Microscopic appearance of liver with H-E (left panel) and Oil red O staining (middle panel) and of brown fat with HE staining (right panel) at 8 weeks of age. A, D, and G: C57BL/6. B, E and H: free-fed TH (THF). C, F and I: food-restricted TH mice (THR). BAT, Brown adipose tissue.
Fig. 3
Effect of food restriction on plasma leptin concentration and mRNA expression in adipose tissues at 8 weeks of age. A. Plasma leptin concentration (n = 10 each). B. mRNA expression of leptin in subcutanous fat tissue (n = 4 each). C. mRNA expression of leptin in reproductive fat tissue (n = 4 each). *, †, and ‡ indicate P < 0.05, P < 0.01, and P < 0.005, vs THF, respectively and §, ¶, and **, indicate P < 0.05, P < 0.01, and P < 0.005, vs C57BL/6, respectively. THF, free-fed TallyHo mice; THR, food-restricted TallyHo mice.
Fig. 4
Effect of food restriction on glucose intolerance and insulin secretion. A. Oral glucose tolerance test (OGTT) at 8 weeks of age (n = 10/group) (left) and. Area under the curve of glucose (right) at 8 weeks of age. B. OGTT at 14 weeks of age (n = 10/group) (left) and Area under the curve of glucose (right) at 14 weeks. C. Insulin secretion during the OGTT at 14 weeks of age (left) and Area under the curve of insulin (right). *, † and ‡ indicate P < 0.05, P < 0.01, and P < 0.005, vs THF and §P < 0.005 vs C57BL/6, respectively.
Fig. 5
Effects of food restriction on insulin tolerance. A. Changes in plasma glucose concentration during insulin tolerance test (ITT) at 14 weeks of age (n = 10/group). B. Area under the curve of glucose during ITT. * indicate P < 0.005 vs THF and † and ‡P < 0.05 and P < 0.005, vs C57BL/6, respectively.
Table. 1
Effect of food restriction on organ weight and ratio to body weight in mice at 8 weeks of age (n = 10/group)
Table. 2
Effect of food restriction on plasma biochemical parameters at 8 and 14 weeks of age (n = 10/group)
FFA, free fatty acid; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol; TG, triglyceride; Total-C, total choleseterol; THF, free-fed TallyHo mice; THR, food-restricted TallyHo mice. Data are expressed as the mean ± S.D, *P < 0.005, vs THF; †P < 0.005, vs C57BL/6. a is the value corrected with its body weight (/g).
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