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... 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. Show less
Artificial photosynthesis (AP) is one of the scientific challenges that could help us achieving a global “carbon neutral” society. Photocatalytic water splitting is considered as the first... Show moreArtificial photosynthesis (AP) is one of the scientific challenges that could help us achieving a global “carbon neutral” society. Photocatalytic water splitting is considered as the first challenge of AP, which contains two half reactions: water oxidation and hydrogen evolution. It is widely accepted that a photocatalytic system needs a minimum of three components: a photosensitizer (PS), a catalyst (Cat) and a sacrificial electron donor or acceptor (SE). In such a photocatalytic system, at least three electron-transfer steps can be identified: one between the SE and the excited PS (PS*), one between the photo-reduced or photo-oxidized PS and the Cat, and one between the Cat and its substrate. This thesis on the one hand focused on developing improved molecular components for the two half reactions of water splitting in purely homogeneous systems. On the other hand optimized photocatalytic systems with balances between the driving force of electron transfer from the SE to the PS*, and that of electron transfer between the catalyst and the oxidized or reduced photosensitizer (PS+ or PS–). Show less