Interventions targeting hepatic and cardiovascular complications of metabolic syndrome

Inia, J.A. (2026)

Doctoral Thesis

Metabolic syndrome is a major global health challenge and comprises a cluster of metabolic abnormalities. These abnormalities are closely linked to steatotic liver disease and cardiovascular complications, which are central to this thesis. Using preclinical models that closely mimic human lipid metabolism, existing and novel interventions targeting steatotic liver disease and atherosclerosis were evaluated.

The results show that repeated weight cycling is not inherently detrimental and can attenuate liver inflammation compared with continuous exposure to an unhealthy diet. In addition, an early gene expression based approach was developed to support the assessment of antifibrotic drug efficacy. Moreover, several metabolic therapies, including GLP‑1 receptor agonists, FGF21 based interventions and lipid lowering agents, demonstrated beneficial effects beyond their primary indications.

Together, these findings highlight the importance of integrated treatment strategies that target multiple organs and pathways and contribute to the development of more effective therapies for patients with metabolic syndrome.

• Metabolic syndrome
• MASLD
• MASH
• Atherosclerosis
• Lipoprotein metabolism
• GLP1
• Translational mouse models
• FGF21
• CETP
• Cholesterol

• All authors: Inia, J.A.
• Supervisor: Jukema, J.W.
• Co-supervisor: Hoek, A.M. van den; Stokman, G.
• Committee: Rensen, P.C.N.; Willems van Dijk, J.A.P.; Bot, I.; Jager, S. de; Princen, H.M.G.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2026-04-23
• ISBN (print): 9789493539112
• DOI: doi:10.60602/1887-4302628
• Sponsorship: NewAmsterdam Pharma; TNO Daan Traas fonds; Stichting Proefdierkundige Informatie