Proteins of white lupin seed, a naturally isoflavone-poor legume, reduce cholesterolemia in rats and increase LDL receptor activity in HepG2 cells

White lupin (Lupinus albus, L.), a widely cultivated crop that has been consumed for many years in Western Europe, may provide a useful alternative for individuals wishing to substitute animal with plant proteins for cardiovascular disease prevention. Lupin seeds have a very low content of isoflavones, and lupin protein isolates are essentially isoflavone free. In rats fed a casein-based cholesterol + cholic acid diet, a relatively low daily intake (50 mg/d by gavage for 2 wk) of total lupin protein extract reduced plasma total and VLDL + LDL cholesterol concentrations by 21 and 30%, respectively (both P<0.001). In an attempt to elucidate the lipid-lowering mechanism, LDL receptor activity was evaluated in a human hepatoma cell line (HepG2). In this model, the lupin total protein extract was essentially inactive, whereas one purified minor protein component, conglutin gamma, had a remarkable upregulatory effect, with maximal increases of 53 and 21% (both P<0.05) for LDL uptake and degradation, respectively. This initial study indicates that lupin, although isoflavone free, has hypocholesterolemic activity similar to that of other leguminous proteins in an established animal model. Further, the cholesterol reduction appears to be associated with stimulation of LDL receptors by a well-defined protein component of the lupin seeds as demonstrated by in vitro studies

High density lipoprotein-3 heterogeneity in subjects with the apo-AIMilano variant

The structure of high density lipoproteins (HDL) isolated from subjects with the AIMilano (AIM) apoprotein variant was studied by the use of the cross-linking reagent dimethylsuberimidate. The HDL2 subfraction is markedly reduced, as compared to control subjects; the HDL3 subfraction, on the other hand, shows a marked heterogeneity, being characterized by at least three particle subpopulations, identified as HDL3-I, HDL3-II, and HDL3-III. The HDL3 fraction purified from the AI Milano subjects eluted as a symmetrical peak from a 6% agarose column, corresponding to a unimodal particle size distribution. The content of the different HDL3 particles, detected by cross-linking, varied widely along the elution profile, the tail of the peak being enriched in anomalous particles of very small size (HDL3-III). Apoprotein compositional studies indicated that these small HDL3-III may be enriched in the AIM monomer, the larger particles containing more AIM-AII complexes and AIM dimers. All the anomalous HDL3 particles are triglyceride enriched, with a decreased cholesterol ester content. They may be an intermediate product in the cholesterol transfer chain between HDL and very low density lipoproteins, or be generated during interconversion of HDL. These particles may have a functional role in tissue cholesterol homeostasis; their unusual compositional changes may help explain the protection of the studied subjects from tissue cholesterol deposition, in spite of the marked decrease of the total HDL fraction

Peptides from soybean \u3b2-conglycinin modulate lipid homeostasis, oxidation and inflammatory state in in vitro systems

Lipid homeostasis, oxidation and inflammatory state play an important role in the development of several diseases such as atherosclerosis and cancer. The object was to evaluate the effects of five peptides (A=SEEEEEDQ, B=QKEEEKHEWQ, C=RKQEEDEDEEQQRE, D=EITPEKNPQLR, E=KNPQLR) from soybean \u3b2-conglycinin on lipid homeostasis, NO production, iNOS and COX-2 expression, respectively in HepG2 cells, adipocyte (3T3-L1) and macrophage (RAW 264.7) cell lines. Lipid homeostasis markers: peptides C and E, both at 1 \u3bcM, showed an increased expression (mRNAs) of LDL-R (+2.3 and +1.9 fold, respectively), SREBP2 (+1.8 and +3.3 fold, respectively), and a decrease in HMGCoA reductase (-0.71 and -0.31%, respectively). Peptides A, B and D were ineffective. Inflammatory mediators: peptides A, B, and E, tested at 25 \u3bcM, reduced the expression of iNOS (-71, -75 and -44, respectively) and COX-2 (-54, -34 and -79, respectively); peptides C, D showed lower inhibitory capacity. These in vitro data suggest the potential use of soy peptides as nutraceuticals in lipid lowering therapy and in the improvement of the inflammatory state