Central nervous system control of triglyceride metabolism

Geerling, J.J. (2013)

Doctoral Thesis

This thesis describes the role of the brain in the regulation of peripheral triglyceride metabolism, in the context of the metabolic syndrome. Based on various pharmacological studies we described the role of two hormones, insulin and glucagon-like peptide-1, in the production and clearance of triglycerides. We showed that insulin stimulates the uptake of (triglyceride-derived) fatty acids and that the brain plays an essential role in this process. Additionally, we showed that the glucagon-like peptide-1 receptor analogue exendin-4 decreases triglyceride production by the liver, albeit that the brain does not seem to be involved in this effect. Furthermore, we unraveled the mechanism underlying the effects of metformin, the first-line drug used to treat Type 2 Diabetes, on triglyceride metabolism. We showed that metformin lowers plasma triglyceride levels by stimulating the uptake and subsequent oxidation of triglycerides by the brown adipose tissue, and herewith provided new therapeutical opportunities for this drug. Finally, we showed that apolipoprotein A5, a stimulator of triglyceride hydrolysis and subsequent clearance from the plasma, plays a role in the central regulation of food intake, and herewith described a novel function for this apolipoprotein.

• Metformin
• White adipose tissue
• Brown adipose tissue
• Liver
• Exendin-4
• Insulin
• NPY
• ApoA5
• Triglycerides
• Sympathetic nervous system

• All authors: Geerling, J.J.
• Supervisor: Rensen, P.C.N.; Romijn, J.A.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden University Medical Center (LUMC), Leiden University
• Date: 2013-10-23
• ISBN (print): 9789462034488
• Sponsorship: Dutch Heart Foundation, Boehringer Ingelheim B.V., Novo Nordisk B.V., Bachem Peptides B.V.