東華大學圖書館 |

Language: English

Help

回圖書館首頁

手機版館藏查詢

Back

Switch To: Labeled | MARC Mode | ISBD

The Role of White Adipose Tissue Rem...

Knuth, Carly Michelle.

Linked to FindBook

Google Book

Amazon

博客來

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

Record Type:	Electronic resources : Monograph/item
Title/Author:	The Role of White Adipose Tissue Remodeling in Mediating Burn-Induced Hypermetabolism./
Author:	Knuth, Carly Michelle.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2023,
Description:	176 p.
Notes:	Source: Dissertations Abstracts International, Volume: 85-05, Section: B.
Contained By:	Dissertations Abstracts International85-05B.
Subject:	Systematic biology. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30493887
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. - Ann Arbor : ProQuest Dissertations & Theses, 2023 - 176 p.

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

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

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.

ISBN: 9798380840316Subjects--Topical Terms:

3173492
Systematic biology.
Subjects--Index Terms:

Burn injury

The Role of White Adipose Tissue Remodeling in Mediating Burn-Induced Hypermetabolism.
LDR:03761nmm a2200385 4500 001 2401073
005 20241015112515.5
006 m o d
007 cr#unu||||||||
008 251215s2023 ||||||||||||||||| ||eng d
020 $a 9798380840316
035 $a (MiAaPQ)AAI30493887
035 $a AAI30493887
035 $a 2401073
040 $a MiAaPQ $c MiAaPQ
100 1 $a Knuth, Carly Michelle. $3 3771135
245 1 0 $a The Role of White Adipose Tissue Remodeling in Mediating Burn-Induced Hypermetabolism.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2023
300 $a 176 p.
500 $a Source: Dissertations Abstracts International, Volume: 85-05, Section: B.
500 $a Advisor: Jeschke, Marc;Screaton, Rob.
502 $a Thesis (Ph.D.)--University of Toronto (Canada), 2023.
520 $a 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.
590 $a School code: 0779.
650 4 $a Systematic biology. $3 3173492
650 4 $a Medicine. $3 641104
650 4 $a Cellular biology. $3 3172791
653 $a Burn injury
653 $a Hypermetabolism
653 $a White adipose tissue
653 $a Hypermetabolic response
690 $a 0423
690 $a 0564
690 $a 0379
710 2 $a University of Toronto (Canada). $b Medical Science. $3 3182952
773 0 $t Dissertations Abstracts International $g 85-05B.
790 $a 0779
791 $a Ph.D.
792 $a 2023
793 $a English
856 4 0 $u https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30493887