# The Importance of the Batf3/Irf4 Pathway in Growth Hormone and Inflammation Mediated Metabolic Changes in Adipose Tissue

> **NIH NIH F32** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $78,558

## Abstract

The growth hormone receptor (GHR) is part of a highly conserved set of receptors known as the type I cytokine
family. GHR is homologous to many receptors involved in inflammation and host defense including the
interleukin-2, interleukin-6 and colony stimulating family of receptors. They share many downstream signaling
mechanisms including the Janus kinase (JAK)/ signal transducer and activator of transcription (STAT)
mechanism of inducing transcriptional regulation of target genes. Growth hormone (GH), a pituitary-derived
hormone best known for its role in growth and development, also serves important metabolic functions including
mediating lipolysis in adipose tissue during periods of starvation. The precise mechanism by which the JAK/
STAT pathway activation promotes lipolysis in response to GH has yet to be elucidated. Our preliminary data
has shown that growth hormone stimulation of adipose tissue leads to the transcriptional upregulation of the
basic leucine zipper transcription factor ATF-like 3 (Batf3) gene. This gene is a known response element in the
promotion of dendritic cell development and cytotoxic T-cell function in response to pathogens. It is also known
to associate with interferon regulatory factors, such as interferon regulatory factor 4 (Irf4) as heterodimers to
promote proliferative gene expression in context of inflammatory signals. Recent work has also shown that Irf4
is a key transcription factor in adipose tissue that drives thermogenesis and lipolysis. We have identified that Irf4
transcripts are also induced during GH stimulation. We hypothesize that the Batf3/Irf4 signaling mechanism is
conserved in the growth hormone pathway and is important in driving lipolysis, altering mitochondrial respiration
and affecting IGF-1/insulin signaling. We will address our hypothesis by performing functional genomics on
adipose tissue both in vivo and in vitro. The metabolic consequences of Batf3 and Irf4 induction will be examined
by disrupting these genes in adipocytes using CRISPR-based approaches and adipocyte-specific knockout mice.
We will examine adipose tissue for lipolytic capacity, body composition and respiratory dynamics to determine
the metabolic importance of the Batf3/Irf4 system in adipose tissue under both growth hormone and
lipopolysaccharide (LPS) signaling. The goal of these studies is to prove the importance of evolutionarily
conserved inflammatory signaling cascades in altering metabolism.

## Key facts

- **NIH application ID:** 10141377
- **Project number:** 1F32DK124948-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Armen I Yerevanian
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $78,558
- **Award type:** 1
- **Project period:** 2020-09-23 → 2022-09-22

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10141377

## Citation

> US National Institutes of Health, RePORTER application 10141377, The Importance of the Batf3/Irf4 Pathway in Growth Hormone and Inflammation Mediated Metabolic Changes in Adipose Tissue (1F32DK124948-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10141377. Licensed CC0.

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