Reprogramming of rhythmic liver metabolism by intestinal clock

Bmal1-intestine-specific knockout (iKO) mice exhibited a large-scale reprogramming of the rhythmic transcriptome of the liver.

• The liver clock remained resistant to changes in feeding patterns and high-fat diets in the absence of intestinal Bmal1.
• Knockout of Bmal1 shifted the liver's metabolism from fat production to glucose production during the dark phase, resulting in hyperglycaemia and insulin insensitivity.
• Rev-erba iKO mice showed a metabolic shift from glucose production to fat production during the light phase, increasing vulnerability to alcohol-related liver injury.
• Disruption of liver metabolism was linked to changes in the rhythmic patterns of a protein that regulates fat synthesis, which was influenced by gut-derived fatty acids.
• These findings suggest that the intestinal clock plays a crucial role in regulating liver function and metabolism.

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