mTORC1 and Autophagy in Human Brown Adipocytes

NCT04206124 | Completed DMC

• 1 other identifier: 14-272
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The long term goal is to identify the potential therapeutic targets for the treatment of obesity and its associated disorders by studying the driving factors of activation of brown adipose tissue (BAT) in human adults. Whereas activation of brown adipose tissue (BAT) in human adults has been considered as a potential therapeutic target to battle obesity since it was identified in 2009, the underlying mechanisms of beige adipocytes appearance in human adults is unclear. The objective of this proposal is to investigate the role of autophagy in mediating the inhibitory effect of mammalian target of rapamycin complex 1 (mTORC1) in regulating human brown adipocytes. The central hypothesis is that autophagy plays a critical role in regulating browning of white adipose tissue and mediates the beneficial effect of mTORC1 inhibition on thermogenesis in human brown adipocytes.

Conditions

Obesity; Metabolic Disease

Keywords

Autophagy; Inflammation; Metabolism; Adipocyte; mTORC1; Obesity; Thermogenesis

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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.

Study Arms (1)

Single Arm Study Group

EXPERIMENTAL

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.

Procedure: Brown Fat Harvest During Anterior Neck Surgery

Interventions

Brown Fat Harvest During Anterior Neck Surgery PROCEDURE

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.

Single Arm Study Group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of New Mexico: lead

Study Sites (1)

University of New Mexico Health Sciences Center

Albuquerque, New Mexico, 87131, United States

Location

MeSH Terms

Conditions

Obesity; Metabolic Diseases; Inflammation

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes

Study Officials

• Meilian Liu, PhD

  University of New Mexico Biochemistry & Molecular Biology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Patients will be recruited based on sex, age, and medical history including BMI (lean, \<25, or obese, \>30), medication list, and health status. Included patients indicated for thyroidectomy, parathyroidectomy, or cervical spine injury surgery, who are able to consent, will have a soybean-sized amount of brown fat removed from the neck during surgery. These tissue samples will be further analyzed using biochemical tools after being de-identified from patient records.

Study Record Dates

• First Submitted: December 13, 2019
• First Posted: December 20, 2019
• Study Start: November 1, 2016
• Primary Completion: September 30, 2020
• Study Completion: September 30, 2020
• Last Updated: October 22, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)