HIIT Promotes M2 Macrophage Polarization and Sympathetic Nerve Density to Induce Adipose Tissue Browning in T2DM Mice

Guo, Yifan; Zhang, Qilong; Yang, Dan; Chen, Peijie; Xiao, Weihua

doi:10.3390/biom14030246

Cited by 19Adipose Tissue and MetabolismAdipokines, Inflammation, and Metabolic DiseasesCardiovascular Disease and Adiposity

HIIT Promotes M2 Macrophage Polarization and Sympathetic Nerve Density to Induce Adipose Tissue Browning in T2DM Mice

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Guo, Yifan, Zhang, Qilong, Yang, Dan, Chen, Peijie, Xiao, Weihua·2024·Biomolecules

DOI 10.3390/biom14030246PMC PMC10968334

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Abstract

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 TNFα 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.

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Enhanced sensitivity to lipolytic hormones, increased browning thermogenesis, and lactylation of fatty acid synthase are involved in the post-exercise fat loss process associated with HIT.
“Enhanced sensitivity to lipolytic hormones [26], increased browning thermogenesis [31] and lactylation of fatty acid synthase [32] have been demonstrated to be involved in the post-exercise fat loss process associated with HIT.”
From High-intensity interval training or lactate administration combined with aerobic training enhances visceral fat loss while promoting VMH neuroplasticity in female rats (2024) · cites this paper as [31]

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Authors: Guo, Y., Zhang, Q., Yang, D., Chen, P., & Xiao, W.
Affiliations: Shanghai University of Sport (CN)
Corresponding author: Chen, Peijie
Xiao, Weihua
ORCID: Guo, Yifan
Yang, Dan
Chen, Peijie
Xiao, Weihua
Venue: Biomolecules
Publisher: MDPI AG
Published: 2024-02-20
Volume: 14
Issue: 3
Pages: 246
ISSN: 2218-273X (ISSN-L)
DOI: 10.3390/biom14030246
PMC: PMC10968334
OpenAlex: W4391964163
Cited by: 19
References: 36
Citations by year: 2026: 7 · 2025: 7 · 2024: 5
FWCI: 5.41
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Biomolecules (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Natural Science Foundation of China (32371185, 23010504200, 20SG50, 2020125, YJSCX-2023-018, 2022KF001, 11DZ2261100)
Shanghai Science and Technology Plan Project (32371185, 23010504200, 20SG50, 2020125, YJSCX-2023-018, 2022KF001, 11DZ2261100)
Shanghai Education Development Foundation and Shanghai Municipal Education Commission (32371185, 23010504200, 20SG50, 2020125, YJSCX-2023-018, 2022KF001, 11DZ2261100)
Shanghai Talent Development Fund (32371185, 23010504200, 20SG50, 2020125, YJSCX-2023-018, 2022KF001, 11DZ2261100)
Research and Innovation Grant for Graduate Students, Shanghai University of Sport (32371185, 23010504200, 20SG50, 2020125, YJSCX-2023-018, 2022KF001, 11DZ2261100)
Key Lab of Exercise and Health Sciences of Ministry of Education (Shanghai University of Sport) (32371185, 23010504200, 20SG50, 2020125, YJSCX-2023-018, 2022KF001, 11DZ2261100)
Shanghai Key Lab of Human Performance (Shanghai University of Sport) (32371185, 23010504200, 20SG50, 2020125, YJSCX-2023-018, 2022KF001, 11DZ2261100)
Topics: Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
Keywords: high-intensity interval training, type 2 diabetes, white adipose tissue browning, M2 macrophage polarization, adipose tissue macrophages, glucose metabolism, TNF-α, IL-10, chemokines, SLIT3, brain-derived neurotrophic factor, nerve growth factor, tyrosine hydroxylase, GAP-43, high-fat diet, streptozotocin
MeSH terms: High-Intensity Interval Training, Adipose Tissue, Animals, Diabetes Mellitus, Type 2, Glucose, Macrophages, Male, Membrane Proteins, Mice, Inbred C57BL, Mice, Adipose Tissue, White

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HIIT Promotes M2 Macrophage Polarization and Sympathetic Nerve Density to Induce Adipose Tissue Browning in T2DM Mice

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