Jacob Smith

@jacobsmithsci.bsky.social

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PI @UniBarcelona @IBUB_UB. https://sites.google.com/view/smithlab-ibub/home?authuser=0 Circadian clocks and inter-organ crosstalk.

This graphical abstract summarizes the role of the liver circadian clock in regulating skeletal muscle metabolism through endocrine signaling. In wild-type (WT) mice, the liver clock is intact (functional), whereas in hepatocyte-specific Bmal1 knockout mice (Bmal1hep−/−) the liver clock is disrupted (core clock rhythms completely absent). RNA-sequencing analysis of skeletal muscle shows that deletion of the liver clock does not alter the core molecular clock machinery in muscle but modifies the rhythmic expression of metabolic genes, particularly those associated with mitochondrial and lipid metabolism.

To investigate whether this regulation occurs through circulating factors, serum collected from WT or Bmal1hep−/− mice during different circadian phases was applied to cultured skeletal muscle myotubes. RNA-sequencing of myotubes revealed that serum from Bmal1hep−/− mice, particularly during the dark phase (ZT16), reduces the expression of oxidative phosphorylation and other mitochondrial genes compared with WT serum. Functional assessment demonstrated that treatment with Bmal1hep−/− serum decreases mitochondrial respiration and ATP production in myotubes.

Together, these findings illustrate that the liver circadian clock communicates with skeletal muscle through blood-borne signals to fine-tune muscle metabolic gene expression and mitochondrial function without directly altering the intrinsic muscle clock. This endocrine liver–muscle signaling axis highlights a mechanism by which peripheral clocks coordinate systemic metabolism across tissues.

word cloud showing research focus of Jacob Smith. Main words are circadian, clock, liver, muscle, metabolic