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Molecularly Distinct Sympathetic Populations Control Brown Adipose Tissue Functions
Molecularly Distinct Sympathetic Populations Control Brown Adipose Tissue Functions
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211153030
- ISBN
- 9798342761697
- DDC
- 616
- 저자명
- Neri, Daniele.
- 서명/저자
- Molecularly Distinct Sympathetic Populations Control Brown Adipose Tissue Functions
- 발행사항
- [Sl] : Columbia University, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 226 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 86-05, Section: B.
- 주기사항
- Advisor: Zeltser, Lori M.
- 학위논문주기
- Thesis (Ph.D.)--Columbia University, 2024.
- 초록/해제
- 요약Brown adipose tissue (BAT) serves as a crucial thermogenic organ, extracting glucose and lipids from circulation to generate heat. Enhancing BAT activity holds potential as a therapy for treating metabolic diseases, such as obesity and diabetes. The sympathetic nervous system (SNS) is the main regulator of BAT activity by increasing extraction and oxidation of substrates. However, the SNS role in metabolic disorders is complex. In obesity, there is increased sympathetic tone, yet reduced BAT responsiveness.Furthermore, increasing systemic sympathetic tone in individuals already at heightened cardiovascular risk leads to adverse complications, as demonstrated by recent clinical trials. As a result, BAT's impact on overall health in humans has been challenged in recent years, largely due to the lack of methods to selectively activate BAT without affecting other organs. Here, I used chemogenetics and retrograde viral injections in the interscapular BAT (iBAT) of mice to selectively activate only the neurons projecting to this tissue. Targeted activation of BAT did increase thermogenesis and improved glucose homeostasis.Leveraging on the single-cell RNA sequencing from our laboratory, we identified two sympathetic populations innervating iBAT: one primarily targets the small arterioles, while the other innervates the parenchyma. These populations mediate non-overlapping sympathetic-functions in iBAT: activating only the vascular projecting neurons lowers blood glucose without affecting thermogenesis, while activating the other population results in increased energy expenditure, local thermogenesis, and blood flow, with no effect on glycemia.The findings from this work could pave the way to the development of targeted strategies against metabolic disorders characterized by hyperglycemia, highlighting the potential of selectively activating specific SNS components to normalize blood glucose levels.
- 일반주제명
- Neurosciences
- 일반주제명
- Endocrinology
- 일반주제명
- Biology
- 일반주제명
- Cellular biology
- 키워드
- Glycemia
- 키워드
- Glucose
- 키워드
- Obesity
- 기타저자
- Columbia University Nutritional and Metabolic Biology
- 기본자료저록
- Dissertations Abstracts International. 86-05B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■00520250211153030
■006m o d
■007cr#unu||||||||
■020 ▼a9798342761697
■035 ▼a(MiAaPQ)AAI31635293
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a616
■1001 ▼aNeri, Daniele.
■24510▼aMolecularly Distinct Sympathetic Populations Control Brown Adipose Tissue Functions
■260 ▼a[Sl]▼bColumbia University▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a226 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 86-05, Section: B.
■500 ▼aAdvisor: Zeltser, Lori M.
■5021 ▼aThesis (Ph.D.)--Columbia University, 2024.
■520 ▼aBrown adipose tissue (BAT) serves as a crucial thermogenic organ, extracting glucose and lipids from circulation to generate heat. Enhancing BAT activity holds potential as a therapy for treating metabolic diseases, such as obesity and diabetes. The sympathetic nervous system (SNS) is the main regulator of BAT activity by increasing extraction and oxidation of substrates. However, the SNS role in metabolic disorders is complex. In obesity, there is increased sympathetic tone, yet reduced BAT responsiveness.Furthermore, increasing systemic sympathetic tone in individuals already at heightened cardiovascular risk leads to adverse complications, as demonstrated by recent clinical trials. As a result, BAT's impact on overall health in humans has been challenged in recent years, largely due to the lack of methods to selectively activate BAT without affecting other organs. Here, I used chemogenetics and retrograde viral injections in the interscapular BAT (iBAT) of mice to selectively activate only the neurons projecting to this tissue. Targeted activation of BAT did increase thermogenesis and improved glucose homeostasis.Leveraging on the single-cell RNA sequencing from our laboratory, we identified two sympathetic populations innervating iBAT: one primarily targets the small arterioles, while the other innervates the parenchyma. These populations mediate non-overlapping sympathetic-functions in iBAT: activating only the vascular projecting neurons lowers blood glucose without affecting thermogenesis, while activating the other population results in increased energy expenditure, local thermogenesis, and blood flow, with no effect on glycemia.The findings from this work could pave the way to the development of targeted strategies against metabolic disorders characterized by hyperglycemia, highlighting the potential of selectively activating specific SNS components to normalize blood glucose levels.
■590 ▼aSchool code: 0054.
■650 4▼aNeurosciences
■650 4▼aEndocrinology
■650 4▼aBiology
■650 4▼aCellular biology
■653 ▼aBrown adipose tissue
■653 ▼aGlycemia
■653 ▼aSympathetic nervous system
■653 ▼aGlucose
■653 ▼aObesity
■690 ▼a0317
■690 ▼a0409
■690 ▼a0306
■690 ▼a0379
■71020▼aColumbia University▼bNutritional and Metabolic Biology.
■7730 ▼tDissertations Abstracts International▼g86-05B.
■790 ▼a0054
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17164672▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
