Ancient Neuropeptide FAM237B Discovered in Hunger Neurons — Regulated by Fasting and Inflammation | Research

The takeaway

FAM237B is an evolutionarily conserved orexigenic micropeptide in AgRP/NPY neurons, regulated by fasting (up) and insulin (down, PI3K-dependent), with expression also induced by pro-inflammatory stimuli.

Ancient hunger peptide
FAM237B is conserved from jawless vertebrates and may predate AgRP itself in the evolution of the hunger signaling system

What the researchers found

FAM237B: conserved micropeptide in AgRP/NPY neurons; expression rises with fasting, suppressed by insulin (PI3K-dependent), and upregulated by pro-inflammatory stimuli (LPS, IL-6, TNF-α).

Why it matters

A new orexigenic peptide in the hunger circuitry that responds to both metabolism and inflammation could explain obesity-inflammation connections and reveal new drug targets.

How the study worked

Comparative genomics/synteny, single-cell and bulk RNA-seq in mouse arcuate, hypothalamic cell models, primary hypothalamic cultures, fasting/feeding experiments, and signaling pathway studies.

What this study cannot tell us

Function not directly tested (no feeding studies with FAM237B administration). Mouse data; human hypothalamic expression lower. Processing from prohormone not confirmed.

How to read the evidence

Discovery study with comprehensive evolutionary, transcriptomic, and regulatory characterization. Functional feeding studies pending.

When this study was published

Published in 2025.

The bigger picture

FAM237B may be older than AgRP itself. Its discovery adds a new component to the hypothalamic hunger circuit and connects appetite to neuroinflammation.

Questions still open

Does exogenous FAM237B increase food intake?
Is FAM237B a therapeutic target for obesity?
Does FAM237B contribute to inflammation-driven cachexia or obesity?

Common questions

What is FAM237B?

A newly discovered tiny protein (micropeptide) in the brain's hunger neurons. It was previously thought to be junk RNA, but is actually an ancient appetite-regulating peptide conserved across 500 million years of evolution.

Why does inflammation increase a hunger peptide?

When the body is inflamed, FAM237B levels rise in hunger neurons. This connection between inflammation and appetite may help explain why infections cause changes in eating behavior and why obesity involves brain inflammation.

Read the original research

FAM237B, a conserved orexigenic neuropeptide, is regulated by fasting, insulin, and neuroinflammation in mouse hypothalamic NPY/AgRP neurons.

Molecular and cellular endocrinology, 112773

View on PubMed ↗Publisher’s paper ↗

Citation

He, Wenyuan; McIlwraith, Emma K; Belsham, Denise D. (2026). FAM237B, a conserved orexigenic neuropeptide, is regulated by fasting, insulin, and neuroinflammation in mouse hypothalamic NPY/AgRP neurons.. Molecular and cellular endocrinology, 112773. https://doi.org/10.1016/j.mce.2026.112773