# Determinants of obesity-associated insulin resistance

> **NIH NIH K23** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2020 · $170,478

## Abstract

This proposal describes a 5-year training program that will expand the applicant's scientific knowledge,
advance her expertise in patient-oriented translational research, and establish independence from her
primary mentor. A 4-member Mentoring Team and 3-member Advisory Committee will oversee her
training and career development. The current application represents a patient-oriented clinical proposal
that examines mechanisms of obesity-associated insulin resistance in human subjects. Obesity has
emerged as one of the most critical health care problems in the US. Adipose tissue dysfunction and
inflammation are essential hallmarks linking obesity to the pathogenesis of cardiometabolic disease.
The proposal will employ a number of complementary approaches harnessing physiological studies of
vascular endothelial function, pharmacological and biological methods to probe dysfunctional insulin
signaling pathways in fat tissue, immunohistochemical techniques for adipose phenotyping, and
computed tomography (CT) imaging of human fat to gain novel insight into pathogenic disease
mechanisms. In aim 1, she will examine insulin-mediated vasodilator responses using videomicroscopy
of arterioles isolated from subcutaneous and two separate visceral adipose depots biopsied during
planned bariatric surgery in 200 obese subjects, and probe the functional significance of Wnt-pathway
signaling in the regulation of vascular insulin resistance. Aim 2 will utilize abdominal CT imaging to
identify quantitative and qualitative depot-specific adipose tissue parameters linked to insulin resistance
and vascular dysfunction. CT findings will be compared to the histoarchitecture of adipose tissue
samples biopsied in aim 1 that will provide a defined basis for correlating imaging study findings with
histopathological and molecular processes at the tissue level that may provide novel clues to disease
mechanisms. Aim 3 will repeat studies of vascular endothelial function, metabolic profiling, CT imaging
and adipose tissue biopsies 6-months after bariatric surgical intervention in the same 200 obese
subjects from aim 1. The applicant will examine how relevant and interlinked relationships that govern
insulin resistance and vascular dysfunction identified in aims 1 and 2 are influenced by marked weight
reduction in severely obese individuals where very little information currently exists. The long-term goal
of the applicant is to develop an academic career as a clinical scientist in the field of obesity and
cardiovascular disease. This proposal will allow the applicant to expand her translational research
expertise and mature her patient-oriented research in an area that is relatively unexplored and
medically important. Obesity will remain one of the most important health care challenges worldwide,
and improving our understanding of mechanisms of obesity-related cardiovascular disease is critical.

## Key facts

- **NIH application ID:** 9853834
- **Project number:** 5K23HL135394-04
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Melissa G Farb
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $170,478
- **Award type:** 5
- **Project period:** 2017-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853834

## Citation

> US National Institutes of Health, RePORTER application 9853834, Determinants of obesity-associated insulin resistance (5K23HL135394-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9853834. Licensed CC0.

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