# High-Protein Diet Prevents Glucocorticoid-Induced Fat Mass Accumulation and Hyperglycemia

**Authors:** Susan J. Burke, Heidi M. Batdorf, Maggie P. Ducote, Thomas M. Martin, Michael D. Karlstad, Robert C. Noland, Sujoy Ghosh, Christopher D. Morrison, J. Jason Collier

PMC · DOI: 10.3390/ijms26094212 · 2025-04-29

## TL;DR

A high-protein diet helps prevent weight gain and high blood sugar in mice treated with glucocorticoids.

## Contribution

The study shows a high-protein diet prevents hyperglycemia and fat accumulation during glucocorticoid therapy in mice.

## Key findings

- A high-protein diet prevented fat mass accumulation in mice on glucocorticoids.
- Mice on a high-protein diet did not develop hyperglycemia, unlike those on a normal-protein diet.
- The diet altered gene expression in adipose tissue and liver but did not improve insulin sensitivity.

## Abstract

Glucocorticoid-induced diabetes is the most common form of drug-induced hyperglycemia. In addition, chronic exposure to glucocorticoids promotes lean mass loss and fat mass accumulation. In this study, we hypothesized that a high-protein diet (60% kcal; HPD) would help to offset sarcopenia during oral administration of corticosterone to C57BL/6J mice. Carbohydrates were reduced in the HPD to ensure it was isocaloric with the normal-protein diet (20% kcal; NPD). We found that the HPD prevented fat mass accumulation but did not protect against reductions in lean mass in both male and female mice. Mice consuming a HPD did not develop hyperglycemia, while mice given the NPD developed hyperglycemia within two weeks. The HPD diet did not improve insulin sensitivity in response to glucocorticoids but did alter gene expression patterns in adipose tissue and liver measured by RNA sequencing. We conclude that a HPD diet may be beneficial to limit rises in blood glucose and adipose tissue accrual during glucocorticoid therapy.

## Linked entities

- **Chemicals:** corticosterone (PubChem CID 5753)
- **Diseases:** diabetes (MONDO:0005015), hyperglycemia (MONDO:0002909)

## Full-text entities

- **Diseases:** sarcopenia (MESH:D055948), Fat Mass (MESH:C536030), diabetes (MESH:D003920), Hyperglycemia (MESH:D006943), lean mass loss (MESH:D013851)
- **Chemicals:** corticosterone (MESH:D003345), blood glucose (MESH:D001786), Carbohydrates (MESH:D002241)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** C57BL/6J — Mus musculus (Mouse), Transformed cell line (CVCL_C0MW)

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12071877/full.md

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Source: https://tomesphere.com/paper/PMC12071877