dc.contributor.author |
Feng, Tianshi |
|
dc.contributor.author |
Zhao, Xuemei |
|
dc.contributor.author |
Gu, Ping |
|
dc.contributor.author |
Yang, Wah |
|
dc.contributor.author |
Wang, Cunchuan |
|
dc.contributor.author |
Guo, Qingyu |
|
dc.contributor.author |
Long, Qiaoyun |
|
dc.contributor.author |
Liu, Qing |
|
dc.contributor.author |
Cheng, Ying |
|
dc.contributor.author |
Li, Jin |
|
dc.contributor.author |
Cheung, Cynthia Kwan Yui |
|
dc.contributor.author |
Wu, Donghai |
|
dc.contributor.author |
Kong, Xinyu |
|
dc.contributor.author |
Xu, Yong |
|
dc.contributor.author |
Ye, Dewei |
|
dc.contributor.author |
Hua, Shuang |
|
dc.contributor.author |
Loomes, Kerry |
|
dc.contributor.author |
Xu, Aimin |
|
dc.contributor.author |
Hui, Xiaoyan |
|
dc.coverage.spatial |
England |
|
dc.date.accessioned |
2022-10-18T02:56:21Z |
|
dc.date.available |
2022-10-18T02:56:21Z |
|
dc.date.issued |
2022-09-05 |
|
dc.identifier.citation |
(2022). Nature Communications, 13(1), 5208-. |
|
dc.identifier.issn |
2041-1723 |
|
dc.identifier.uri |
https://hdl.handle.net/2292/61615 |
|
dc.description.abstract |
Adipose tissue macrophage (ATM) inflammation is involved with meta-inflammation and pathology of metabolic complications. Here we report that in adipocytes, elevated lactate production, previously regarded as the waste product of glycolysis, serves as a danger signal to promote ATM polarization to an inflammatory state in the context of obesity. Adipocyte-selective deletion of lactate dehydrogenase A (Ldha), the enzyme converting pyruvate to lactate, protects mice from obesity-associated glucose intolerance and insulin resistance, accompanied by a lower percentage of inflammatory ATM and reduced production of pro-inflammatory cytokines such as interleukin 1β (IL-1β). Mechanistically, lactate, at its physiological concentration, fosters the activation of inflammatory macrophages by directly binding to the catalytic domain of prolyl hydroxylase domain-containing 2 (PHD2) in a competitive manner with α-ketoglutarate and stabilizes hypoxia inducible factor (HIF-1α). Lactate-induced IL-1β was abolished in PHD2-deficient macrophages. Human adipose lactate level is positively linked with local inflammatory features and insulin resistance index independent of the body mass index (BMI). Our study shows a critical function of adipocyte-derived lactate in promoting the pro-inflammatory microenvironment in adipose and identifies PHD2 as a direct sensor of lactate, which functions to connect chronic inflammation and energy metabolism. |
|
dc.format.medium |
Electronic |
|
dc.language |
eng |
|
dc.publisher |
Springer Nature |
|
dc.relation.ispartofseries |
Nature communications |
|
dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. |
|
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
|
dc.rights.uri |
https://creativecommons.org/licenses/by/4.0/ |
|
dc.subject |
Adipose Tissue |
|
dc.subject |
Adipocytes |
|
dc.subject |
Macrophages |
|
dc.subject |
Animals |
|
dc.subject |
Humans |
|
dc.subject |
Mice |
|
dc.subject |
Insulin Resistance |
|
dc.subject |
Obesity |
|
dc.subject |
Inflammation |
|
dc.subject |
Lactic Acid |
|
dc.subject |
Procollagen-Proline Dioxygenase |
|
dc.subject |
Prolyl Hydroxylases |
|
dc.subject |
Diabetes |
|
dc.subject |
Nutrition |
|
dc.subject |
2.1 Biological and endogenous factors |
|
dc.subject |
2 Aetiology |
|
dc.subject |
Inflammatory and immune system |
|
dc.subject |
Metabolic and endocrine |
|
dc.title |
Adipocyte-derived lactate is a signalling metabolite that potentiates adipose macrophage inflammation via targeting PHD2. |
|
dc.type |
Journal Article |
|
dc.identifier.doi |
10.1038/s41467-022-32871-3 |
|
pubs.issue |
1 |
|
pubs.begin-page |
5208 |
|
pubs.volume |
13 |
|
dc.date.updated |
2022-09-20T21:44:12Z |
|
dc.rights.holder |
Copyright: The authors |
en |
dc.identifier.pmid |
36064857 (pubmed) |
|
pubs.author-url |
https://www.ncbi.nlm.nih.gov/pubmed/36064857 |
|
pubs.publication-status |
Published |
|
dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
research-article |
|
pubs.subtype |
Journal Article |
|
pubs.elements-id |
919175 |
|
pubs.org-id |
Science |
|
pubs.org-id |
Biological Sciences |
|
pubs.org-id |
Science Research |
|
pubs.org-id |
Maurice Wilkins Centre (2010-2014) |
|
dc.identifier.eissn |
2041-1723 |
|
dc.identifier.pii |
10.1038/s41467-022-32871-3 |
|
pubs.number |
5208 |
|
pubs.record-created-at-source-date |
2022-09-21 |
|
pubs.online-publication-date |
2022-09-05 |
|