# Role of STAT3 in sepsis-induced adipose tissue browning and the impact of obesity

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2020 · $318,000

## Abstract

Project Summary
Obesity is a significant public health problem with an increasing prevalence in both adults and children. Obesity
increases the risk for many comorbid disorders including sepsis and for sepsis-related complications. It is now
well established that obesity is associated with a state of chronic systemic inflammation because many cells
within adipose tissue have inflammatory properties. Critical illness is associated with adipose tissue remodeling
and occurs even in the absence of obesity. There are two functionally and histologically different types of
adipose tissue: white adipose tissue (WAT) and brown adipose tissue (BAT). WAT takes on a BAT phenotype
in response to stressful stimuli (cold stress, burn injury), a process known as browning, and is characterized by
an increase in uncoupling protein (UCP)-1. In BAT UCP1 is important for thermogenesis. Browning increases
energy expenditure and oxygen consumption, confers protection from obesity and improves insulin sensitivity.
Signal transducer and activator of transcription (STAT3) is an important acute phase reactant in sepsis that
also affects lipolysis so may be an important regulator of browning. The effect of obesity on the adipose tissue
response to sepsis-induced critical illness has not been well explored. Data from our laboratory suggest that
adipose tissue browning occurs in non-obese mice after polymicrobial sepsis but is impaired in obese mice.
The long-term goal of our studies is to understand the mechanisms through which body fat, in normal and in
excess, contributes to the altered immune response in sepsis-induced critical illness. The central hypothesis
of our proposal is that during sepsis adipose tissue undergoes phenotypical and functional changes that
facilitates recovery but this process is impaired in obesity. We plan to test our hypothesis and accomplish the
objectives by completing the following three specific aims. In Aim 1 we will determine the functional
contribution of adipose tissue in recovery during sepsis in obese and non-obese mice. In Aim 2 we will
determine the contribution of STAT3 to the inflammatory and metabolic responses in obese and non-obese
mice during sepsis. In Aim 3 we will determine whether adipose tissue from obese and non-obese children
undergoes phenotypic changes consistent with browning during ex vivo endotoxin stimulation. The role that
adipose tissue contributes to the systemic inflammatory response in obesity and in the absence of obesity
during critical illness has not been explored and is the focus of our investigations. This is significant because
understanding the mechanistic changes that occur in adipose tissue that can affect obese and non-obese
subjects can lead to improved therapies for patients.

## Key facts

- **NIH application ID:** 9983723
- **Project number:** 5R01GM126551-04
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Jennifer Melissa Kaplan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $318,000
- **Award type:** 5
- **Project period:** 2017-09-25 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983723

## Citation

> US National Institutes of Health, RePORTER application 9983723, Role of STAT3 in sepsis-induced adipose tissue browning and the impact of obesity (5R01GM126551-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9983723. Licensed CC0.

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