Targeting inter-organ cross-talk in cardiometabolic diseases

Liu, C.

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. We demonstrated that dietary interventions are efficient to modulate the gut microbiota composition and function, thereby regulating the gut microbial metabolite production⁠. In particularly, we showed that dietary supplementation of butyrate, a gut microbial metabolite, and choline, a nutrient enriched in red meat, can beneficially modulate the gut...Show moreCardiometabolic 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. We demonstrated that dietary interventions are efficient to modulate the gut microbiota composition and function, thereby regulating the gut microbial metabolite production⁠. In particularly, we 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 on the mechanisms that underlie the risk in the ever-increasing population of individuals who suffer from cardiometabolic diseases⁠.
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Targeting inter-organ cross-talk in cardiometabolic diseases