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The Role of White Adipose Tissue Remodeling in Mediating Burn-Induced Hypermetabolism.

Record Type:	Language materials, manuscript : Monograph/item
Title/Author:	The Role of White Adipose Tissue Remodeling in Mediating Burn-Induced Hypermetabolism./
Author:	Knuth, Carly Michelle.
Description:	1 online resource (176 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 85-05, Section: B.
Contained By:	Dissertations Abstracts International85-05B.
Subject:	Systematic biology. -
Online resource:	click for full text (PQDT)
ISBN:	9798380840316

The Role of White Adipose Tissue Remodeling in Mediating Burn-Induced Hypermetabolism.
Knuth, Carly Michelle.

The Role of White Adipose Tissue Remodeling in Mediating Burn-Induced Hypermetabolism. - 1 online resource (176 pages)

Source: Dissertations Abstracts International, Volume: 85-05, Section: B.

Thesis (Ph.D.)--University of Toronto (Canada), 2023.

Includes bibliographical references

Major burns represent one of the most severe forms of trauma due to the magnitude and persistence of an amalgamation of symptoms, including systemic inflammation, glucose and insulin signaling dysregulation and whole-body catabolism, together inducing a hypermetabolic response. Remarkably, hypermetabolism can persist for years after the initial injury, even after full wound closure. Given its pervasiveness, and based on strong correlations between hypermetabolic symptoms and the increased risk of sepsis, multi-organ failure, and death, discovering novel interventions geared towards mitigating hypermetabolism is a top priority to improve patient outcomes. One potential avenue is to target adipose tissue.It is now well-appreciated that adipose tissue is not simply a quiescent lipid storage vessel. Rather, it is profoundly adaptable and possess a wide array of functions that govern systemic metabolism. Moreover, adipose tissue has been implicated as the driving force mediating a diverse spectrum of metabolic pathologies. Thus, we hypothesized that adipose tissue is a central regulator of burn-induced hypermetabolism, and that by reducing its metabolic activity, this may alleviate poor outcomes.We first demonstrated, in both severe burn patients and mouse models of thermal injury, that white adipose tissue (WAT) remodeling, including increased lipolysis, mitochondrial biogenesis, and browning (i.e. the phenotypic switch of adipocytes towards an energy expending state), is initiated by multiple factors, such as adrenergic stimulation and systemic inflammation, and persists long-term. Moreover, this was associated with severe metabolic derangements, such as increased energy expenditure, inflammation and tissue-specific dysfunction. Given this correlative evidence, we next aimed to provide direct support that WAT drives hypermetabolism. Indeed, we showed that WAT can independently induce a systemic dysfunctional state when burn adipose is transplanted into healthy recipients. Remarkably, the dysfunctional phenotype was restored when healthy fat was transplanted into a burn model. This suggests that WAT can independently elicit or improve the hypermetabolic response. Finally, we uncovered a novel mechanism of intra-adipose remodeling, which coordinates an immune-adipocyte crosstalk facilitated by nicotinic acetylcholine receptor signaling. Collectively, this thesis clearly identifies WAT as a dominant mediator of the long-term hypermetabolic response to burns. Thus, future therapeutic interventions should be designed to target adipose metabolism.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2024

Mode of access: World Wide Web

ISBN: 9798380840316Subjects--Topical Terms:

1179695
Systematic biology.
Subjects--Index Terms:

Burn injuryIndex Terms--Genre/Form:

554714
Electronic books.

The Role of White Adipose Tissue Remodeling in Mediating Burn-Induced Hypermetabolism.
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