Abstract 4004: Body Mass is Significantly Associated with Decreased Sterol Resorption and Increased Cholesterol Synthesis: Results of the Population-based MONICA/KORA Survey 1994/95
Serum plant sterol levels are markers for intestinal sterol resorption. Bioactive cholesterol precursors as lanosterol are markers for cholesterol synthesis. Preliminary data from smaller studies show that cholesterol absorption and synthesis can be modulated by body weight in patients with type II diabetes and coronary heart disease. However, there are no data from population-representative surveys available to confirm or to disprove this observation. The association of body weight with the development of metabolic syndrome and disorders of lipid metabolism supports the imperative to elucidate the effects of body weight on sterol resorption and synthesis in the healthy population. Thus, we investigated the association of serum markers for sterol resorption and cholesterol synthesis with age and body weight in available blood samples from 4183 apparently healthy 25 to 74 year old participants (2063 males and 2129 females) of the MONICA (Monitoring of Trends and determinants in cardiovascular disease) survey 1994/95. A high-throughput platform based on LC-MS/MS using atmospheric pressure photoionization was developed and applied. This novel method allows a rapid determination of phytosterols and the cholesterol precursor lanosterol. Male subjects with BMI < 25 (n=553), 25–29,9 (n=1111), >30 kg/m2 (n=399) showed plasma campesterol levels of 6.21 , 5.76, 5.20 mg/l (p<0.001), or plasma lanosterol levels of 0.151, 0.185, 0.210 mg/l (p<0.001), respectively. Comparable associations were observed for female subjects and could be confirmed in each 10 year age stratum (25 - 74y). Our results demonstrate for the first time in a large population-representative sample a significant association between the resorption of sterols, cholesterol synthesis and body weight. The inverse correlation between body weight and sterol resorption could be an early indicator of a metabolic syndrome, because hyperinsulinemia can enhance ATP-Binding Cassette half-transporters (ABCG5/8) activity, which is implicated in control of hepatobiliary cholesterol secretion and intestinal cholesterol absorption. This age-independent inverse effect of BMI has to be taken into account in the evaluation of plasma sterols and their effects on cardiovascular outcomes.