Linda L. Bausserman

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.

The effect of testosterone aromatization on high-density lipoprotein cholesterol level and postheparin lipolytic activity☆

Stanozolol, an oral 17 alpha-alkylated androgen, increases hepatic triglyceride lipase activity (HTGLA) and decreases high-density lipoprotein cholesterol (HDL-C) levels, whereas intramuscular testosterone has comparatively little effect. In the present study, we tested the hypothesis that aromatization of androgen to estrogen blunts the lipid and lipase effects of exogenous testosterone. Fourteen male weightlifters received testosterone enanthate (200 mg/wk intramuscularly), the aromatase inhibitor testolactone (250 mg four times per day), or both drugs together in a randomized cross-over design. Serum testosterone level increased during all three drug treatments, whereas estradiol level increased only with testosterone alone (+47%, P < .05), demonstrating that testolactone effectively inhibited testosterone aromatization. Testosterone decreased HDL-C(-16%, P < .05), HDL2-C(-23%, NS), and apoprotein (apo) A-I (-12%, P < .05) levels, effects that were consistently but not significantly greater with simultaneous testosterone and testolactone administration (HDL-C, -20%; HDL2-C, -30%; apo A-I, -15%; P < .05 for all). In contrast, both testosterone regimens decreased HDL3-C levels by 13% (P < .05 for both). HTGLA increased 21% during testosterone treatment and 38% during combined testosterone and testolactone treatment (P < .01 for both). Lipoprotein lipase activity (LPLA) increased only during combined testosterone and testolactone treatment (+31%, P < .01), suggesting that estrogen production may counteract the effects of testosterone on LPLA. Testolactone alone had little effect on any lipid, lipoprotein, apoprotein, or lipase concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

C-reactive protein, but not homocysteine, is related to cognitive dysfunction in older adults with cardiovascular disease

Cardiovascular disease (CVD) is a risk factor for cognitive impairment and dementia. Recent studies implicate homocysteine (HCY) and C-reactive protein (CRP) in this increased risk, as both are associated with cognitive dysfunction in demented and non-demented patients. However, it remains unclear whether they confer added risk in older adults with CVD. A total of 126 older CVD patients underwent blood and neuropsychological evaluation as part of a prospective examination of the neurocognitive consequences of CVD. A subset of these participants (n=37) also underwent neuroimaging to quantify the degree of white matter disease. After adjusting for demographic and medical factors, no significant relationship emerged between HCY and cognitive performance. In contrast, CRP showed significant independent relationships to test performance, including global cognitive performance, attention/psychomotor function, executive function, memory, and visuospatial abilities. Neither HCY nor CRP was related to extent of white matter disease or whole brain volume on magnetic resonance imaging. Further study is needed to identify mechanisms by which inflammatory processes impact on cognitive function and to determine whether reducing circulating levels of inflammatory markers results in improved cognition.

Exercise training has little effect on HDL levels and metabolism in men with initially low HDL cholesterol

Low concentrations of high-density lipoprotein cholesterol (HDL-C) are a recognized risk factor for atherosclerotic cardiovascular disease. Exercise is often recommended to increase HDL-C, but the effect of exercise training on HDL levels and metabolism in subjects with low HDL concentrations is not well defined. The present study compared the HDL response to 12 months of supervised endurance exercise training without weight loss in 17 men aged 26 49 years with initially low ( < 40 mg/dl, N=7) or normal ( > 44 mg/dl, N=10) HDL-C levels. HDL-C levels and HDL apolipoprotein metabolism were assessed while the subjects consumed controlled diets before and after the year of training. Increases in total (5.1+/-2.8 versus 1.9+/-4.2 mg/dl, P=0.08) and HDL2 (3.8+/-2.9 versus 0.4+/-1.1 mg/dl, P=0.01) cholesterol were greater in men with normal initial HDL-C levels. Catabolic rates for HDL apolipoproteins decreased 7-14% and biological half-lives increased 10-15% after exercise training in subjects with normal HDL, but were unchanged in the low HDL-C group. HDL apolipoprotein synthetic rates were not consistently affected by exercise training in either group. Postheparin lipoprotein lipase activity increased 27%, the clearance rate of intravenous triglycerides increased 14%, and apolipoprotein B levels decreased 16% with training in subjects with normal HDL-C but were unchanged in the low HDL-C group. We conclude that the ability to increase HDL-C levels through endurance exercise training is limited in subjects with low initial HDL-C, possibly because exercise training in such subjects fails to alter triglyceride metabolism.

Acute psychological stress reduces plasma triglyceride clearance.

Acute stress elevates blood lipids, with the largest increases among men and postmenopausal women. The mechanisms for the effect are unknown, but may be due to altered lipid metabolism. This study investigated if acute stress induces transient reductions in triglyceride clearance in middle-aged men and women, and determined if gender and menopause affect triglyceride metabolism. Of the 35 women, half were premenopausal, and half were naturally postmenopausal; men (n = 35) were age matched. Clearance of an intravenously administered fat emulsion was assessed twice: once during a nonstress session, and again during a stress-testing session. During the stress session, a battery of behavioral stressors (serial subtraction, speech, mirror tracing, and Stroop) were performed for 40 min. The clearance rate of exogenous fat was significantly diminished during the stress, relative to the nonstress session. Women had more efficient clearance, relative to men, but there were no effects of menopausal status. The diminished ability to clear an intravenous fat emulsion during stress suggests one mechanism for stress-induced elevations in lipids.

