Calorie Restriction Combined with High-Intensity Interval Training Promotes Browning of White Adipose Tissue by Activating the PPARγ/PGC-1α/UCP1 Pathway.

Objective: This study was designed to survey the effect and the mechanism of action of calorie restriction combined with high-intensity interval training (HIIT) on the browning of white adipose tissue. Methods: For the human study population, obese adult males were randomly assigned to one of three major groups: the control group (CN group), the calorie restriction combined with HIIT group (CR+HIIT group) and the HIIT group. After 3 months of training, body composition was measured. For the rodent study population, Sprague Dawley rats were randomly split into a normal diet control group (CON group) and an obesity model group. After successful obesity modeling, the latter was divided into the obesity control group (HON group), the calorie restriction plus HIIT group (ONE group) and the HIIT group (OHE group), with 8 animals in each group. A treadmill was used for training 5 days a week for 10 weeks. The messenger RNA (mRNA) expression of uncoupling protein 1 (UCP1), Prdm16 gene, and Cidea gene in visceral adipose tissue were detected with real-time polymer chain reaction (RT-qPCR), while the protein levels of UCP1, PPARγ and PGC-1α in visceral adipose tissue (VAT) were detected by western blot analysis. Results: Body weight and body fat rate in the human experiments demonstrated that fat mass, body weight and body fat rate in the CR+HIIT group were clearly lower than in the CN group. In the rat model, the body fat rate and body weight in the HON group were significantly higher than in the CON group, which indicated that the obesity model was successfully generated. As expected, the body fat rate and body weight in the ONE and OHE groups were considerably lower than in the HON group. Moreover, the body fat rate in the ONE group was considerably lower than in the OHE group. Further investigation indicated that the area under this curve (AUC) of oral glucose tolerance test (AUCOGTT), insulin (INS) levels and fasting blood glucose (FBG) levels in the HON group were more significantly increased than in the CON group, while AUCOGTT and INS levels in the ONE and OHE groups were considerably lower than in the HON group. Hematoxylin and eosin (H&E) staining showed that, compared with the CON group, the adipocyte area in the HON group was expanded, but narrowed in the ONE and OHE groups. In addition, the adipocyte area in the ONE group was apparently smaller than in the OHE group. We also compared molecular markers among the groups. RT-qPCR analysis showed that the expression of UCP1, Prdm16 and Cidea had been downregulated in the HON group compared with CON group but upregulated in the HON group compared with the ONE and OHE groups. Western blot analysis indicated that UCP1 in the HON group was lower than in the CON group but higher than in the ONE and OHE groups. In addition, the protein level of UCP1 was upregulated in the ONE group compared with the OHE group. Furthermore, expression levels of PPARγ coactivator-1α (PGC-1α) and peroxisome proliferator-activated receptor gamma (PPARγ) were downregulated in the HON group compared with the CON group, then further downregulated in the ONE and OHE groups compared with the HON group. In addition, the PGC-1α level in the ONE group was greatly improved compared with the OHE group. Conclusion: Calorie restriction integrated with HIIT and HIIT alone upregulates PPARγ, PGC- 1α, as well as UCP1 in VAT of obese rats, promoting the browning of visceral fat and ultimately achieving fat loss. Calorie restriction integrated with HIIT is more effective than HIIT alone for fat loss.