Ann L. Saritelli

Effect of prolonged exercise training without weight loss on high-density lipoprotein metabolism in overweight men

This study examined the effect of exercise training without weight loss on high-density lipoprotein (HDL) metabolism in overweight men. We evaluated HDL metabolism using 125I-radiolabeled autologous HDL in 17 overweight men aged 40 +/- 7 years (mean +/- SD) before and after 1 year of exercise training. Subjects consumed defined diets in a metabolic kitchen during the metabolic studies. They performed endurance exercise under supervision for 1 hour four times weekly and maintained their pretraining body weight. Maximal oxygen uptake (VO2max) increased 27% (P < .001) with exercise training. HDL-cholesterol (HDL-C) and apolipoprotein (apo) A-I increased 10% and 9%, respectively (P < .001 for both), whereas triglycerides and apo B decreased 7% and 10%, respectively (P < .05). Postheparin lipoprotein lipase increased 11% (P = NS). Hepatic triglyceride lipase activity (HTGLA) decreased 12% (P < .05). The fractional catabolic rate (FCR) of HDL protein and of apo A-I decreased 5% and 7%, respectively (P < .05 for both). The synthetic rate of apo A-I increased 13% (P < .01). Increased HDL after exercise training is associated with both decreased HDL protein catabolism and increased HDL apo A-I synthesis. Weight loss is not required to increase HDL-C with exercise training in overweight men, but without weight loss, even prolonged exercise training produces only modest changes in HDL-C concentrations.

Acute decrease in serum triglycerides with exercise: Is there a threshold for an exercise effect?☆

Acute reductions in triglycerides and low density lipoprotein (LDL) cholesterol concentrations have been demonstrated in endurance athletes after prolonged exercise. To determine if similar changes occur in untrained subjects and to determine the duration of exercise necessary for such changes, we measured serum lipids and lipoproteins in 10 sedentary men after 1 hour of exercise at their anaerobic threshold. Findings in sedentary men were compared with those of 9 competitive cyclists after 1 and 2 hr of exercise. LDL cholesterol increased in the cyclists immediately after 1 and 2 hours of exercise. Total cholesterol and high density lipoprotein (HDL) cholesterol also increased in the cyclists immediately after the 2 hr session. These increases were transient and not significant when corrected for changes in plasma volume. Serum triglycerides were unchanged for 4 hr after exercise. By 24 hr, however, triglycerides had decreased in both the trained (17%) and untrained men (22%) after the 1 hr session and in the trained men (33% p < 0.01) after the 2 hr session. These results demonstrate a delayed decrease in triglyceride concentration that is related to the duration of exercise and probably has no distinct threshold. The lower level of triglycerides in endurance athletes and in sedentary subjects after exercise training is due at least in part to an acute exercise effect.

Elevated high-density lipoprotein cholesterol in endurance athletes is related to enhanced plasma triglyceride clearance☆

We compared the clearance rate (K2) of plasma triglycerides (TG) following the intravenous (IV) infusion of a fat emulsion in 13 male endurance athletes (age 33 +/- 5.6 years, mean +/- SD) and 12 sedentary men (33 +/- 5.6 years). The athletes had lower fasting triglycerides (TG) (75 +/- 30.4 mg/dL v 125 +/- 52.5 mg/dL) and higher high-density lipoprotein (HDL) cholesterol concentrations (64 +/- 16.2 mg/dL v 42 +/- 9.4 mg/dL) than the sedentary subjects (P less than .01 for all). The higher HDL concentrations were due to increases in both the HDL2 and HDL3 subfractions. K2 in the athletes was 92% higher than that in the sedentary men (4.8 +/- 2.3%/min v 2.5 +/- 0.7%/min, P less than .01), but there was no difference in postheparin lipoprotein lipase activity (LPLA) between the groups (P greater than .05). K2 was positively correlated with LPLA (r = .51) and inversely related to fasting TG concentrations (r = -.73, P less than .01 for both). Furthermore, K2 was directly related to HDL (r = .75), HDL2 (r = .72), and HDL3 (r = .60) cholesterol concentrations (P less than .01 for all). These data suggest that the low TG levels in endurance athletes result at least in part from increased TG removal and that the elevated HDL concentrations of endurance athletes are related to enhanced fat clearance.

Postheparin plasma lipolytic activities in physically active and sedentary men after varying and repeated doses of intravenous heparin

We sought to determine the optimal dose of heparin for evaluating the activities of lipoprotein lipase (LPLA) and hepatic triglyceride hydrolase (HTGLA) in postheparin plasma. Nine physically active and ten sedentary men (age 30 ± 5 yr, mean ± SD) received 30, 50, 75, and 100 IU/kg of heparin in random order during a 2-week period. Based on all the samples, the average LPLA in the athletes was 43% higher (P < 0.001) and HTGLA was 19% lower than in the untrained subjects (NS). The greatest LPLA was obtained after a heparin dose of 75 IU/kg, but LPLA after the three highest doses were not significantly different. There was also a dose effect on HTGLA (P < 0.001) with greatest activities following doses of 75 and 100 IU/kg. Despite these dose effects, subjects maintained their rank order for both postheparin lipase activities regardless of the heparin dose. The only exception was for LPLA in the sedentary men probably because of lower LPLA and a smaller range of values. We also examined the effect of repeated daily injections of 75 IU/kg heparin on LPLA, HTGLA, and serum lipids. Repeated heparin administration on three consecutive days produced no significant effects on the apparent lipase activities. When all subjects were combined, HDL-cholesterol was increased over time (P < 0.05) due to increases in both the HDL2 (P < 0.05) and HDL3-cholesterol (NS) subfractions. Infusion of heparin or saline on three consecutive days into 18 additional men, however, had no effect on any lipid parameter. We conclude that 75 IU/kg is as effective as 100 IU/kg of heparin for releasing LPLA and HTGLA and that the relative rank for lipase activities among subjects with a wide range of values is not affected by the heparin dose. Repeated heparin injections do not alter postheparin plasma lipase activities or lipid and lipoprotein concentrations measured on subsequent days.

