Leiden University Scholarly Publications

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Hoekx, C.A. (2025)

Metabolic hormones and ethnic aspects in obesity

Doctoral Thesis
Obesity is a chronic and increasingly prevalent disease characterized by excess body fat, particularly abdominal fat. It is a major global health concern and a key risk factor for conditions such as type 2 diabetes mellitus (T2DM), cardiovascular disease, and certain types of cancer. Individuals of South Asian descent face a higher risk of developing obesity-related diseases than those of European descent, even at comparable body mass index (BMI) levels. This thesis examined potential underlying mechanisms behind this ethnic disparity.
The findings revealed that South Asians differ in hormonal and inflammatory profiles compared to Europids. For example, South Asians with T2DM exhibited lower concentrations of the anti-inflammatory hormone FGF21. Furthermore, even young, healthy South Asians showed distinct postprandial responses, including differences in blood glucose and hunger- and satiety-related hormones, which may contribute to their elevated T2DM risk.
The thesis also...Show moreObesity is a chronic and increasingly prevalent disease characterized by excess body fat, particularly abdominal fat. It is a major global health concern and a key risk factor for conditions such as type 2 diabetes mellitus (T2DM), cardiovascular disease, and certain types of cancer. Individuals of South Asian descent face a higher risk of developing obesity-related diseases than those of European descent, even at comparable body mass index (BMI) levels. This thesis examined potential underlying mechanisms behind this ethnic disparity.
The findings revealed that South Asians differ in hormonal and inflammatory profiles compared to Europids. For example, South Asians with T2DM exhibited lower concentrations of the anti-inflammatory hormone FGF21. Furthermore, even young, healthy South Asians showed distinct postprandial responses, including differences in blood glucose and hunger- and satiety-related hormones, which may contribute to their elevated T2DM risk.
The thesis also investigated interventions to improve fat metabolism. Cold exposure was found to activate brown adipose tissue (BAT), partially via FGF21, but only evening exposure increased circulating FGF21 levels. Additionally, pharmacological stimulation of BAT using the β2-adrenergic agonist salbutamol significantly enhanced BAT activity, offering a promising therapeutic avenue.
These findings underscore the importance of tailored strategies for populations at elevated metabolic risk, such as South Asians.
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Obesity
South Asian
Brown adipose tissue
Mixed Meal test
Energy metabolism
Cold Exposure
Incretin hormones
Cardiometabolic diseases
Glucose metabolism
Inflammation
All authors
Hoekx, C.A.
Supervisor
Rensen, P.C.N.
Co-supervisor
Boon, M.R.; Martinez-Tellez, B.
Committee
Pijl, H.; Rossum, E.F.C. van; Goossens, G.H.; Born, B.J.H. van den
Qualification
Doctor (dr.)
Awarding Institution
Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Date
2025-06-25
ISBN (print)
9789465223520

Funding

Sponsorship
The research described in this thesis was supported by a grant of the Dutch Research Council NWO (VENI grant 09150161910073) and partially financially supported by Roba Metals B.V., IJsselstein, The Netherlands. Financial support by the Netherlands Association for the Study of Obesity (NASO) for the publication of this thesis is gratefully acknowledged