RESUMEN
Serum amyloid A and high density lipoprotein (HDL) interrelationships were evaluated in 11 normal men during an acute phase response induced by the inflammatory steroid etiocholanolone. Compared with baseline, HDL-cholesterol levels were significantly elevated at 30 h but not at 50 h (P less than 0.05) after etiocholanolone. A-apoprotein concentrations were unchanged at 30 h but were reduced at 54 h (P less than 0.01). Four subjects were sampled every 6-8 h for 5 days. Two men had peak SAA concentrations of 30 and 33 mg dl-1. Their A-apoprotein levels declined as SAA rose and remained low even after SAA levels had returned to baseline. High density lipoprotein cholesterol levels did not fall, however, when SAA was increasing, and fell only after SAA levels declined. No changes in HDL-cholesterol or protein were observed in two subjects whose peak SAA concentrations were 10 and 12 mg dl-1. These observations suggest that a threshold level of acute phase response is required before HDL reductions occur. Column chromatography of SAA-rich plasma did not demonstrate the presence of either SAA or A-apoproteins that were unassociated with lipoproteins. Serum amyloid A, moreover, demonstrated little capacity to displace A-proteins from HDL at SAA concentrations typically observed during the acute phase response. We infer from these studies that SAA may substitute for the A-apoproteins and temporarily maintain HDL-cholesterol levels; but that low HDL levels during the acute phase response are likely due to reduced A-protein synthesis rather than displacement by SAA.
Asunto(s)
Reacción de Fase Aguda/sangre , Inflamación/sangre , Lipoproteínas HDL/sangre , Proteína Amiloide A Sérica/fisiología , Reacción de Fase Aguda/inducido químicamente , Adulto , Apolipoproteínas A/sangre , Apolipoproteínas C/sangre , Etiocolanolona/farmacología , Humanos , MasculinoRESUMEN
High-density lipoprotein (HDL) metabolism was studied in eight sedentary men before and after 14 and 32-48 weeks of exercise training. Subjects rode stationary bicycles 1 hour daily, 5 days each week for 14 weeks (n = 8), and 4 days each week thereafter for a total of 32-48 weeks (n = 7) of training. HDL metabolism was assessed with 125I-radiolabeled autologous HDL while subjects consumed defined diets. Maximal oxygen uptake increased 26 +/- 7% (p less than 0.001) after 14 weeks but did not increase further with more prolonged training. Body weight and estimated body fat did not change. HDL cholesterol increased 5 +/- 3 mg/dl, and triglycerides decreased 19 +/- 23 mg/dl after 14 weeks (p less than 0.025 for both), but there were no additional changes with continued training. Postheparin plasma lipoprotein lipase activity was 22% higher than baseline activity after both 14 (p less than 0.025) and 32 or more weeks of exercise. In contrast, hepatic triglyceride lipase activity was 16 +/- 8% and 15 +/- 8% lower than baseline at each measurement (p less than 0.005 for both). The disappearance rate of triglycerides after an intravenously administered fat solution was 24 +/- 24% higher at 14 weeks and 49 +/- 18% (p less than 0.005) higher after more prolonged training. Total and low-density lipoprotein cholesterol and apolipoprotein A-I and A-II concentrations at the end of study were not different from initial values. Plasma volume was 8% above initial values at both post-training measurements. The biological half-life of apolipoprotein A-I was unchanged at 14 weeks but was 10 +/- 13% longer (p = 0.07) and increased in all but one subject at the end of the study. Half-life for apolipoprotein A-II was 8 +/- 8% (p = 0.031) and 11 +/- 14% (p = 0.06) above baseline at 14 and 32 or more weeks, respectively. The synthetic rates for apolipoproteins A-I and A-II were not different from baseline values at 32-48 weeks. We conclude that 8-11 months of exercise training in previously sedentary men enhances fat tolerance and increases HDL cholesterol concentrations by prolonging HDL survival. The changes in HDL apolipoprotein survival, however, do not approximate the differences previously noted between elite endurance athletes and sedentary men. Changes in HDL cholesterol concentration were not large and suggest that the potential for exercise-related changes in HDL may be modest in many subjects.
