P311 mediated adipogenesis, adipocyte plasticity and metabolic regulation

P311 介导的脂肪生成、脂肪细胞可塑性和代谢调节

基本信息

  • 批准号:
    10631036
  • 负责人:
  • 金额:
    $ 35.5万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-06-01 至 2026-05-31
  • 项目状态:
    未结题

项目摘要

Summary One third of the US population is clinically obese, a condition which increases the risk for chronic diseases like type 2 diabetes mellitus (DM), heart disease and cancers. Adipocyte dysfunction (AD) is cardinal feature of metabolic dysregulation and increases the risk for developing insulin resistance (IR), DM, and hypertension. Along with adipocyte hypertrophy, macrophage infiltration of white adipose tissue (WAT) is associated with the pathophysiology of obesity, AD and IR, albeit the underlying molecular mechanisms are uncharacterized. We were first to show the presence of P311 in WAT, brown adipose tissue (BAT) and beige adipose tissue. The WAT of P311 knockout (KO) mice has fewer resident macrophages and decreased cellular dynamics, including decreased autophagy and apoptosis. This is potentially leading to adipocyte hypertrophy that in turn causes hyperglycemia due to age- and genetic ablation-mediated P311 expression leading to overworked and exhausted adipocytes in P311 KOs or low P311 expressing adipocytes compared to wild types. As studies are limited, resident macrophages could alter adipocyte function early in adipose tissue development, a novel mechanism requiring exploration. We will also explore key adipocyte cellular processes of apoptosis and autophagy/lipophagy, which may affect adipocyte turnover in the WAT of P311 KO mice, leading to adipocyte hypertrophy and dysfunction, and thus metabolic deregulation. The proposed project will test the central hypothesis that age- and genetic ablation-mediated P311 levels play a key role in white, brown and beige adipocyte development, plasticity and function, as well as in metabolic regulation. Further, we will investigate the role of P311 in cellular processes (i.e., WAT browning and BAT whitening) and its effect on adipocyte function and glycemic control, as P311 KO mice are hyperglycemic. We will also evaluate the ability of P311 to modulate adipose biology and metabolic regulation through PPAR and UCP1 regulation; and myo1C binding to GLUT4. We will develop adipocyte-specific P311 KO conditional mice using novel CRISPR technology to evaluate the adipocyte-specific P311 roles. The current project will thereby establish P311 as a new player in adipocyte biology and metabolic regulation. Our experimental strategy will incorporate transgenic animals using classic cell biology, molecular biology, biochemical, immunoassays and imaging methods studies. Our findings will enhance the understanding of P311 mediated fat cell development and function and fat mass expansion. Our ongoing studies indicate that P311 potentially regulates metabolism through adipocyte dynamics, function and plasticity (a novel approach to targeting metabolic disorders through browning of WAT); regulating resident and infiltrating macrophages; and controlling adipocyte cellular processes. These studies are new and do not overlap with existing funding.
总结

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Kameswara Rao Badri其他文献

Kameswara Rao Badri的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Kameswara Rao Badri', 18)}}的其他基金

P311 mediated adipogenesis, adipocyte plasticity and metabolic regulation
P311 介导的脂肪生成、脂肪细胞可塑性和代谢调节
  • 批准号:
    10334071
  • 财政年份:
    2022
  • 资助金额:
    $ 35.5万
  • 项目类别:

相似国自然基金

相似海外基金

Recruitment of brown adipocytes in visceral white adipose tissue by fibroblast growth factor 8b
成纤维细胞生长因子 8b 将棕色脂肪细胞募集到内脏白色脂肪组织中
  • 批准号:
    321208980
  • 财政年份:
    2016
  • 资助金额:
    $ 35.5万
  • 项目类别:
    Research Grants
Enhancing Energy Expending Adipocytes in White Adipose Tissue
增强白色脂肪组织中的能量消耗脂肪细胞
  • 批准号:
    8827438
  • 财政年份:
    2014
  • 资助金额:
    $ 35.5万
  • 项目类别:
Induction of brown-like adipocytes in white adipose tissue by food-derived factors
食物源性因子在白色脂肪组织中诱导棕色样脂肪细胞
  • 批准号:
    26450168
  • 财政年份:
    2014
  • 资助金额:
    $ 35.5万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
WAT-on-a-chip - Development of a micofluidic, microphysiologic in vitro adipose tissue model for high-throughput drug screening based on hiPSC-derived adipocytes.
WAT-on-a-chip - 开发微流体、微生理体外脂肪组织模型,用于基于 hiPSC 衍生脂肪细胞的高通量药物筛选。
  • 批准号:
    257256526
  • 财政年份:
    2014
  • 资助金额:
    $ 35.5万
  • 项目类别:
    Research Fellowships
Enhancing Energy Expending Adipocytes in White Adipose Tissue
增强白色脂肪组织中的能量消耗脂肪细胞
  • 批准号:
    8828181
  • 财政年份:
    2013
  • 资助金额:
    $ 35.5万
  • 项目类别:
Enhancing Energy Expending Adipocytes in White Adipose Tissue
增强白色脂肪组织中的能量消耗脂肪细胞
  • 批准号:
    8520690
  • 财政年份:
    2013
  • 资助金额:
    $ 35.5万
  • 项目类别:
Enhancing Energy Expending Adipocytes in White Adipose Tissue
增强白色脂肪组织中的能量消耗脂肪细胞
  • 批准号:
    8629741
  • 财政年份:
    2013
  • 资助金额:
    $ 35.5万
  • 项目类别:
Effect of exercise training on formation of brite adipocytes within white adipose tissue
运动训练对白色脂肪组织内脂肪细胞形成的影响
  • 批准号:
    23700778
  • 财政年份:
    2011
  • 资助金额:
    $ 35.5万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Investigation for the mechanisms of the emergence of brown adipocytes in white adipose tissue
白色脂肪组织中棕色脂肪细胞出现机制的研究
  • 批准号:
    21780261
  • 财政年份:
    2009
  • 资助金额:
    $ 35.5万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
LOUISIANA COBRE: P1: INDUCE THERMOGENIC BROWN ADIPOCYTES IN WHITE ADIPOSE TISSUE
路易斯安那 COBRE:P1:在白色脂肪组织中诱导产热棕色脂肪细胞
  • 批准号:
    7610781
  • 财政年份:
    2007
  • 资助金额:
    $ 35.5万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了