PMID- 38540669 OWN - NLM STAT- MEDLINE DCOM- 20240329 LR - 20240330 IS - 2218-273X (Electronic) IS - 2218-273X (Linking) VI - 14 IP - 3 DP - 2024 Feb 20 TI - HIIT Promotes M2 Macrophage Polarization and Sympathetic Nerve Density to Induce Adipose Tissue Browning in T2DM Mice. LID - 10.3390/biom14030246 [doi] LID - 246 AB - Browning of white adipose tissue (WAT) is a focus of research in type 2 diabetes mellitus (T2DM) and metabolism, which may be a potential molecular mechanism for high-intensity interval training (HIIT) to improve T2DM. In this study, male C57BL/6J wild-type mice were subjected to an 8-week HIIT regimen following T2DM induction through a high-fat diet (HFD) combined with streptozotocin (STZ) injection. We found that HIIT improved glucose metabolism, body weight, and fat mass in T2DM mice. HIIT also decreased adipocyte size and induced browning of WAT. Our data revealed a decrease in TNFalpha and an increase in IL-10 with HIIT, although the expression of chemokines MCP-1 and CXCL14 was increased. We observed increased pan-macrophage infiltration induced by HIIT, along with a simultaneous decrease in the expression of M1 macrophage markers (iNOS and CD11c) and an increase in M2 macrophage markers (Arg1 and CD206), suggesting that HIIT promotes M2 macrophage polarization. Additionally, HIIT upregulated the expression of Slit3 and neurotrophic factors (BDNF and NGF). The expression of the sympathetic marker tyrosine hydroxylase (TH) and the nerve growth marker GAP43 was also increased, demonstrating the promotion of sympathetic nerve growth and density by HIIT. Notably, we observed macrophages co-localizing with TH, and HIIT induced the accumulation of M2 macrophages around sympathetic nerves, suggesting a potential association between M2 macrophages and increased density of sympathetic nerves. In conclusion, HIIT induces adipose tissue browning and improves glucose metabolism in T2DM mice by enhancing M2 macrophage polarization and promoting sympathetic nerve growth and density. FAU - Guo, Yifan AU - Guo Y AD - Shanghai Key Lab of Human Performance, Shanghai University of Sport, Shanghai 200438, China. AD - The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China. FAU - Zhang, Qilong AU - Zhang Q AD - Shanghai Key Lab of Human Performance, Shanghai University of Sport, Shanghai 200438, China. AD - The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China. FAU - Yang, Dan AU - Yang D AD - Shanghai Key Lab of Human Performance, Shanghai University of Sport, Shanghai 200438, China. AD - The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China. FAU - Chen, Peijie AU - Chen P AD - Shanghai Key Lab of Human Performance, Shanghai University of Sport, Shanghai 200438, China. AD - The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China. FAU - Xiao, Weihua AU - Xiao W AD - Shanghai Key Lab of Human Performance, Shanghai University of Sport, Shanghai 200438, China. AD - The Key Lab of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China. LA - eng GR - 32371185/the National Natural Science Foundation of China/ GR - 23010504200/the Shanghai Science and Technology Plan Project/ GR - 20SG50/Shanghai Education Development Foundation and Shanghai Municipale Education Commission/ GR - YJSCX-2023-018/the Research and Innovation Grant for Graduate Students, Shanghai University of Sport/ GR - 2022KF001/the Key Lab of Exercise and Health Sciences of Ministry of Education (Shanghai University of Sport)/ GR - 11DZ2261100/the Shanghai Key Lab of Human Performance (Shanghai University of Sport)/ PT - Journal Article DEP - 20240220 PL - Switzerland TA - Biomolecules JT - Biomolecules JID - 101596414 RN - IY9XDZ35W2 (Glucose) RN - 0 (Slit3 protein, mouse) RN - 0 (Membrane Proteins) SB - IM MH - Male MH - Animals MH - Mice MH - *Diabetes Mellitus, Type 2/metabolism MH - *High-Intensity Interval Training MH - Mice, Inbred C57BL MH - Adipose Tissue/metabolism MH - Macrophages/metabolism MH - Adipose Tissue, White/metabolism MH - Glucose/metabolism MH - Membrane Proteins/metabolism PMC - PMC10968334 OTO - NOTNLM OT - high-intensity interval training OT - innervation OT - macrophage OT - sympathetic nervous system OT - type 2 diabetes mellitus OT - white adipose tissue browning COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2024/03/28 06:45 MHDA- 2024/03/29 06:45 PMCR- 2024/02/20 CRDT- 2024/03/28 01:09 PHST- 2024/01/22 00:00 [received] PHST- 2024/02/12 00:00 [revised] PHST- 2024/02/18 00:00 [accepted] PHST- 2024/03/29 06:45 [medline] PHST- 2024/03/28 06:45 [pubmed] PHST- 2024/03/28 01:09 [entrez] PHST- 2024/02/20 00:00 [pmc-release] AID - biom14030246 [pii] AID - biomolecules-14-00246 [pii] AID - 10.3390/biom14030246 [doi] PST - epublish SO - Biomolecules. 2024 Feb 20;14(3):246. doi: 10.3390/biom14030246.