# FSP27 regulation of vascular function in human obesity

> **NIH NIH K01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2021 · $134,741

## Abstract

Project Summary/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 vascular disease in human subjects. Adipose tissue
dysfunction, lipotoxicity, and insulin resistance are essential abnormalities linking obesity to the
pathogenesis of cardiovascular disease. This proposal will employ a number of complementary
approaches harnessing physiological studies of vascular endothelial vasodilator function and
angiogenesis, pharmacological and biological methods to probe dysfunctional signaling pathways, and
proteomics-based approaches to gain novel insight into the role of a newly identified protein FSP27 in
the pathogenesis of vascular disease in obesity. In aim1, we will investigate the role of FSP27 in depot-
specific mechanisms of vascular dysfunction in the human adipose tissue microenvironment, using
videomicroscopy and angiogenic assays to examine microvascular responses in both subcutaneous
and visceral adipose compartments biopsied during elective surgical procedures, including bariatric
surgery, in 150 obese and 50 lean subjects. We will characterize vascular phenotypes in relation to
FSP27 signaling and test the hypothesis that down-regulation of FSP27 is linked to insulin resistance
and vascular dysfunction. In aim 2, we will seek to identify molecular mechanisms that contribute to
FSP27 regulation of vascular function by employing proteomics-based approaches using mass
spectrometry to identify proteins and subsequent pathways differentially modulated by FSP27 in
relevance to lipotoxicity, insulin resistance, and vascular biology. In aim 3, vascular studies, metabolic
phenotyping, and proteomics will be repeated at 6-months following bariatric surgical intervention in the
same 150 obese subjects from aims 1 and 2. We will test whether relevant FSP27-related molecular
pathways identified in aim 2 are influenced by marked weight loss and/or metabolic changes and
hypothesize that weight loss will improve vascular phenotype and linked to FSP27 signaling. The
overall project will combine molecular biology with human physiology in severely obese individuals
where clinically very little vascular data currently exist. The long-term goal of the applicant is to develop
an academic career in the field of obesity and cardiovascular disease, and this proposal will allow the
applicant to expand her translational expertise 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 cr...

## Key facts

- **NIH application ID:** 10183236
- **Project number:** 5K01DK114897-04
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Shakun Karki
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $134,741
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10183236

## Citation

> US National Institutes of Health, RePORTER application 10183236, FSP27 regulation of vascular function in human obesity (5K01DK114897-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10183236. Licensed CC0.

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