Metabolic consequences of adipose tissue dysfunction

This thesis focuses on the consequences of adipose tissue dysfunction (ATD), which is defined as the imbalance of pro- and anti-inflammatory adipocytokines produced by adipose tissue. ATD leads to the development of the metabolic syndrome, cardiovascular diseases and diabetes. Although the quantity of adipose is an important factor in the pathogenesis of ATD, the existence of metabolically healthy obese and normal weight metabolically unhealthy individuals proves that quality of adipose tissue is important. Therefore, diagnosis of ATD in both obese and normal weight individuals might lead to better risk stratification and contribute to better prevention of cardiovascular diseases and diabetes. Diagnosing ATD on an individual level is currently best done by determining metabolic syndrome criteria. Other options for diagnosing ATD are explored in this thesis, such as examining free fatty acid composition of adipose tissue in lean and obese individuals, measured with Magnetic Resonance Spectroscopy (MRS). After ensuring adequate reproducibility of this relatively new technique in adipose tissue, it was shown that individuals with metabolic syndrome differ from those without metabolic syndrome regarding their free fatty acid composition in visceral adipose tissue. Moreover, the handling of an oral fat challenge by the visceral adipose tissue is different between individuals with and without the metabolic syndrome. Another option for diagnosing ATD explored in this thesis is measuring adipokine levels. Higher adipokine levels are associated with (components of) the metabolic syndrome and blood pressure. Combining adipokines into an adipokine profile (since the interplay between different adipokines and not single adipokine levels are likely to determine ATD) was also related to the metabolic syndrome. The second part of the thesis covers the treatment of obesity related hypertension. Patients with obesity-related hypertension are best treated with RAAS-blockers, possibly due to the ability of excess adipose tissue to produce angiotensin II and aldosterone. None of the possible three pathophysiological mechanisms (RAAS activation, sympathetic activity and sodium retention behind obesity-related hypertension could be pointed as the most important one. Diagnosing ATD rather than identifying those with overweight or obesity should become the focus of prevention of cardiovascular disease and diabetes. The diagnosis of ATD could trigger more intensified follow-up and early treatment of hypertension and dyslipidemia. For those being overweight or obese with ATD, there is more urgency of weight reduction than in those without ATD, possibly leading to risk reduction.