# Hypothalamic NF-kB and astrocytic programs in obesity

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2021 · $523,420

## Abstract

ABSTRACT/SUMMARY
Having appreciated the role of pro-inflammatory IKKβ/NF-κB pathway in the hypothalamic mechanism of
obesity, the objective of this research is to study how hypothalamic neurons and astrocytes are
programmatically involved. Through recent studies including preliminary experiments on mice with
hypothalamic astrocytic IKKβ/NF-κB activation or inhibition, supportive evidence was obtained to suggest that
astrocytes in the mediobasal hypothalamus (MBH) have multiple programs through IKKβ/NF-κB for being
responsible for metabolic imbalance. Hence, the hypothesis of this proposal is, sustained activation of
astrocytic IKKβ/NF-κB in the MBH under chronic high-fat diet feeding leads to altered astrocyte-neuron
relationships in the MBH, at least due to an impairment in astrocyte-dependent GABA clearance and also an
enhancement in astrocytic cytokine production – which employ GABA and cytokine receptor signaling to
influence the responsible neurons, resulting in multiple forms of neuronal dysregulation on metabolic balance
which underlie obesity and pre-diabetic development. Three Aims are designed to study (1) astrocytic
IKKβ/NF-κB–autophagy axis in linking hypothalamic neurons to metabolic dysregulation, (2) IKKβ/NF-κB-
dependent astrocytic clearance of GABA in linking POMC neuronal inhibition to obesity, and (3) IKKβ/NF-κB-
driven astrocytic cytokines in linking other responsive hypothalamic neurons to disease development. A
combination of cellular, molecular, genetic, physiological and pharmacological approaches will be used to
analyze astrocytic biology and functions, the overall and local influences on neurons, and their mechanistic
roles for obesity and pre-diabetes. Successful completion of this project will be important for understanding the
hypothalamic basis of obesity and diabetes and provide new paradigms in designing interventional strategies.

## Key facts

- **NIH application ID:** 10135686
- **Project number:** 5R01DK121435-03
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Dongsheng Cai
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $523,420
- **Award type:** 5
- **Project period:** 2019-06-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135686

## Citation

> US National Institutes of Health, RePORTER application 10135686, Hypothalamic NF-kB and astrocytic programs in obesity (5R01DK121435-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10135686. Licensed CC0.

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