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ResearchIn-Press PreviewEndocrinologyMetabolism Open Access | 10.1172/jci.insight.207013

Food insecurity in young rats induces metabolic remodeling in a sex- and diet-dependent manner

Jie An,1 Jessica Cannavino,1 Ashley Williams,1 Akshay Bareja,1 Wenxin Tong,1 Olga Ilkayeva,1 Michael Muehlbauer,1 Danhong Lu,1 Robert A. Hollander,1 Sarah Armstrong,2 Rana K. Gupta,1 and Christopher B. Newgard1

1Duke Molecular Physiology Institute and Sarah W. Stedman Nutrition and Meta, Duke University Medical Center, Durham, United States of America

2Department of Pediatrics and Duke Center for Childhood Obesity Research, Duke University Medical Center, Durham, United States of America

Find articles by An, J. in: PubMed | Google Scholar

1Duke Molecular Physiology Institute and Sarah W. Stedman Nutrition and Meta, Duke University Medical Center, Durham, United States of America

2Department of Pediatrics and Duke Center for Childhood Obesity Research, Duke University Medical Center, Durham, United States of America

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1Duke Molecular Physiology Institute and Sarah W. Stedman Nutrition and Meta, Duke University Medical Center, Durham, United States of America

2Department of Pediatrics and Duke Center for Childhood Obesity Research, Duke University Medical Center, Durham, United States of America

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1Duke Molecular Physiology Institute and Sarah W. Stedman Nutrition and Meta, Duke University Medical Center, Durham, United States of America

2Department of Pediatrics and Duke Center for Childhood Obesity Research, Duke University Medical Center, Durham, United States of America

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1Duke Molecular Physiology Institute and Sarah W. Stedman Nutrition and Meta, Duke University Medical Center, Durham, United States of America

2Department of Pediatrics and Duke Center for Childhood Obesity Research, Duke University Medical Center, Durham, United States of America

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1Duke Molecular Physiology Institute and Sarah W. Stedman Nutrition and Meta, Duke University Medical Center, Durham, United States of America

2Department of Pediatrics and Duke Center for Childhood Obesity Research, Duke University Medical Center, Durham, United States of America

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1Duke Molecular Physiology Institute and Sarah W. Stedman Nutrition and Meta, Duke University Medical Center, Durham, United States of America

2Department of Pediatrics and Duke Center for Childhood Obesity Research, Duke University Medical Center, Durham, United States of America

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1Duke Molecular Physiology Institute and Sarah W. Stedman Nutrition and Meta, Duke University Medical Center, Durham, United States of America

2Department of Pediatrics and Duke Center for Childhood Obesity Research, Duke University Medical Center, Durham, United States of America

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1Duke Molecular Physiology Institute and Sarah W. Stedman Nutrition and Meta, Duke University Medical Center, Durham, United States of America

2Department of Pediatrics and Duke Center for Childhood Obesity Research, Duke University Medical Center, Durham, United States of America

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1Duke Molecular Physiology Institute and Sarah W. Stedman Nutrition and Meta, Duke University Medical Center, Durham, United States of America

2Department of Pediatrics and Duke Center for Childhood Obesity Research, Duke University Medical Center, Durham, United States of America

Find articles by Armstrong, S. in: PubMed | Google Scholar

1Duke Molecular Physiology Institute and Sarah W. Stedman Nutrition and Meta, Duke University Medical Center, Durham, United States of America

2Department of Pediatrics and Duke Center for Childhood Obesity Research, Duke University Medical Center, Durham, United States of America

Find articles by Gupta, R. in: PubMed | Google Scholar

1Duke Molecular Physiology Institute and Sarah W. Stedman Nutrition and Meta, Duke University Medical Center, Durham, United States of America

2Department of Pediatrics and Duke Center for Childhood Obesity Research, Duke University Medical Center, Durham, United States of America

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Published October 20, 2026 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.207013.
Copyright © 2026, An et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published October 20, 2026 - Version history
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Abstract

Exposure of humans to food insecurity (FI), involving sporadic access and low nutritional quality, is associated with later life development of metabolic disease phenotypes, but mechanisms are poorly understood. We exposed very young rats to a 20-day FI intervention or ad-lib (AL) feeding, using either standard chow (SC) or high fat/high sucrose (HF/HS) diets, followed by continued AL feeding on the respective diets for 10-13 weeks. We found that male, but not female rats subjected to FI on the HF/HS diet had increased body fat percentage, ratio of adipose to body weight, and fat cell size compared to AL rats, coupled with metabolomic and transcriptomic profiles consistent with reduced fatty acid oxidation in the liver and maladaptive remodeling of adipose tissue. These changes were specific to HF/HS feeding and did not occur with SC diet. Our study defines sex- and diet-specific metabolic remodeling responses to FI that may contribute to future disease phenotypes.

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Supplemental material

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  • Version 1 (October 20, 2026): In-Press Preview

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