- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04206124
mTORC1 and Autophagy in Human Brown Adipocytes (mTORHBFC)
Regulation of Beige Fat Development by mTORC1 and Autophagy
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Specific Aim 1: To investigate the role of mTORC1 and autophagy in regulating thermogenesis in human brown adipocytes. The working hypothesis is that inhibition of mTORC1 or activation of autophagy improves thermogenesis in human brown adipocytes. It will be first determined if the mTORC1/autophagy signaling modulates thermogenic gene expression and beige markers by collecting human brown fat from lean non-diabetic subjects. The brown fat during the anterior cervical spine surgery or thyroidectomy from lean subjects with a BMI <25, or obese participants who have a BMI >30, will be harvested and then be used to determine: 1) whether mTORC1 signaling, autophagy and thermogenic gene expression, and the fraction of various types of immune cells in human brown fat are different from those in rodents;2) whether rapamycin treatment enhances basal or CL-induced thermogenic gene expression and O2 consumption in primary human brown adipocytes; and 3) whether inhibition of autophagy by 3-methyladenine (3-MA) suppresses thermogenic gene expression induced by CL316,243, a β3-adrenoceptor agonist that mimics cold stress in vivo in human brown adipocytes.
Overall, this study will lead to the identification of mTORC1 as a key regulator of thermogenesis in human adipose tissue and reveal promising new anti-obesity drug targets. In addition, this study will further investigate the role of rapamycin administration in obesity in human adults near the future. These studies are designed to be a proof-of-principle. If the results are promising, then future drug development could focus on designing new inhibitors of mTORC1.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Meilian Liu, PhD
- Phone Number: 5052724036
- Email: meilianliu@salud.unm.edu
Study Contact Backup
- Name: Lily Elizabeth Feldman
- Phone Number: 8025223687
- Email: feldman.lily@gmail.com
Study Locations
-
-
New Mexico
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Albuquerque, New Mexico, United States, 87131
- University of New Mexico Health Sciences Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Male or Female
- age 18-60
- able to give informed consent
- non-diabetic
- scheduled for anterior cervical spine, thyroidectomy, or parathyroidectomy surgery at UNMHSC
- BMI <25 (lean) or >30 (obese)
- English or Spanish speaking
Exclusion Criteria:
- has diabetes mellitus (type I or II)
- currently on any study medication (including sedatives or analgesics, coagulopathy (INR of 1.5 or greater, platelet count of <50,000/microliter), or anticoagulant)
- pregnant
- incarcerated
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Single Arm Study Group
Includes all consented patients, male and female, undergoing anterior cervical spine surgery, parathyroidectomy or thyroidectomy (18-60 years old), without history of diabetes mellitus and not pregnant or incarcerated.
|
During previously indicated thyroid gland removal or anterior cervical spine surgery, as scheduled at UNMHSC, the surgeon will identify the large muscle on the side of the neck in the surgical field.
Using minimal dissection adjacent to the muscle, they will then remove 5-10mg of brown fat from this region.
These samples will be further analyzed using various biochemical tools.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Protein expression levels in lean and obese human brown adipose tissue samples will be quantified via Western Blot and comparatively analyzed using a student T-test.
Time Frame: Up to six years after date of sample collection.
|
Human brown adipose tissue (BAT) samples will be collected during previously scheduled anterior neck surgery and then cultured and amplified for experiments including Western Blot (WB), an assay to quantify the relative amounts of protein present in a sample. WB will be used to determine how protein expression levels differ between lean and obese BAT samples. Specifically, the translational levels of key markers of mTOR signaling including UCP1, C/EBPβ, HSL, S6K, ADPN, PKA, AMPK and ATGL will be quantified by WB and analyzed statistically using student T-test, and protein activation levels will be quantified by dividing phosphorylated protein content by total protein content. |
Up to six years after date of sample collection.
|
Gene transcript expression levels in lean and obese human brown adipose tissue samples will be quantified via quantitative Polymerase Chain Reaction and comparatively analyzed using a student T-test.
Time Frame: Up to six years after date of sample collection.
|
Human brown adipose tissue (BAT) samples will be collected during previously scheduled anterior neck surgery and then cultured and amplified for experiments including quantitative-Polymerase Chain Reaction (q-PCR), an assay to quantify the relative amounts of mRNA (transcribed genes) present in a sample. q-PCR will be used to determine how gene expression levels differ between lean and obese BAT samples. Specifically, the transcriptional levels of key markers of mTOR signaling including UCP1, C/EBPβ, HSL, S6K, ADPN, PKA, AMPK and ATGL will be quantified by q-PCR and analyzed using student T-test. |
Up to six years after date of sample collection.
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Meilian Liu, PhD, University of New Mexico Biochemistry & Molecular Biology
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 14-272
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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