Browning of white adipose tissue after a burn injury promotes hepatic steatosis and dysfunction
- PMID: 31740668
- PMCID: PMC6861318
- DOI: 10.1038/s41419-019-2103-2
Browning of white adipose tissue after a burn injury promotes hepatic steatosis and dysfunction
Abstract
Burn patients experiencing hypermetabolism develop hepatic steatosis, which is associated with liver failure and poor outcomes after the injury. These same patients also undergo white adipose tissue (WAT) browning, which has been implicated in mediating post-burn cachexia and sustained hypermetabolism. Despite the clinical presentation of hepatic steatosis and WAT browning in burns, whether or not these two pathological responses are linked remains poorly understood. Here, we show that the burn-induced WAT browning and its associated increased lipolysis leads to the accelerated development of hepatic steatosis in mice. Deletion of interleukin 6 (IL-6) and the uncoupling protein 1 (UCP1), regulators of burn-induced WAT browning completely protected mice from hepatic steatosis after the injury. Treatment of post-burn mice with propranolol or IL-6 receptor blocker attenuated burn-induced WAT browning and its associated hepatic steatosis pathology. Lipidomic profiling in the plasma of post-burn mice and burn patients revealed elevated levels of damage-inducing lipids (palmitic and stearic acids), which induced hepatic endoplasmic reticulum (ER) stress and compromised hepatic fat oxidation. Mechanistically, we show that hepatic ER stress after a burn injury leads to a greater ER-mitochondria interaction, hepatocyte apoptosis, oxidative stress, and impaired fat oxidation. Collectively, our findings uncover an adverse "cross-talk" between the adipose and liver tissue in the context of burn injury, which is critically mediated by WAT browning.
Conflict of interest statement
The authors declare that they have no conflict of interest.
Figures
![Fig. 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6861318/bin/41419_2019_2103_Fig1_HTML.gif)
![Fig. 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6861318/bin/41419_2019_2103_Fig2_HTML.gif)
![Fig. 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6861318/bin/41419_2019_2103_Fig3_HTML.gif)
![Fig. 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6861318/bin/41419_2019_2103_Fig4_HTML.gif)
![Fig. 5](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6861318/bin/41419_2019_2103_Fig5_HTML.gif)
![Fig. 6](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6861318/bin/41419_2019_2103_Fig6_HTML.gif)
![Fig. 7](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6861318/bin/41419_2019_2103_Fig7_HTML.gif)
Similar articles
-
Lactate shuttling drives the browning of white adipose tissue after burn.Am J Physiol Endocrinol Metab. 2023 Sep 1;325(3):E180-E191. doi: 10.1152/ajpendo.00084.2023. Epub 2023 Jul 5. Am J Physiol Endocrinol Metab. 2023. PMID: 37406182
-
Taming the Flames: Targeting White Adipose Tissue Browning in Hypermetabolic Conditions.Endocr Rev. 2017 Dec 1;38(6):538-549. doi: 10.1210/er.2017-00163. Endocr Rev. 2017. PMID: 28938469 Free PMC article. Review.
-
Alternatively Activated Macrophages Drive Browning of White Adipose Tissue in Burns.Ann Surg. 2019 Mar;269(3):554-563. doi: 10.1097/SLA.0000000000002465. Ann Surg. 2019. PMID: 28817438 Free PMC article.
-
IL-6 Signal From the Bone Marrow is Required for the Browning of White Adipose Tissue Post Burn Injury.Shock. 2017 Jan;47(1):33-39. doi: 10.1097/SHK.0000000000000749. Shock. 2017. PMID: 27648696 Free PMC article.
-
White Adipose Tissue Browning: A Double-edged Sword.Trends Endocrinol Metab. 2016 Aug;27(8):542-552. doi: 10.1016/j.tem.2016.06.006. Epub 2016 Jul 5. Trends Endocrinol Metab. 2016. PMID: 27397607 Free PMC article. Review.
Cited by
-
The Different Shades of Thermogenic Adipose Tissue.Curr Obes Rep. 2024 Apr 12. doi: 10.1007/s13679-024-00559-y. Online ahead of print. Curr Obes Rep. 2024. PMID: 38607478 Review.
-
Subcutaneous white adipose tissue independently regulates burn-induced hypermetabolism via immune-adipose crosstalk.Cell Rep. 2024 Jan 23;43(1):113584. doi: 10.1016/j.celrep.2023.113584. Epub 2023 Dec 20. Cell Rep. 2024. PMID: 38117653 Free PMC article.
-
Lactate shuttling drives the browning of white adipose tissue after burn.Am J Physiol Endocrinol Metab. 2023 Sep 1;325(3):E180-E191. doi: 10.1152/ajpendo.00084.2023. Epub 2023 Jul 5. Am J Physiol Endocrinol Metab. 2023. PMID: 37406182
-
Burn-Induced Apoptosis in the Livers of Aged Mice Is Associated With Caspase Cleavage of Bcl-xL.J Surg Res. 2023 Oct;290:147-155. doi: 10.1016/j.jss.2023.04.020. Epub 2023 May 31. J Surg Res. 2023. PMID: 37267704
-
Single-nuclei RNA Profiling Reveals Disruption of Adipokine and Inflammatory Signaling in Adipose Tissue of Burn Patients.Ann Surg. 2023 Dec 1;278(6):e1267-e1276. doi: 10.1097/SLA.0000000000005880. Epub 2023 Apr 14. Ann Surg. 2023. PMID: 37057618
References
Publication types
MeSH terms
Grants and funding
LinkOut - more resources
Full Text Sources
Medical
Research Materials