Adipose browning response to burn trauma is impaired with aging

Abdullahi, Abdikarim; Knuth, Carly M.; Auger, Christopher; Sivayoganathan, Thibacg; Parousis, Alexandra; Jeschke, Marc G.

doi:10.1172/jci.insight.143451

Cited by 9 publications

(9 citation statements)

References 40 publications

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“…Additionally, it was found that chemotaxis index increased with age ( 36 ), and that chemotaxis towards CCL2 was more robust in old bone marrow-derived macrophages (BMDMs) from C57BL/6 mice, enhanced further by sFASL ( 37 ). In contrast, chemotaxis was found to decrease with age in the final two publications, one assessing white adipose tissue in burns ( 38 ), the other looking at exercise, with aged controls having significantly less capacity for chemotaxis than young ( 39 ).…”

Section: Resultsmentioning

confidence: 99%

“…It has not yet been characterised in ageing more extensively than reduced cytokine secretion after PAMP recognition (41). Overall chemotaxis was found to be increased in two publications (36,37) and decreased in three with age (35,38,39), although changes with age were found in each instance supporting the notion of immune system dysfunction with age. There is a clear need for more research into macrophage functional decline with age and the mechanisms behind this.…”

Section: Discussionmentioning

confidence: 96%

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Markers of the ageing macrophage: a systematic review and meta-analysis

Moss,

Phipps,

Wilson

et al. 2023

Front. Immunol.

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IntroductionAgeing research is establishing macrophages as key immune system regulators that undergo functional decline. Due to heterogeneity between species and tissue populations, a plethora of data exist and the power of scientific conclusions can vary substantially. This meta-analysis by information content (MAIC) and systematic literature review (SLR) aims to determine overall changes in macrophage gene and protein expression, as well as function, with age. MethodsPubMed was utilized to collate peer-reviewed literature relating to macrophage ageing. Primary studies comparing macrophages in at least two age groups were included. Data pertaining to gene or protein expression alongside method used were extracted for MAIC analysis. For SLR analysis, data included all macrophage-specific changes with age, as well as species, ontogeny and age of groups assessed. ResultsA total of 240 studies were included; 122 of which qualified for MAIC. The majority of papers focussed on changes in macrophage count/infiltration as a function of age, followed by gene and protein expression. The MAIC found iNOS and TNF to be the most commonly investigated entities, with 328 genes and 175 proteins showing consistent dysregulation with age across the literature. Overall findings indicate that cytokine secretion and phagocytosis are reduced and reactive oxygen species production is increased in the ageing macrophage.DiscussionCollectively, our analysis identifies critical regulators in macrophage ageing that are consistently dysregulated, highlighting a plethora of targets for further investigation. Consistent functional changes with age found here can be used to confirm an ageing macrophage phenotype in specific studies and experimental models.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 96%

Markers of the ageing macrophage: a systematic review and meta-analysis

Moss,

Phipps,

Wilson

et al. 2023

Front. Immunol.

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“…Our prior studies, both in burn patients and murine models, have demonstrated heightened activation and expression of signaling components related to ER stress (p-ERK1/2, cleaved-ATF6), lipolysis (p-HSL, ATGL, FGF21), and browning (UCP1), which are key hallmarks of the pathophysiological response to burn injury (27,28). However, there is currently a lack of knowledge regarding the S-acylation status of these proteins.…”

Section: Discussionmentioning

confidence: 99%

Burns Induce Alterations in the Acyl Proteome of Mice and Humans

Bieerkehazhi,

Barayan,

Khalaf

et al. 2024

Shock

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Hypermetabolic reprogramming triggered by thermal injury causes substantial morbidity and mortality. Despite the therapeutic potential of targeting this response, the underlying mechanisms remain poorly understood. Interestingly, protein S-acylation is a reversible post-translational modification induced by metabolic alterations via DHHC acyltransferases. While this modification aids in the regulation of cellular functions, deregulated S-acylation contributes to various diseases by altering protein structure, stability, and localization. However, whether and how S-acylation may impact morbidity and mortality during post-burn hypermetabolism is unknown. In this study, we discovered that alterations in the acyl proteome play a key role in mediating adverse outcomes that occur after burn injury. Using a murine model, we show that burn injury induces profound changes in the expression of various DHHC isoforms in metabolic organs central to regulating post-burn hypermetabolism, the adipose tissue and liver. This was accompanied by increased levels of S-acylated proteins in several pathways involved in mediating the adverse hypermetabolic response, including ER stress, lipolysis, and browning. In fact, similar results were also observed in adipose tissue from severely burned patients, as reflected by increased S-acylation of ERK1/2, eIF2a, ATGL, FGF21, and UCP1 relative to non-burn controls. Importantly, pharmacologically targeting this post-translational modification using a non-selective DHHC inhibitor effectively attenuated burn-induced ER stress, lipolysis, and browning induction in an ex vivo explant model. Together, these findings suggest that S-acylation may facilitate the protein activation profile that drives burn-induced hypermetabolism and that targeting it could potentially be an effective strategy to restore metabolic function and improve outcomes after injury.

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“…For example, it has been suggested that the increased rates of morbidity and mortality in elderly patients may be due to a failure to induce a hypermetabolic state, which was associated with the lack of adipose tissue browning. 39 …”

Section: Discussionmentioning

confidence: 99%

Adipose browning response to burn trauma is impaired with aging

Cited by 9 publications

References 40 publications

Markers of the ageing macrophage: a systematic review and meta-analysis

Markers of the ageing macrophage: a systematic review and meta-analysis

Burns Induce Alterations in the Acyl Proteome of Mice and Humans

Subcutaneous white adipose tissue independently regulates burn-induced hypermetabolism via immune-adipose crosstalk

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