Variations in plasma volume affect total and low-density lipoprotein cholesterol concentrations during the menstrual cycle

Serum lipids are known to vary during the menstrual cycle. To determine if changes in plasma volume contribute to this effect, we determined serum lipids, lipoproteins, and estimated changes in plasma volume in 18 premenopausal women at the start of and at 5-day intervals after menstruation. Eleven men served as a comparison group. Changes in plasma volume were estimated from changes in hemoglobin and hematocrit. Total and low-density lipoprotein (LDL) cholesterol (mean +/- SD) increased 15 +/- 14 mg/dL (9% +/- 10%) and 11 +/- 13 (11% +/- 14%) within 10 days after the start of menstruation (P < .05) and then decreased toward baseline during the rest of the cycle. High-density lipoprotein (HDL) cholesterol increased 3 mg/dL, or 5%, (P < .05) on days 10 and 15 after menstruation. Plasma volume decreased 4% +/- 9% (P < .06) 10 days after the start of menstruation, and this maximum decrease in plasma volume coincided with peak increases in total, LDL, and HDL cholesterol. Except for an 8-mg/dL increase in LDL cholesterol at day 5, lipid changes were no longer significant after adjusting for changes in plasma volume. We conclude that alterations in plasma volume account for approximately half of the increase in total and LDL cholesterol during the menstrual cycle.

Time course of serum amyloid A response in myocardial infarction

Plasma concentrations of serum amyloid A (SAA), high density lipoprotein (HDL) cholesterol, non-HDL cholesterol, and apolipoproteins (Apo) A-I and B were measured daily for 6 days in 10 patients following myocardial infarction (MI) and in 10 secular controls admitted to a coronary care unit. SAA concentrations peaked 3 days following MI (mean 47 mg/dl) and correlated with creatine kinase (CK) (r = 0.67, P less than 0.001). Non-HDL cholesterol and Apo B fell 15 and 18%, respectively, reached nadirs 3-4 days after MI and were inversely related to CK concentrations (P less than 0.01 for both). HDL cholesterol levels, in contrast, increased 15% and were significantly higher than baseline by day 3 when SAA concentrations were maximum. HDL cholesterol subsequently fell in parallel with SAA and had returned to baseline by day 6. Apo A-I declined throughout the 6 days of observation and was 13% lower than initial values on day 6 (P less than 0.05). The Apo A-I reduction was inversely related to both CK and SAA concentrations. There were no significant changes in any of the analytes in control subjects. We conclude that Apo A-I and possibly Apo B containing lipoproteins are negative acute phase reactants. HDL cholesterol is transiently elevated after MI despite decreasing Apo A-I levels and this may relate to incorporation of SAA into HDL particles.

Effects of short-term stanozolol administration on serum lipoproteins in hepatic lipase deficiency.

We have identified a kindred in Providence, RI, deficient in hepatic triglyceride lipase (HL). The two affected brothers have coronary heart disease and elevated levels of triglycerides, total cholesterol, high-density lipoprotein (HDL) cholesterol, and apolipoprotein [apo] A-I. The lipoprotein lipase (LPL) activity is normal. We and others have postulated that the effects of oral anabolic steroids on HDL metabolism are mediated by HL. To test this hypothesis, we treated these two men and two controls with the oral androgen stanozolol (6 mg/d) for 2 weeks. Consistent with other reports, HL activity increased a mean of 277% in controls with a concomitant decrease in HDL cholesterol (49%), HDL2 cholesterol (90%), HDL3 cholesterol (16%), and apo A-I (41%) and no change in apo A-II. Although stanozolol failed to induce HL activity in the HL-deficient man, HDL cholesterol, HDL2 cholesterol, and apo A-I were reduced a mean of 20%, 48%, and 32%, respectively. In contrast to controls, HDL3 cholesterol (46%) and apo A-II (14%) increased in HL-deficient subjects. Stanozolol treatment also increased LPL activity (124% +/- 86%, n = 4) and decreased lipoprotein(a) ([Lp(a)] 66% +/- 3%, n = 3) in the three men with detectable levels. The data indicate that in addition to stimulation of HL activity, stanozolol treatment changes HDL cholesterol concentration and subfraction distribution by other mechanisms.

Nh2-terminal analysis of four of the polymorphic forms of human serum amyloid a proteins

We recently demonstrated that the serum amyloid A proteins (SAA) occur in six related polymorphic forms of indistinguishable molecular weights and COOH-terminal sequence. We have now obtained very homogeneous preparations of four of these proteins and shown that their amino acid compositions are similar but not identical. Two of these, SAA1 and SAA4, have the same 20 NH2-terminal residues despite striking differences in electrophoretic mobility and solution properties. SAA5 and SAA2, respectively, lack one and three of the NH2-terminal residues common to SAA1 and SAA4. The data are consistent with the postulate that some of the SAA polymorphs are products of different genes.