Ectopic fat depositions in obesity and diabetes : nutritional, exercise and pharmacological interventions

Jonker, J.T. (2012)

Doctoral Thesis

The studies described in this thesis explored the effects of nutritional, exercise and pharmacological interventions on ectopic triglyceride accumulation in obese patients and/or patients with type 1 or type 2 diabetes mellitus (T2DM). Ectopic fat is defined as triglyceride (TG) storage in tissues, other than adipose tissue, such as the liver, heart and skeletal muscle. The focus of this thesis is on ectopic fat accumulation in two important organs: the liver and the heart. Studies in current thesis indeed have shown that lifestyle and pharmacological interventions can change ectopic triglyceride accumulation in (advanced) T2DM and is associated with changes in function. However, the notion emerges that the different fat compartments have differential regulation in relation to exercise, nutrition and pharmacological interventions. This points to different regulatory mechanisms involved in the accumulation and/or lipolysis of these fat compartments. Alternatively, it is possible that similar mechanisms are involved but with different dose-response relationships. These cannot be derived from the studies described in the current thesis because the aims of these studies were not focussed at these mechanisms underlying the dynamics of the individual fat depots. As patients with obesity and T2DM may have different ectopic fat distribution, this may also affect their (cardiac) risk profile. Manchann et al. already studied the effect of lifestyle intervention versus antidiabetic medication in patients with different fat distribution and found that this could predict intervention failure. More studies in these dynamics will hopefully lead to understanding from which treatments specific patient groups will benefit most.

• Very low calorie diet
• Pericardial fat
• Magnetic resonance spectroscopy
• Magnetic resonance imaging
• Hepatic steatosis
• Exercise
• Ectopic fat
• Diastolic cardiac function

• All authors: Jonker, J.T.
• Supervisor: Smit, J.W.A.; Romijn, J.A.; Roos, A. de
• Co-supervisor: Lamb, H.J.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden University Medical Center (LUMC), Leiden University
• Date: 2012-10-10
• ISBN (print): 9789461692733