课题基金 / 基金详情

Molecular Mechanism of Brown Adipose Tissue Regression

Molecular Mechanism of Brown Adipose Tissue Regression
棕色脂肪组织消退的分子机制
批准号:
10571698
负责人:
Daorong Feng
金额:
$57.81万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
未结题
起止时间:
2021-04-15 至 2025-02-28

项目摘要

项目成果

Daorong Feng的其他基金

相似基金

相关文献

中文摘要
翻译
摘要
英文摘要
Abstract Our preliminary data demonstrates that in both Adipoq and UCP1-specific Stx4 knockout mice results in the activation of pyroptotic brown adipocyte cell death through the NLRP1 (NOD-like receptor protein 1) signaling pathway. In parallel, brown adipose function and to a lesser extent mass declines during aging and this age-associated decline in BAT thermogenesis occur concomitant with the induction of pyroptosis. Furthermore, in both modes the regression of BAT results in the reduction in insulin sensitivity, energy expenditure and cold tolerance that can be reversed by over expression of Stx4 in brown/beige adipocytes (UCP1-Stx4 transgenic mice) or by blocking of pyroptosis using an inhibitor of caspase 1. In addition, aged and Stx4 knockout mice have reduced protein levels of the cell survival receptors Ntrk3, a brown adipocyte selective tyrosine receptor kinase within brown adipose tissue. Based upon these data, we are proposing a multi-principal investigator (MPI) application to understand the molecular basis for the decline in brown adipose tissue mass and function during the normal development of aging and the functional/physiological consequences of preserving brown mass and function, in terms of energy balance, insulin sensitivity and metabolic homeostasis. In this proposal, we will determine 1) the specific pathways and signaling events responsible for brown adipocyte pyroptosis and functional consequences of preserving BAT using both pharmacological and genetic interventions; 2) the functional role of the neurotropic tyrosine receptor kinase Ntrk3 in regulating BAT mass, function and brown adipocyte pyroptosis; and 3) changes in tissue cellular identity and its role during age-dependent BAT dysfunction and regression. The findings obtained from this proposal will then allow to develop strategies to prevent age-dependent regression of BAT that will likely provide a more tractable and effective therapeutic approach than the induction of beige adipose tissue to improve glucose metabolism, increase energy expenditure and prevent weight gain.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Molecular Mechanism of Brown Adipose Tissue Regression
Molecular Mechanism of Brown Adipose Tissue Regression
国内基金
海外基金
支链氨基酸代谢紊乱调控“Adipocytes - Macrophages Crosstalk”诱发2型糖尿病脂肪组织功能和结构障碍的作用及机制