Night‐Restricted Feeding Promotes Hepatic Lipogenesis in Growing Pigs by Synchronizing Insulin‐Melatonin Circadian Rhythms

Dec 18, 2025FASEB journal : official publication of the Federation of American Societies for Experimental Biology

Eating Only at Night Increases Liver Fat Production in Growing Pigs by Aligning Insulin and Melatonin Daily Cycles

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Nighttime-restricted feeding increased hepatic triglyceride accumulation and altered insulin and melatonin rhythms in a porcine model.

Nighttime eating promoted hepatic lipogenesis compared to daytime-restricted feeding.
The circadian rhythm of circulating insulin was reversed during nighttime feeding, aligning it with melatonin levels.
Synchronous administration of insulin and melatonin significantly increased triglyceride accumulation in porcine liver cells.
Mitochondrial fission was enhanced, while mitochondrial membrane potential and ATP production were reduced during the early circadian phase.
Increased levels of the core clock gene BMAL1 were observed in liver cells during nighttime feeding.

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Mistimed eating disrupts the circadian rhythm of hepatic metabolism, thereby increasing the risk of fatty liver disease. Responding to nutrient status and light cues respectively, insulin and melatonin coordinately regulate hepatic lipid homeostasis and circadian clock oscillation. However, whether non-active phase eating-induced hepatic lipid accumulation involves altered rhythmic interactions between insulin and melatonin remains unclear. This study employed a porcine model to investigate the effects of eating time on hepatic lipid metabolism through a 3-month comparative trial of daytime-restricted feeding (DRF) versus nighttime-restricted feeding (NRF). Compared to DRF, NRF promoted hepatic lipogenesis and reversed the circadian rhythm of circulating insulin, synchronizing it with melatonin. To determine whether the temporal coordination of insulin and melatonin regulates hepatic lipid metabolism, we administered these hormones to immortalized porcine hepatocytes either synchronously (SYN) or alternately (ALT) at 12-h intervals for 72 h. The results showed that SYN increased intracellular triglyceride (TG) accumulation in hepatocytes, enhanced mitochondrial fission, reduced mitochondrial membrane potential and ATP production during circadian time 0-12 phase, while upregulating the core clock gene BMAL1 levels in this stage. Overall, this study demonstrated that nighttime eating in diurnal animals induces an imbalance in BMAL1-mediated hepatic mitochondrial fission and fusion by synchronizing the circadian rhythms of insulin and melatonin, promoting triglyceride accumulation through impaired metabolic efficiency. Our findings establish a mechanistic link between mistimed eating and hepatic steatosis from the perspective of hormone rhythms regulated by food and light, offering new insights for chrononutrition-based interventions in metabolic diseases.