Universiteit Leiden

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PhD defence

Targeting Inter-Organ Cross-Talk in Cardiometabolic Diseases

  • C. Liu
Tuesday 16 May 2023
Academy Building
Rapenburg 73
2311 GJ Leiden


  • Prof.dr. P.C.N. Rensen
  • Prof.dr. Y. Wang
  • dr. M. Schönke


Cardiometabolic health is tightly controlled by a complex network of organ communication. Dysfunction of these lines of communication is associated with the development of cardiometabolic diseases, indicating inter-organ cross-talk as a therapeutic target. Herein, I explored the therapeutic potential of targeting inter-organ communication in cardiometabolic diseases, including obesity, atherosclerotic cardiovascular disease, and non-alcoholic steatohepatitis, based on which I proposed novel therapies to tackle these diseases. On one hand, strategies can focus on regulating the gut microbiota-centered inter-organ cross-talk. I demonstrated that dietary interventions are efficient to modulate the gut microbiota composition and function, thereby regulating the gut microbial metabolite production. In particular, I showed that dietary supplementation of butyrate, a gut microbial metabolite, and choline, a nutrient enriched in red meat, can beneficially modulate the gut microbiota to alleviate adiposity. On the other hand, therapies can also focus on liver-centered inter-organ cross-talk. We showed that improving hepatocyte mitochondrial function by γ hydroxybutyric acid not only improves liver metabolic function but also reverses obesity and its associated metabolic diseases. Besides, cardiometabolic health can be improved by regulating systemic levels of hepatokines (e.g. FGF21). We showed that FGF21-based pharmacotherapies can regulate the cross-talk between the liver and adipose tissue to improve cardiometabolic diseases, especially fibrotic non-alcoholic steatohepatitis, and atherosclerotic cardiovascular disease. Thus, the findings described in this thesis emphasize the importance of inter-organ cross-talk for cardiometabolic diseases and have improved our knowledge of the mechanisms that underlie the risk in the ever-increasing population of individuals who suffer from cardiometabolic diseases.

PhD dissertations

Approximately one week after the defence, PhD dissertations by Leiden PhD students are available digitally through the Leiden Repository, that offers free access to these PhD dissertations. Please note that in some cases a dissertation may be under embargo temporarily and access to its full-text version will only be granted later.

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