Sequential feeding alters hepatic circadian rhythm gene expression and lipid levels in septic mice

Mar 18, 2026JPEN. Journal of parenteral and enteral nutrition

Changing meal times affects daily liver gene activity and fat levels in mice with sepsis

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Abstract

Serum triglyceride and cholesterol levels were significantly lower at 20:00 than at 08:00 in the sequential feeding group.

Sequential feeding may lead to improved lipid metabolism in septic mice compared to continuous feeding.
Extensive liver fat accumulation (hepatocellular steatosis) was observed in the continuous feeding group.
A total of 461 differentially expressed genes were identified between the sequential and continuous feeding groups.
The most enriched pathway among the differentially expressed genes was circadian rhythm.
Fourteen circadian-related genes and transcriptional regulators showed differential expression in the sequential group, compared to four in the continuous group.

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BACKGROUND: The purpose of this study was to investigate the effects and mechanisms of sequential feeding on lipid metabolism in a murine sepsis model.

METHODS: Septic mice were randomly assigned to a continuous or sequential feeding group. In the continuous group, mice were fed ad libitum day and night via using an automatic feeder. In the sequential group, mice received continuous feeding for the first 5 days, followed by physiological feeding starting on Day 6. Physiological feeding was limited to 20:00-08:00 to match the nocturnal feeding pattern of mice. On Day 14, blood samples were collected at 08:00 and 20:00 to measure serum cholesterol and triglycerides. Liver tissues were collected at 20:00 for transcriptomic analysis and hematoxylin and eosin (H&E) staining, and at both time points for circadian rhythm gene analysis using polymerase chain reaction (PCR) array.

RESULTS: In the sequential group, serum triglyceride and cholesterol levels were significantly lower at 20:00 than at 08:00; no such differences were observed in the continuous group. H&E staining revealed extensive hepatocellular steatosis in the continuous group. Four hundred and sixty one differentially expressed genes were identified between the two groups, with circadian rhythm as the most enriched pathway. PCR array revealed 14 differentially expressed circadian-related genes and transcriptional regulators between 08:00 and 20:00 in the sequential group, compared with only four in the continuous group.

CONCLUSION: Sequential feeding modulates serum cholesterol and triglyceride levels in septic mice and preserves differential expression of some hepatic circadian rhythm-related genes at 08:00 and 20:00. However, continuous feeding attenuates the differential expression of these genes and is associated with severe hepatocellular steatosis.

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Sequential feeding alters hepatic circadian rhythm gene expression and lipid levels in septic mice

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