Testosterone decreases lipoprotein(a) in men.

We administered testosterone, with or without the aromatase inhibitor testolactone, to determine the effects of testosterone and its aromatization to estradiol on Lp(a) levels in normal men. Average Lp (a) values decreased by 37% during testosterone alone and by 28% when testosterone and testolactone were combined, suggesting that testosterone reduces Lp(a) in men primarily by an androgenic effect and not by its conversion to estradiol.

Population change in adult obesity and blood lipids in American Samoa from 1976-1978 to 1990

Obesity in American Samoan adults in 1990 was compared to that in 1976–1978 to evaluate population changes concomitant with modernization. Body weight, stature, the body mass index (BMI), and two skinfolds were measured in 1990 in 830 males and females 25–74 years old, and were compared to corresponding data from 1976 and 1978 for 1,621 adults. Mean BMI and skinfold thicknesses increased markedly from 1976–1978 to 1990 in males at all ages. Mean BMI for 45–54 year old males was approximately 3.6 kg/m2 higher (P < 0.0001) in 1990 than in 1976–1978, but was only 0.6 kg/m2 higher in females of the same age. The prevalence of overweight increased significantly from 66% in 1976–1978 to 85% in 1990 (P < 0.001) in 35–44 year old males, but remained about the same, 91%, in females of that age. Similar sex differences in temporal change were found in skinfolds. Fasting serum total and high density lipoprotein (HDL) cholesterol and triglycerides were obtained for a random subsample of 67 males 40–49 years old and were compared to lipid levels in a 1978 sample of American Samoan males of similar age and residence. Both total and HDL cholesterol were significantly different between 1978 and 1990, 178 vs. 205 mg/dl (P < 0.02), and 43 vs. 37 mg/dl (P < 0.01), respectively. Triglycerides were higher in 1990 than in 1978, 169 vs. 128 mg/dl. The results suggest that obesity and adiposity increased more over 12–14 years among adult males than among females, who in 1976–1978 were already massively overweight.

Lipoprotein Lipase Activity and Plasma Triglyceride Clearance Are Elevated in Endurance-Trained Women

Numerous studies have examined factors regulating high-density lipoprotein cholesterol (HDL-C) levels in male endurance athletes, but few studies have examined HDL-C regulation in female athletes. The present study compared lipid and lipoprotein concentrations, postheparin lipolytic activities, and the clearance rate (K2) of triglycerides following an intravenous fat infusion in 12 female distance runners (aged 33 ± 9 years, mean ± SD) and 13 sedentary women (33 ± 9 years). Runners were leaner and had greater maximum oxygen uptake values than controls. Runners also had nonsignificantly lower triglyceride (53 ± 15 v 65 ± 13 mg/dL) and higher HDL-C (62 ± 14 v 52 ± 8 mg/dL, P = .06). Lipoprotein lipase activity (LPLA) was 33% greater (P < .05) and fat clearance (K2) was 27% faster (P < .01) in the trained women, and LPLA correlated directly with K2 (r = .61) and HDL-C (r = .62) in this group (P < .05 for both). K2 was directly related to HDL-C in the athletes (r = .57, P = .06), and also when the active and sedentary women were combined (r = .43, P < .05). These results suggest that increased LPLA and enhanced plasma triglyceride clearance may contribute to the HDL-C levels of physically active premenopausal women.

Rapid clearance of serum amyloid A from high-density lipoproteins

The serum amyloid A proteins (SAA) occur in plasma in six polymorphic forms that are associated with the high-density lipoproteins (HDL). We studied two of the SAA proteins, SAA1 and SAA4, which have the same amino- and carboxy-terminal residues but different solution properties and electrophoretic mobilities, to determine whether they are interconverted in plasma in vivo. They were radioiodinated in vitro, incorporated into HDL, and administered to cynomolgus monkeys. Both remained associated with HDL for at least 6 h, had similar plasma die-away curves, and retained their characteristic electrophoretic mobilities, suggesting they are not related as precursor and product. The plasma clearance of the most prevalent SAA species, SAA4, was also simultaneously compared with the human A-I and C-III-2 apolipoproteins. Human apolipoprotein A-I decayed from plasma at a rate comparable to that of monkey HDL proteins. Apolipoprotein C-III-2 was cleared more rapidly and SAA4 at an even greater rate. These findings suggest that SAA are either dissociated from HDL before clearance from plasma or that SAA are contained in an HDL subspecies with metabolic fate different from that of most HDL particles.

Serum amyloid A and high density lipoproteins during the acute phase response

Abstract. 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 < 0·05) after etiocholanolone. A‐apoprotein concentrations were unchanged at 30 h but were reduced at 54 h (P < 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.