# The Role of Mediobasal Hypothalamic Gliosis in Gestational Weight Gain and Gestational Visceral Fat Accretion

> **NIH NIH R21** · EMORY UNIVERSITY · 2023 · $448,441

## Abstract

PROJECT SUMMARY
 Pregnancy is a unique state in which maternal gestational weight gain (GWG) is physiologically adaptive
and necessary. Excessive gestational weight gain (EGWG) is weight gain exceeding guidelines and contributes
to long term maternal metabolic dysfunction. While many diet- and activity-based intervention trials have been
performed to limit EGWG, the data are inconsistent regarding successfully preventing EGWG in pregnancy.
Potentially, the impediments faced in successfully mitigating EGWG arise from our lack of clarity about
mechanisms underlying physiologic GWG. Therefore, the concept that diet and physical activity fully account for
quantitative GWG variation in pregnancy is far too simplistic. Weight regulation is a complex process involving
interactions among multiple neurobiological and endocrine pathways, but the central control predominantly
occurs in the mediobasal hypothalamus (MBH), specifically the arcuate nucleus. Recent studies in nonpregnant
humans demonstrate that gliosis (a cellular inflammatory response) in the MBH is associated with obesity.
Studies in rodents exposed to a high-fat diet show that MBH gliosis precedes weight gain and that these glial
inflammatory responses are both necessary and sufficient for weight gain. In humans, increased T2 signal on
T2-weighted brain MRI is a radiologic marker of gliosis. Increased T2 signal in the MBH associates with obesity,
insulin resistance and increased visceral adipose tissue (VAT), independent of body mass index (BMI). VAT, fat
surrounding intra-abdominal solid organs, produces more pro-inflammatory cytokines than subcutaneous fat and
is associated with increased risk for metabolic disease. We, and others, have shown associations between
increased VAT and gestational metabolic disease. Therefore, based on rodent literature and findings in non-
pregnant humans, it seems plausible that MBH gliosis could associate with pathological GWG or affect
preferential deposition of VAT during pregnancy. Foundational data from this R21 proposal will provide the first
information regarding a neural mechanism underlying dysregulated or pathological weight gain in pregnancy.

## Key facts

- **NIH application ID:** 10742432
- **Project number:** 1R21HD109652-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Suchitra Chandrasekaran
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $448,441
- **Award type:** 1
- **Project period:** 2023-08-18 → 2025-08-17

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10742432

## Citation

> US National Institutes of Health, RePORTER application 10742432, The Role of Mediobasal Hypothalamic Gliosis in Gestational Weight Gain and Gestational Visceral Fat Accretion (1R21HD109652-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10742432. Licensed CC0.

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