# The effects of time-restricted feeding on early phases of carcinogenesis in rat liver and colon

**Authors:** Nadia Malakmahmoudi, Roberta Pisu, Andrea Barbarossa, Francesca Pisu, Giuseppe S. Porcu, Ezio Laconi, Andrea Perra, Sergio Uzzau, Fabio Marongiu

PMC · DOI: 10.3389/fnut.2026.1650934 · Frontiers in Nutrition · 2026-01-23

## TL;DR

This study found that time-restricted feeding does not reduce early cancer development in rat liver and colon, even when combined with high-fat diets.

## Contribution

The study provides new empirical evidence on the limited effectiveness of time-restricted feeding in mitigating early carcinogenesis in rats.

## Key findings

- TRF did not reduce preneoplastic lesions in the liver or colon of rats.
- TRF failed to improve hepatic steatosis or lipid profiles in high-fat diet-fed rats.

## Abstract

High-fat diets are established contributors to carcinogenesis through mechanisms involving altered lipid metabolism, metabolic stress, and chronic inflammation. Time-restricted feeding (TRF) has emerged as a promising non-pharmacological strategy to improve metabolic health and potentially mitigate cancer risk by optimizing glycemic control, lipid profile, and inflammatory triggers. Despite these potential benefits, the direct impact of TRF on early-stage carcinogenesis, particularly in the context of obesogenic dietary conditions, remains inadequately explored. This study aimed to investigate the effects of TRF on the development of preneoplastic lesions in the liver and colon in male and female rats exposed to high-fat (HFD) and low-fat (LFD) diets.

Carcinogenesis was initiated using diethyl nitrosamine (DENA) for the liver and azoxymethane (AOM) for the colon. Rats were assigned to ad libitum feeding (AdL) or TRF (8-h feeding window) following carcinogen exposure and were euthanized at 6 or 9 months for assessment. Pre-neoplastic lesions in the liver were evaluated by glutathione S-transferase placental form (GSTP)-positive staining, while aberrant crypt foci (ACF) were analyzed in the colon. Additionally, hepatic steatosis and metabolic parameters were assessed to determine the impact of TRF.

No differences were observed in the incidence, size, or distribution of GSTP-positive lesions in the liver or ACF in the colon between TRF and AdL groups. TRF also failed to reduce hepatic steatosis or improve serum lipid profiles in animals fed an HFD.

Our findings indicate that TRF does not significantly alter the development of early preneoplastic lesions in the liver or colon, regardless of dietary fat content, and further suggest that this dietary regimen is insufficient alone to counteract metabolic dysfunctions induced by highly obesogenic diets in rats.

## Linked entities

- **Chemicals:** diethyl nitrosamine (PubChem CID 5921), azoxymethane (PubChem CID 33184)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Gstp1 (glutathione S-transferase pi 1) [NCBI Gene 24426] {aka GST-P, Gst3, Gstp, Gstp2}
- **Diseases:** metabolic dysfunctions (MESH:D008659), chronic inflammation (MESH:D007249), Carcinogenesis (MESH:D063646), hepatic steatosis (MESH:D005234), cancer (MESH:D009369), preneoplastic lesions (MESH:D011230)
- **Chemicals:** DENA (MESH:D004052), fat (MESH:D005223), AOM (MESH:D001397), lipid (MESH:D008055)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12875941/full.md

## References

53 references — full list in the complete paper: https://tomesphere.com/paper/PMC12875941/full.md

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Source: https://tomesphere.com/paper/PMC12875941