Molecular mechanism for changes in proteoglycan binding on compositional changes of the core and the surface of low-density lipoprotein-containing human apolipoprotein B100

OBJECTIVE: The aim of this study was to investigate the molecular mechanism for changes in proteoglycan binding and LDL receptor affinity on two compositional changes in LDL that have been associated with atherosclerosis: cholesterol enrichment of the core and modification by secretory group IIA phospholipase A2 (sPLA2) of the surface. METHODS AND RESULTS: Transgenic mice expressing recombinant apolipoprotein (apo) B and sPLA2 were generated. Recombinant LDL were isolated and tested for their proteoglycan and LDL receptor-binding activity. The results show site A (residues 3148-3158) in apoB100 becomes functional in sPLA2-modified LDL and that site A acts cooperatively with site B (residues 3359-3369), the primary proteoglycan-binding site in native LDL, in the binding of sPLA2-modified LDL to proteoglycans. Our results also show that cholesterol enrichment of LDL is associated with increased affinity for proteoglycans and for the LDL receptor. This mechanism is likely mediated by a conformational change of site B and is independent of site A in apoB100. CONCLUSIONS: Site A in apoB100 becomes functional in sPLA2-modified LDL and acts cooperatively with site B resulting in increased proteoglycan-binding activity. The increased binding for proteoglycans of cholesterol-enriched LDL is solely dependent on site B

Serum triglyceride and cholesterol concentrations and lipoprotein profiles in dogs with naturally occurring pancreatitis and healthy control dogs

Background: Previous studies have reported an association between hyperlipidemia and pancreatitis in dogs, but details of this association remain poorly defined. Hypothesis/Objectives: To compare serum triglyceride and cholesterol concentrations and lipoprotein profiles between dogs with naturally occurring pancreatitis and healthy dogs. Animals: Seventeen dogs with a clinical diagnosis of pancreatitis (Group 1) and 53 healthy control dogs (Group 2). Methods: Prospective case-control study. Results: In Group 1, 3/17 dogs (18%) had hypertriglyceridemia whereas in Group 2, 4/53 dogs (7.5%) had hypertriglyceridemia (odds ratio [OR], 2.63; 95% confidence interval [CI], 0.52-13.14; P =.35). A significant difference was found in serum triglyceride concentrations between Group 1 (median, 67 mg/dL) and Group 2 (median, 54 mg/dL; P =.002). In Group 1, 4/17 dogs (24%) had hypercholesterolemia, whereas 1/53 (1.9%) dogs in Group 2 had hypercholesterolemia (OR, 16; 95% CI, 1.64-155.5; P =.01). No significant difference was found in serum cholesterol concentrations between Group 1 (median, 209 mg/dL) and Group 2 (median, 227 mg/dL; P =.56). Lipoprotein profiles were significantly different between Group 1 and Group 2 dogs (Eigenvalues, 0.6719; R2 = 1.0; P =.001). Conclusions and Clinical Importance: Most dogs with pancreatitis (>70%) had serum triglyceride and cholesterol concentrations within reference intervals. In the small percentage of dogs that had hypertriglyceridemia, hypercholesterolemia, or both, increases were mild. Important differences were identified in lipoprotein profiles between dogs with pancreatitis and healthy control dogs. Dogs with pancreatitis had higher low-density lipoprotein fractions and lower triglyceride-rich lipoprotein and high-density lipoprotein fractions than healthy dogs. © 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine

Parental investment and egg yolk lipid composition in gulls.

1. Within-clutch variation in parental investment of yolk lipid (including essential fatty acid composition and fat-soluble vitamin content) was investigated in whole clutches of three eggs of Lesser Black-backed Gulls, Larus fuscus. 2. Although there were no significant differences between years in egg size or yolk mass among eggs of the same laying order, eggs collected in 1996 had significantly lower lipid content than those collected in 1997. 3. In both years third-laid c-eggs were smaller, had a smaller mass of yolk and had significantly lower yolk lipid mass compared with earlier laid (a- and b-) eggs. 4. Despite this lower lipid mass of c-eggs, of the different lipid fractions only cholesterol content of c-eggs was significantly lower than that of a- or b-eggs. 5. Earlier laid eggs had greater amounts of arachidonic acid in the phospholipid and cholesterol ester fractions of yolk lipid, and considerably greater quantities of vitamin E and carotenoids. 6. Conversely, levels of linoleic acid and vitamin A were equalized among eggs of different laying sequence as both these essential nutrients have primarily systemic roles. 7. The probable effect of increased antioxidant (vitamin E and carotenoid) content of earlier-laid eggs is to enhance embryonic and neonatal growth and development, reduce susceptibility to pathogens and increase the ability of the embryo to withstand the oxidative stress associated with hatching. 8. The results suggest that there is maternal bias of essential nutrients to offspring with the highest reproductive value in order to maximize reproductive success