From measurements of the autocorrelation function and time-averaged intensity of light scattered from aqueous bile salt-lecithin solutions, we deduced the mean hydrodynamic radius (Rh), shape, and polydispersity of bile salt-lecithin mixed micelles as functions of bile salt species, lecithin to bile salt (L/BS) molar ratio, total lipid concentration (0.625-10 g/dL), temperature (20-60 degrees C), and NaCl concentration (0.15-0.6 M). Our data suggest that at low L/BS ratios (0 to approximately 0.6) simple bile salt micelles coexist in varying proportions with minimum-sized mixed micelles (Rh, 18-35 A). These solutions are highly polydisperse and display features dependent upon the particular bile salt species. At high L/BS ratios (greater than 0.6), only mixed micelles are present, and their sizes increase markedly (Rh, 20 leads to 300 A) with increases in L/BS ratio and appear to diverge as the lecithin-bile salt phase limit is approached. The shape of the mixed micelles as deduced from light-scattering measurements and confirmed by transmission electron microscopy is disklike. The radii of the disks, however, are not compatible with Small's model of mixed micellar structure [Small, D.M. (1967a) Gastroenterology 52, 607-a1 but are consistent with a new model proposed here in which bile salts and lecithin interact to form a mixed bilayer disk which is surrounded on its perimeter by bile salts. The inclusion of bile salts in a fixed stoichiometry within the interior of the bilayers is shown to provide a quantitative explanation for the divergence of the mixed micellar sizes, their temperature dependence, and the origin of the lecithin-bile salt phase limit. The influence of total lipid concentration on both mixed micellar size and the lecithin-bile salt phase limit is explained by the "mixed disk" model by taking account of the equilibrium between mixed micelles and bile salt monomers in the intermicellar solution. By use of this concept, deductions of the intermicellar bile salt concentration in taurocholate-lecithin solutions are made and are shown to vary as a function of mixed micellar size and temperature. The range of values obtained, 3-6 mM, is comparable in magnitude to the critical micellar concentration of the pure bile salt.

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Publication costs assisted by the National Science Foundation and National Institutes of Health Measurements of the autocorrelation function and average intensity of light quasielastically scattered from aqueous solutions of sodium dodecyl sulfate (SDS) in the presence of added NaCl were carried out over a wide region of the micellar phase and in the supercooled state below the critical micellar temperature (cmt). The mean size, shape, aggregation number, and polydispersity of SDS micelles have been deduced as a function of température (10-85 °C) and NaCl concentration (0.15-0.6 M) for detergent concentrations (1.7 X IQ-2, 3.5 X 10~2, and 6.9 X 10~2 M) which appreciably exceed the critical micellar concentration (cmc). At these SDS concentrations the size and shape of the micelles show a marked dependence on the temperature and NaCl concentration. A minimum micellar size corresponding to a sphere with a hydrated radius of about 25 Á is asymptotically approached at high temperature in all NaCl concentrations. In NaCl concentrations greater than 0.3 M significant micellar growth occurs as the temperature is.lowered, and the enlarged SDS micelle can be approximated by a prolate ellipsoid with a semiminor axis of 25 Á and a semimajor axis that approaches 675 A in 0.6 M NaCl. The mean aggregation numbers of these rodlike micelles were found to vary approximately with the square root of thé SDS concentration, and the width of the distribution of aggregation numbers was estimated at ±70% of the mean value. In supercooled solutions, micellar size and shape have the same dependence on detergent concentration, NaCl concentration, and temperature as occurs above the crht. It is demonstrated that the cmt, its dependence on NaCl concentration, and the metastability of supercooled micellar solutions can be qualitatively understood by an extension of the Murray-Hartley theory of detergent solubility which accounts for the cmt phenomenon on the basis of the coupling between the monomer-hydrated solid equilibrium and the monomer-micelle equilibrium.

Insulin resistance plays a central role in the development of the metabolic syndrome, but how it relates to cardiovascular disease remains controversial. Liver insulin receptor knockout (LIRKO) mice have pure hepatic insulin resistance. On a standard chow diet, LIRKO mice have a proatherogenic lipoprotein profile with reduced high-density lipoprotein (HDL) cholesterol and very low-density lipoprotein (VLDL) particles that are markedly enriched in cholesterol. This is due to increased secretion and decreased clearance of apolipoprotein B-containing lipoproteins, coupled with decreased triglyceride secretion secondary to increased expression of Pgc-1 beta (Ppargc-1b), which promotes VLDL secretion, but decreased expression of Srebp-1c (Srebf1), Srebp-2 (Srebf2), and their targets, the lipogenic enzymes and the LDL receptor. Within 12 weeks on an atherogenic diet, LIRKO mice show marked hypercholesterolemia, and 100% of LIRKO mice, but 0% of controls, develop severe atherosclerosis. Thus, insulin resistance at the level of the liver is sufficient to produce the dyslipidemia and increased risk of atherosclerosis associated with the metabolic syndrome.