# Adipose stem cells niche in obesity

> **NIH VA I01** · JAMES A. HALEY VA MEDICAL CENTER · 2020 · —

## Abstract

Obesity continues to escalate as a significant public health problem and as the leading preventable
cause of death. One third of adult population in US is obese (CDC's BRFSS, 2015). Alarmingly, 78%
of the veteran population is obese, a notably higher percent compared to general population. With
over 9.2 million beneficiaries, the cost of obesity and its related diseases exceeds $1.7 billion
annually for the VA (18). With this significant rising epidemic, obesity has become one of the major
health risk factor that contributes to the development of severe conditions such as cardiovascular
diseases, diabetes mellitus, stroke and certain cancers.
Genetic, environmental, behavioral, and socioeconomic factors cause excess weight gain and
obesity. Adipose tissue is an important endocrine regulator of energy homeostasis and glucose
metabolism. New adipocytes are required for storage of excess energy (intake>expenditure) in the
white adipocyte tissue and this is accomplished via adipose stem cells' adipogenesis process. Using
human adipose stem cells (ASC) from lean and obese patients, it was showed that adipogenesis is
dysregulated in obesity and mature adipocytes in obese subjects show distinctive phenotype
compared to lean subjects(5, 6). Obesity is accompanied with chronic low grade inflammation which
initiates insulin resistance and metabolic syndrome(7, 8). It was demonstrated that obesity changes
the adipose stem cell niche. However, the impact of this phenomenon and importance of ASC niche
in obesity has not been investigated mechanistically. Hence, a screening study was undertaken to
identify genes whose expression is altered in obese ASC such that it renders adipocytes susceptible
to increased inflammation. Data showed increase of Protein Kinase C deltaI (PKCδI) -an important
kinase in cellular differentiation, proliferation and apoptosis. The data indicated that PKCδI promotes
inflammation in obese adipocytes. Based on these observations, the goal is to elucidate the role of
PKCδI in adipose stem cells in obesity.
Aim 1: Determine the role of PKCδI in promoting inflammation in obesity: Obesity associated
inflammation contributes to insulin resistance and metabolic syndrome. Data showed that PKCδI is
increased in obesity and PKCδI knockdown inhibits inflammation in obese ASC. Systematic
analysis of inflammatory genes with gain and loss of PKCδI will be performed. Aim 2: Determine
the regulation of PKCδI expression in obese ASC. Using ASC, the data shows that NEAT1, a
long noncoding RNA, regulates PKCδI expression. The molecular mechanisms underlying
regulation of PKCδI expression by NEAT1 will be determined using RNA binding assays and
loss/gain of function studies in ASC. Aim 3: Develop and validate a novel, specific PKCδI
inhibitor in obesity in vivo. PKCδI is increased in obese adipocytes and it mediates inflammation
which culminates in insulin resistance in obesity. Silencing PKCδI decreases apoptosis and
inflammation in obese adipocytes. Th...

## Key facts

- **NIH application ID:** 9898248
- **Project number:** 5I01BX003836-04
- **Recipient organization:** JAMES A. HALEY VA MEDICAL CENTER
- **Principal Investigator:** Niketa A. Patel
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-04-01 → 2021-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9898248

## Citation

> US National Institutes of Health, RePORTER application 9898248, Adipose stem cells niche in obesity (5I01BX003836-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9898248. Licensed CC0.

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