Miettinen T A, Gylling H
Department of Medicine, Division of Internal Medicine, University of Helsinki, P.O. Box 340, FIN-00029 HYKS, Helsinki, Finland.
Atherosclerosis. 2000 Nov;153(1):241-8. doi: 10.1016/s0021-9150(00)00404-4.
Role of enterohepatic cholesterol metabolism in obesity-induced increase of cholesterol synthesis was studied in healthy lean (BMI <24) and overweight (BMI >31) subjects by measuring serum lipids (including plant sterols, cholestanol and cholesterol precursors), cholesterol absorption % (double-label method), sterol balance and biliary lipids. New aspects of sterol metabolism in obesity were as follows: low efficiency of cholesterol absorption, reduced ratios to cholesterol of serum and biliary plant sterols and cholestanol (5alpha-derivative of cholesterol), and a marked increase of serum and biliary cholesterol precursor sterols. Percent of cholesterol absorption was positively related to serum cholestanol and plant sterols, and negatively to cholesterol synthesis, measured by the sterol balance technique or cholesterol precursor sterols in serum or bile. Total and endogenous cholesterol fluxes into the intestine were increased, but owing to low absorption percent, mass of cholesterol absorption was within control limits in the obese subjects. Thus, per gram of their large liver tissue the entry of intestinal cholesterol may even be subnormal. Percent of cholesterol absorption was insignificantly negatively (r=-0.256) related to intestinal cholesterol pool, but significantly to biliary concentrations of cholesterol (r=-0.581), bile acids (r=-0.513) and phospholipids (r=-0.469). Thus, dilution of labeled dietary cholesterol by expanded intestinal cholesterol pool could have contributed to subnormal efficiency of cholesterol absorption, or transfer of labeled dietary cholesterol from intestinal oil phase to micellar phase may be competitively inhibited by expanded biliary secretion, resulting in reduced absorption of dietary cholesterol. These mechanisms could have contributed to changes in metabolism of non-cholesterol sterols, especially of cholestanol and plant sterols.
通过测量血清脂质（包括植物甾醇、胆甾烷醇和胆固醇前体）、胆固醇吸收百分比（双标记法）、甾醇平衡和胆汁脂质，研究了肠肝循环胆固醇代谢在肥胖诱导的胆固醇合成增加中的作用。肥胖中甾醇代谢的新情况如下：胆固醇吸收效率低，血清和胆汁中植物甾醇及胆甾烷醇（胆固醇的5α-衍生物）与胆固醇的比率降低，血清和胆汁中胆固醇前体甾醇显著增加。胆固醇吸收百分比与血清胆甾烷醇和植物甾醇呈正相关，与通过甾醇平衡技术或血清或胆汁中的胆固醇前体甾醇测量的胆固醇合成呈负相关。进入肠道的总胆固醇通量和内源性胆固醇通量增加，但由于吸收百分比低，肥胖受试者的胆固醇吸收量在正常范围内。因此，每克他们较大的肝脏组织中肠道胆固醇的进入量甚至可能低于正常水平。胆固醇吸收百分比与肠道胆固醇池呈不显著的负相关（r = -0.256），但与胆汁中胆固醇（r = -0.581）、胆汁酸（r = -0.513）和磷脂（r = -0.469）的浓度显著相关。因此，扩大的肠道胆固醇池对标记膳食胆固醇的稀释可能导致胆固醇吸收效率低于正常水平，或者标记膳食胆固醇从肠道油相转移到胶束相可能受到扩大的胆汁分泌的竞争性抑制，导致膳食胆固醇吸收减少。这些机制可能导致了非胆固醇甾醇代谢的变化，尤其是胆甾烷醇和植物甾醇的代谢变化。