Asunto(s)
HDL-Colesterol/sangre , Educación y Entrenamiento Físico , Peso Corporal , Dieta , Ingestión de Energía , Metabolismo Energético , Humanos , Lípidos/sangre , Lipoproteína Lipasa/sangre , Masculino , Consumo de Oxígeno , Volumen Plasmático , Factores de TiempoRESUMEN
We describe a child, the issue of phenotypically normal parents, who had fat malabsorption, both intestinal and hepatic steatosis, and serum cholesterol and triglyceride concentrations of 38 and 63 mg/dl, respectively. Lipoprotein electrophoresis, Ouchterlony double diffusion, and electron microscopy demonstrated that normal low density lipoproteins (LDL: 1.006 less than rho less than 1.063 g/ml) were absent. Lipoprotein particles in the rho less than 1.006-g/ml fraction were triglyceride rich, very large (93.2 +/- 35.1 nm), and contained the B-48 but not the B-100 apoprotein; both species of apolipoprotein (apo) B were found in the parents' lipoproteins. These chylomicrons and chylomicron remnants were present even in the patient's fasting plasma, which suggested prolonged dietary fat absorption. Plasma levels of high density lipoprotein lipids and proteins were low, and the phosphatidylcholine/sphingomyelin ratio was reduced as in typical abetalipoproteinemia. The monosialylated form of apo C-III was not identified on polyacrylamide gel electrophoresis, which suggested that this protein was elaborated only with very low density lipoproteins (VLDL). A radioimmunoassay for apo B employing a polyclonal antisera to plasma LDL gave apparent plasma apo B levels of 0.6, 66, and 57 mg/dl in the patient and his father and mother, respectively. The displacement curve generated by the parents' VLDL and LDL did not did not differ from control lipoproteins. The patient's chylomicron-chylomicron remnant fraction displaced normal LDL over the entire radioimmunoassay range, but the efficiency of displacement was strikingly less than with B-100 containing lipoproteins. If the patient's B-48 protein is not qualitatively abnormal, these results confirm very limited immunochemical cross-reactivity between at least one major epitope on B-100 and the epitopes expressed on B-48. The apo B defect in this patient appears to be recessive. It abolishes B-100 production and may additionally limit the formation of B-48.
Asunto(s)
Apolipoproteínas B/biosíntesis , Apolipoproteínas B/deficiencia , Síndromes de Malabsorción/metabolismo , Adulto , Apolipoproteína B-100 , Apolipoproteína B-48 , Biopsia , HDL-Colesterol/sangre , Electroforesis en Gel de Agar , Electroforesis en Gel de Poliacrilamida , Femenino , Humanos , Lactante , Intestino Delgado/patología , Lipoproteínas LDL/sangre , Hígado/patología , Masculino , Microscopía ElectrónicaRESUMEN
We studied the high-density lipoprotein (HDL) metabolism of five trained men who ran 16 km daily and five inactive men. Runners were leaner and their aerobic exercise capacity was much greater. The mean HDL cholesterol level was 65 mg/dL in the runners and 41 mg/dL in the controls. The lipid-rich HDL2 species accounted for a much higher proportion of the HDL in runners (49% v 29%). Tracer studies of radioiodinated autologous HDL demonstrated that runners did not produce more HDL protein but rather catabolized less. The mean biologic half-life of HDL proteins was 6.2 days in the runners compared with 3.8 days in the sedentary men. The activity of lipoprotein lipase was 80% higher in the postheparin plasma of the runners, whereas the activity of hepatic triglyceride hydrolase was 38% lower. Thus, the prolonged survival of plasma HDL proteins in runners may result from augmented lipid transfer to HDL by lipoprotein lipase or diminished HDL clearance by hepatic lipase.