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Dong-Hwan Kim1, **
, Jeong Min Cho2, **, Min Joon Seo3, 4, Ju Hyun Lim4, Hae-Rahn Bae1, 4
, Jeong Min Cho2, **, Min Joon Seo3, 4, Ju Hyun Lim4, Hae-Rahn Bae1, 4
Abstract
Purpose
Obesity is associated with a dysregulation of metabolic balance and is regarded as a low grade chronic inflammation. Western-style diet and physical inactivity are leading causes of obesity. This study examined the profiles of forty plasma cytokines and chemokines at the same time in the early stages of high-fat diet-induced obesity using a mouse model.
Methods
A total of 30 male CD1 mice, 12 ~ 14 weeks of age, were enrolled. The mice were fed a high-fat diet for 6 weeks to induce obesity. The plasma glucose and triglyceride concentrations were measured using a hexokinase colorimetric assay kit and a serum triglyceride determination kit, respectively. The relative levels of multiple cytokines and chemokines in the plasma were determined using a mouse cytokine array kit.
Results
The mice exhibited significant weight gain after 6 weeks of a high-fat diet. The genital fat depot was enlarged along with an increase in the number and the mean size of white adipocytes as early as 4 weeks after a high-fat diet. In addition, the plasma glucose and triglyceride levels increased significantly after 4 weeks of a high-fat diet. Cytokine array analysis revealed a remarkable increase in the expression of both CXCL12 and CXCL13, whereas the proinflammatory cytokines remained low after 4 weeks of a high-fat diet.
Conclusion
A significant increase in plasma levels of CXCL12 and CXCL13 was observed after 4 weeks of a high-fat diet, which might induce the migration of B lymphocytes, T lymphocytes, and monocytes from the blood to expanding adipose tissue or fat associated lymphoid clusters, playing a key role in adipose tissue remodeling and local immunity during the early stages of high-fat diet-induced obesity.
Figures and Tables
Fig. 1
Changes in body weights and food intake after a high-fat diet. The body weights (A) and the amount of food intake (B) of CD1 mice were measured for 6 weeks of normal (Control) or a high-fat diet (HFD). Note the significant weight gain after 6 weeks of a high-fat diet with no change in food intake (mean ± SE, * p < 0.05).
Fig. 2
Changes in organ weights after a high-fat diet. Heart (A), liver (B) and hamstring muscle (C) of CD1 mice were extracted after 4 weeks (HF-4W) and 6 weeks (HF-6W) of normal (CON) or a high-fat diet and weighed. Note that the weight of liver increased while that of hamstring muscle decreased after 6 week high-fat diet (mean ± SE, * p < 0.05).
Fig. 3
Changes in adipose tissue mass after a high-fat diet. Genital (A), inguinal (B) and interscapular adipose tissues (C) of CD1 mice were extracted after 4 weeks (HF-4W) and 6 weeks (HF-6W) of normal (CON) or a high-fat diet and weighed. Note that weights of genital fat depots increased while those of interscapular fat depots decreased after 6 week high-fat diet (mean ± SE, * p < 0.05).
Fig. 4
Histological analysis of adipose tissues after a high-fat diet. Genital, inguinal and interscapular adipose tissues of CD1 mice were paraffin sectioned and stained with hematoxylin and eosin after 4 weeks (HF-4W) and 6 weeks (HF-6W) of normal (CON) or a high-fat diet. Note that the number and the mean size of white adipocytes increased as early as 4 weeks following a high-fat diet.
Fig. 5
Changes in plasma glucose and triglyceride levels after a high-fat diet. Concentrations of plasma glucose (A) and triglyceride (B) were measured after 4 weeks (HF-4W) and 6 weeks (HF-6W) of a high-fat diet or normal diet (CON). Note that the plasma glucose and triglyceride levels significantly increased after 4 weeks of a high-fat diet (mean ± SE, * p < 0.05, ** p < 0.01).
Fig. 6
Representative blots of mouse plasma cytokine array after a high-fat diet. Plasma cytokine and chemokine profiles were assessed using a mouse cytokine array kit after 4 weeks of normal (CON) or a high-fat diet (HF-4W). The dots exhibiting stronger density in HF-4W than CON are boxed in red, whereas those exhibiting weaker density in HF-4W than CON are boxed in blue. The dots with gray boxes correspond to those showing similar densities between the two groups. Note that CXCL12 and CXCL13 spots remarkably increased after 4 weeks of a high-fat diet. Representative blots from 3 individual experiments.
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