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. 2011 May;300(5):R1115-25.
doi: 10.1152/ajpregu.00806.2010. Epub 2011 Mar 2.

Exercise ameliorates high-fat diet-induced metabolic and vascular dysfunction, and increases adipocyte progenitor cell population in brown adipose tissue

Xiaohua Xu  1 , Zhekang Ying, Ming Cai, Zhaobin Xu, Yuanjing Li, Silis Y Jiang, Kevin Tzan, Aixia Wang, Sampath Parthasarathy, Guanglong He, Sanjay Rajagopalan, Qinghua Sun
Affiliations

Exercise ameliorates high-fat diet-induced metabolic and vascular dysfunction, and increases adipocyte progenitor cell population in brown adipose tissue

Xiaohua Xu et al. Am J Physiol Regul Integr Comp Physiol. 2011 May.

Abstract

A high-fat diet (HFD) is associated with adipose inflammation, which contributes to key components of metabolic syndrome, including obesity and insulin resistance. The increased visceral adipose tissue mass associated with obesity is the result of hyperplasia and hypertrophy of adipocytes. To investigate the effects of exercise on HFD-induced metabolic disorders, male C57BL/6 mice were divided into four groups: SED (sedentary)-ND (normal diet), EX (exercise)-ND, SED-HFD, and EX-HFD. Exercise was performed on a motorized treadmill at 15 m/min, 40 min/day, and 5 day/wk for 8 wk. Exercise resulted in a decrease in abdominal fat contents and inflammation, improvements in glucose tolerance and insulin resistance, and enhancement of vascular constriction and relaxation responses. Exercise with or without HFD increased putative brown adipocyte progenitor cells in brown adipose tissue compared with groups with the same diet, with an increase in brown adipocyte-specific gene expression in brown and white adipose tissue. Exercise training enhanced in vitro differentiation of the preadipocytes from brown adipose depots into brown adipocytes and enhanced the expression of uncoupling protein 1. These findings suggest that exercise ameliorates high-fat diet-induced metabolic disorders and vascular dysfunction, and increases adipose progenitor cell population in brown adipose tissue, which might thereby contribute to enhanced functional brown adipose.

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Figures

Fig. 1.
Fig. 1.
Body weight gain after 8 wk of EX or diet intervention. *P < 0.05 vs. SED-ND at each time; **P < 0.001 vs. SED-ND; #P < 0.05 vs. EX-ND; ##P < 0.001 vs. EX-ND at each time; $P < 0.05 vs. SED-HFD at each time; n = 8. Pre, preintervention; SED, sedentary; EX, exercise; ND, standard normal diet; HFD, high-fat diet.
Fig. 2.
Fig. 2.
Blood glucose concentrations and homeostasis model assessment method-insulin resistance (HOMA-IR) index. Intraperitoneal glucose tolerance test (IPGTT) before (A) and after (B) exercise and/or diet intervention. C: glucose area under the curve calculated from the glucose tolerance test from B. D: HOMA-IR index. *P < 0.05 vs. SED-ND at each time; **P < 0.01 vs. SED-ND; #P < 0.05 vs. EX-ND, ##P < 0.01 vs. EX-ND at each time; $P < 0.05 vs. SED-HFD at each time; n = 8.
Fig. 3.
Fig. 3.
Measurement of abdominal fat mass and distribution by magnetic resonance imaging (MRI). Representative T1-weighted spin echo images of abdominal adipose tissues by MRI (A) and analytic data for percentage of total fat content in total abdominal mass (B), percentage of visceral fat (C), and subcutaneous fat (D) in total abdominal mass. E: macrophages (F4/80+ cells) expression via immunohistochemical staining in visceral adipose tissue. *P < 0.05 vs. SED-ND; **P < 0.001 vs. SED-ND; †P < 0.05 vs. SED-HFD; ‡P < 0.001 vs. SED-HFD; n = 8.
Fig. 4.
Fig. 4.
Vasomotor tone changes in aortic rings via myograph in response to phenylephrine (PE), acetylcholine (ACh), or sodium nitroprusside (SNP). A–D: vasomotor tone changes in response to PE (A), PE with NG-nitro-l- arginine methyl ester (l-NAME) (B), ACh (C), or SNP (D); n = 8. *P < 0.05 vs. SED-ND; #P < 0.05 vs. EX-ND, †P < 0.05 vs. SED-HFD. M, mol/l.
Fig. 5.
Fig. 5.
Representative transmission electronic microscopy image (A) and corresponding quantification of mitochondrial number (B) and size (C) in white adipose tissue (WAT) per field. Arrows indicate mitochondria (M). *P < 0.05 vs. SED-ND; #P < 0.05 vs. EX-ND; †P < 0.05 vs. SED-HFD; n = 8. Magnification, ×18,500.
Fig. 6.
Fig. 6.
A: schematic representation of the fluorescence-activated cell sorting (FACS) strategy. B: Dot plots showing FACS staining profiles and gating (black boxes) of adipose stromal vascular fraction. The live singlets were analyzed on the basis of lack of CD31 and Ter119 expression and were further separated on the basis of expression of CD45. CD45− cells (Lin−) were then analyzed on the basis of expression of CD34 and CD29, and the CD34+ cells were analyzed on the basis of staining for Sca-1 and CD24. C: representative dot plots for adipocyte progenitor cells (APC) by flow cytometry. D: analytic data for brown APC (Lin−:CD29+:CD34+:Sca-1+:CD24+). *P < 0.05 vs. SED-ND; †P < 0.05 vs. SED-HFD; n = 8.
Fig. 7.
Fig. 7.
Preadipocytes from brown adipose tissue were cultured and differentiated into adipocytes, which were examined by immunocytochemistry for uncoupling protein 1 (UCP1). Representative images (A and B) and statistical analysis (C) for immunohistochemistry of UCP1 in cells by in vitro study. Representative images (E and F) and statistical analysis (G) for immunohistochemistry of UCP1 in interscapular brown adipose tissue from mice fed HFD. *P < 0.05 vs. SED-HFD; **P < 0.001 vs. SED-HFD; n = 8. BAT, interscapular brown adipose tissue.
Fig. 8.
Fig. 8.
Brown adipocyte-specific gene expression in white adipose tissue. *P < 0.05 vs. SED-ND; **P < 0.001 vs. SED-ND; #P < 0.05 vs. EX-ND; †P < 0.05 vs. SED-HFD; n = 8. UCP1, uncoupling protein 1; PRDM16, PRD1-BF1-RIZ1, homologous domain containing 16; C/EBPβ, CCAAT enhancing binding protein β; Pparg2, peroxisome proliferator-activated receptor-γ 2; PGC-1α, peroxisome proliferator-activated receptor-γ coactivator 1-α; Dio2, type 2 iodothyronine deiondinase.
Fig. 9.
Fig. 9.
Brown adipocyte-specific gene expression in brown adipose tissue. *P < 0.05 vs. SED-ND; **P < 0.001 vs. SED-ND; n = 8. PRDM16, PRD1-BF1-RIZ1 homologous domain containing 16.
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