Ignite Creation Date:
2024-06-16 @ 11:47 AM
Last Modification Date:
2024-10-26 @ 3:30 PM
Study NCT ID:
NCT06424132
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-05-21
First Post:
2024-05-10
Brief Title:
Thermogenic Silencer Regulatory Factors in Humans
Sponsor:
Rockefeller University
Organization:
Rockefeller University
Study Overview
Official Title:
Identification of Thermogenic Silencing Regulatory Factors as Biomarkers of Metabolic Health in Humans
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
A promising approach to correct the metabolic dysfunction associated with obesity is to activate brown fat non-shivering thermogenesis NST A critical limitation with NST as a therapeutic option however is that this beneficial process is silenced under human physiological temperature conditions and the mechanisms of how this occurs is unknown This study will be the first to identify human NST silencing factors that may be targeted for the treatment of obesity and metabolic disorders
Detailed Description:
Obesity and associated metabolic diseases such as type 2 diabetes continue to be one of the leading causes of death worldwide demanding additional research into novel treatments beyond our current options One promising experimental approach to overcome the metabolic dysfunctions associated with obesity such as insulin resistance and glucose imbalance is to activate brown fat non-shivering thermogenesis NST Activated human brown adipose tissue BAT increases energy expenditure at a molecular level and is associated with both improved insulin tolerance and glucose homeostasis A critical limitation with human brown fat as a therapeutic option however is that its beneficial metabolic potential is restricted in a silenced state under physiological temperature conditions for most of human life The regulatory factors that govern this silencing process are completely unknown While many groups continue to seek novel mechanisms to activate brown fat this study presents a unique approach aiming to decipher the mechanisms that govern human brown fat silencing The study hypothesizes that if the regulatory factors that silence brown fat NST can be defined then these factors can be targeted for ablation to eliminate the off switch thereby keeping brown fat in a constitutively active state Identification of human NST silencing factors will be critical to unlocking the metabolic benefits of human brown fat and would represent promising treatment opportunities for type 2 diabetes and other obesity-related disorders Understanding these relationships will allow for precision treatment opportunities for type 2 diabetes in the future
The overall goal of this study is to unlock the metabolic benefits of human brown fat by defining the regulatory mechanisms that keep BAT in a silenced state The study will generate the first human secretome list of secreted proteins in blood and transcriptome list of gene transcripts in adipose tissue compendium from human plasma and subcutaneous adipose tissue respectively which will be composed of target proteins metabolites and genes that are differentially expressed in response to NST silencing conditions Top candidates from the profiling will then be functionally validated in human adipocytes for their role in NST silencing The study will be an important resource for the field and will identify novel candidates that may harbor regulatory potential to govern the NST silencing process in humans These factors can then be targeted to promote the constitutive activation of NST in order to overcome the metabolic dysfunction associated with obesity and metabolic disease Given the invasive nature of direct human brown fat sampling the study will instead interrogate circulating factors in human plasma as a proxy for metabolic health In addition the study will also obtain subcutaneous adipose tissue for RNA profiling to identify genes that are upregulated under NST-silenced conditions compared to cold exposure
The overall goal of this study is to unlock the metabolic benefits of human brown fat by defining the regulatory mechanisms that keep BAT in a silenced state The study will generate the first human secretome list of secreted proteins in blood and transcriptome list of gene transcripts in adipose tissue compendium from human plasma and subcutaneous adipose tissue respectively which will be composed of target proteins metabolites and genes that are differentially expressed in response to NST silencing conditions Top candidates from the profiling will then be functionally validated in human adipocytes for their role in NST silencing The study will be an important resource for the field and will identify novel candidates that may harbor regulatory potential to govern the NST silencing process in humans These factors can then be targeted to promote the constitutive activation of NST in order to overcome the metabolic dysfunction associated with obesity and metabolic disease Given the invasive nature of direct human brown fat sampling the study will instead interrogate circulating factors in human plasma as a proxy for metabolic health In addition the study will also obtain subcutaneous adipose tissue for RNA profiling to identify genes that are upregulated under NST-silenced conditions compared to cold exposure
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None