Time-restricted feeding alleviates heat stress-induced liver ferroptosis in piglets via nuclear receptor NR1D1-mediated transcription modulation

May 13, 2026The Journal of nutritional biochemistry

Time-restricted feeding may reduce heat stress liver cell death in piglets by changing gene activity through the NR1D1 receptor

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Chronic heat exposure significantly decreased hepatic glutathione levels and increased lipid peroxidation.

Chronic heat exposure led to reduced antioxidant enzyme activities and impaired mitochondrial structure.
Transcriptomic analysis showed increased expression of ferroptosis-related genes such as TFRC, ACSL4, and HMOX1.
Decreased expression of protective genes like GPX4 and SLC7A11 was also observed under heat stress.
Time-restricted feeding partially restored antioxidant levels and improved mitochondrial integrity.
TRF attenuated transcriptional alterations associated with ferroptosis and modulated expression patterns of redox-related genes.

AI simplified

BACKGROUND: Heat stress (HS) disturbs hepatic metabolic homeostasis and redox balance, compromising antioxidant capacity and mitochondrial function. Ferroptosis, a lipid peroxidation-associated form of regulated cell death, has been implicated in redox-sensitive metabolic disorders. Whether nutritional timing influences HS-associated ferroptotic responses in the liver remains unclear. This study examined the effects of time-restricted feeding (TRF) on hepatic redox regulation and ferroptosis-related molecular pathways under chronic heat exposure.

METHODS: Piglets were exposed to cyclic heat challenge (35°C, 4 h/day) for 65 days with or without TRF intervention. Hepatic oxidative status, mitochondrial function, and ferroptosis-associated gene and protein expression were evaluated using biochemical assays, transcriptomic analysis, RT-qPCR, western blotting, and chromatin immunoprecipitation.

RESULTS: Chronic heat exposure was associated with decreased hepatic glutathione levels, increased lipid peroxidation, reduced antioxidant enzyme activities, impaired mitochondrial ultrastructure, and lower ATP production (P < 0.05). Transcriptomic profiling revealed coordinated changes in ferroptosis-related genes, including increased TFRC, ACSL4, and HMOX1 expression and decreased GPX4, SLC7A11, and NFE2L2 expression (P < 0.05). Heat exposure was accompanied by elevated NR1D1 expression and altered promoter occupancy at redox-related genes. TRF partially restored antioxidant status, improved mitochondrial integrity, attenuated ferroptosis-associated transcriptional alterations, and modulated NR1D1 expression patterns (P < 0.05).

CONCLUSIONS: These findings suggest that chronic HS is associated with hepatic redox disruption and ferroptosis-related molecular changes. TRF may mitigate these metabolic disturbances through modulation of redox-sensitive transcriptional regulation.

Full Text

Full text is available at the source.

View full text (XML) ↗View full text ↗

Time-restricted feeding alleviates heat stress-induced liver ferroptosis in piglets via nuclear receptor NR1D1-mediated transcription modulation

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief