Objectives To establish a model of ApoE knockout mice with insulin resistance induced by high fat diet, and observed the effect of swimming training on serum free fatty acid (FFA) and the expression of peroxisome proliferator-activated receptor (PPAR-γ), carnitine palmitoy1 transferase-1 (CPT-I), medium-chain acy1-coenzyme A dehydrogenase (MCAD) mRNA, to explore the mechanisms that Why swimming training could improve insulin resistance.

Methods Twenty-six male ApoE knockout mice were randomly divided into groups: the high-fat diet group (HFD, n=13) and the high-fat diet group with exercise training (HFD+Ex, n=13). The HFD+Ex group were fed with high-fat diet with exercise training for 12 weeks. The treatment of HFD group was identical to the HFD+Ex group except to swimming training. And another ten healthy male C57BL/6J (ND, n=10) mice as the control group were, which were fed with normal diet for 12 weeks. After 12 weeks experiment, the mice were dissected, the livers were excided off immediately. Serum insulin, glucose were determined and Homa-IRI was calculated to ascertain the establishment of insulin resistance. Serum total cholesterol (TC), trigiyceride (TG), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), free fatty acid (FFA) were determined. The PPAR-γ, CPT-I, MCAD mRNA in liver were estimated by reverse transcription PCR (RT-PCR).

Results 1. Compared with the ND group, the body weight of the HFD group was significantly higher (p<0.05). Compared to the HFD group, the body weight of the HFD+Ex group was significantly lower (p<0.05). 2. Compared with the ND group, fasting glucose, insulin and Homa-IRI of the HFD group was significantly higher (p<0.01). Compared with the HFD group, fasting insulin, glucose and HOMA-IR of the HFD+Ex group was significantly lower (p<0.05, 0.01, 0.01). 3. Compared with the ND group, TC, LDL, FFA of HFD group was significantly higher (p<0.01), TC, LDL of the HFD+Ex group was still higher (p<0.01). Compared with the HFD group, TC, LDL, FFA of the HFD+Ex group was significantly lower (p<0.05, 0.05, 0.01), HDL was significantly higher (p<0.05). 4. Compared with the ND group, the expression of PPAR-γ, CPT-1, MCAD mRNA of the HFD group were significantly deceased (p<0.01); Compared with the HFD group, the expression of PPAR-γ, CPT-1, MCAD mRNA of the HFD group were significantly increased (p<0.01).

Conclusion 1. High-fat diet could induce insulin resistance of ApoE Knockout mice. 2. Swimming training could improve insulin resistance of ApoE knockout mice. 3. Swimming training could improve insulin resistance possibly through upregulating the expression of PPAR-γ, CPT-1, MCAD mRNA.