Lactate Is a Key Mediator That Links Obesity to Insulin Resistance via Modulating Cytokine Production From Adipose Tissue
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Abstract
Numerous evidence indicates that inflammation in adipose tissue is the primary cause of systemic insulin resistance induced by obesity. Obesity-associated changes in circulating LPS level and hypoxia/HIF-1α activation have been proposed to be involved in boosting obesity-induced inflammation. However, there is poor understanding of what triggers obesity-induced inflammation. In this study, we pinpoint lactate as a key trigger to mediate obesity-induced inflammation and systemic insulin resistance. Specific deletion of Slc16a1 that encodes MCT1, the primary lactate transporter in adipose tissues, robustly elevates blood levels of proinflammatory cytokines and aggravates systemic insulin resistance without alteration of adiposity in mice fed high-fat diet. Slc16a1 deletion in adipocytes elevates intracellular lactate level while reducing circulating lactate concentration. Mechanistically, lactate retention due to Slc16a1 deletion initiates adipocyte apoptosis and cytokine release. The locally recruited macrophages amplify the inflammation by release of proinflammatory cytokines to the circulation, leading to insulin resistance in peripheral tissues. This study, therefore, indicates that lactate within adipocytes has a key biological function linking obesity to insulin resistance, and harnessing lactate in adipocytes can be a promising strategy to break this link.
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HIT facilitates the browning of adipose tissue and inhibits fat synthesis via lactate.
“However, HIT has been demonstrated to facilitate the browning of adipose tissue [53] and inhibit fat synthesis via lactate [32].”
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 [53]
The section “MCT1 Mediates Lactate Efflux in Adipocytes and Affects Adipocyte Differentiation” reports that blocking MCT1 increased intracellular lactate and reduced lipid accumulation in cultured adipocytes. It does not study HIT or show that HIT inhibits fat synthesis via lactate. The browning clause is attached to a different citation [53]. (LLM, conf=0.78)
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Cheng, B., Du, J., Tian, S., Zhang, Z., Chen, W., & Liu, Y. (2024) · Lipids in Health and Disease · doi:10.1186/s12944-024-02397-2 · Cited by 12 · see citing works
- Authors
- Lin, Y., Bai, M., Wang, S., Chen, L., Li, Z., Li, C., Cao, P., & Chen, Y.
- Affiliations
- Shanghai Institute of Nutrition and Health (CN)
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China
- ShanghaiTech University (CN)
- Corresponding author
- Chen, Yan
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2022-01-19
- Volume
- 71
- Issue
- 4
- Pages
- 637-652
- ISSN
- 0012-1797 (ISSN-L)
- OpenAlex
- W4205258973
- Cited by
- 99
- References
- 44
- Citations by year
- 2026: 15 · 2025: 36 · 2024: 25 · 2023: 20 · 2022: 3
- FWCI
- 15.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (31630036)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- lactate, obesity, insulin resistance, adipose tissue inflammation, MCT1, lactate transporters, adipocyte apoptosis, macrophages, inflammatory cytokines, high-fat diet, adipocytes
- MeSH terms
- Adipose Tissue, Animals, Inflammation, Insulin Resistance, Obesity, Cytokines, Lactic Acid, Mice, Diet, High-Fat
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