# Testing the Adipose Expandability Hypothesis In Vivo During Overfeeding

> **NIH NIH R01** · LSU PENNINGTON BIOMEDICAL RESEARCH CTR · 2021 · $623,354

## Abstract

PROJECT SUMMARY/ABSTRACT
 Adipose expansion is necessary to accommodate chronic excess caloric intake and characterized by an
increase in adipocyte size (hypertrophy) and number (hyperplasia; adipogenesis). Though obesity is related to
AT lipid handling and storage capacity, the mechanisms underlying the link between obesity and the metabolic
syndrome (MetS) are poorly understood. The AT expandability hypothesis postulates that the capacity for
subcutaneous (subQ) adipose expansion is a significant determinant of metabolic health, as impaired
adipogenesis (limited hyperplasia) may lead to ectopic lipid deposition in non-adipose organs, contributing to the
development of obesity-associated diseases. Some in vitro studies report a higher population of small fat cells
(i.e. hyperplasia) in individuals with MetS and type 2 diabetes. Data from two human overfeeding studies (one
from our group) demonstrate that a smaller adipocyte size resulted in a greater impairment of insulin sensitivity
with weight gain. We are the only group to assess in vivo adipogenesis in subQ AT via the incorporation of
deuterium (2H) into adipose cells of obese women and show that higher adipocyte formation was associated with
facets of impaired metabolic health. Our findings and others are contrary to the AT expandability hypothesis and
provide evidence that higher (not lower) adipogenesis (i.e. hyperplasia) is associated with obesity-related
disorders. Using a randomized controlled trial (RCT), we will examine the effects of a 9-week intervention on
mechanisms of AT expandability. Overweight men and women will be randomized to 30% overfeeding (OF) or
a weight stable Control (CTL) group. The objectives of the proposal are to test in vivo adipogenesis, using a
validated 2H-labeling approach, and other mechanisms of subQ AT expansion in response to weight gain, and
to assess the relationship of adipose expansion with changes in metabolic outcomes. The primary hypothesis is
that higher adipogenesis in response to OF will be accompanied by increased visceral adiposity and ectopic
lipid, reduced insulin sensitivity, and pathological AT remodeling in individuals with impaired subQ AT expansion.
Therefore, despite hyperplasia in weight gainers, a limited storage capacity of adipocytes may facilitate impaired
health outcomes. This is the first RCT to test the validity of the `AT expandability hypothesis'. Findings will provide
new knowledge on the influence of adipose characteristics on the metabolic responses to dynamic changes in
weight in humans.

## Key facts

- **NIH application ID:** 10085635
- **Project number:** 5R01DK121944-02
- **Recipient organization:** LSU PENNINGTON BIOMEDICAL RESEARCH CTR
- **Principal Investigator:** Ursula White
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $623,354
- **Award type:** 5
- **Project period:** 2020-01-15 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10085635

## Citation

> US National Institutes of Health, RePORTER application 10085635, Testing the Adipose Expandability Hypothesis In Vivo During Overfeeding (5R01DK121944-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10085635. Licensed CC0.

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