Effect of estrogen on post-heparin lipolytic activity. Selective decline in hepatic triglyceride lipase.

The rise in plasma triglyceride (TG) levels associated with estrogen administration has been thought to arise from impaired clearance because of the uniform suppression of post-heparin lipolytic activity (PHLA). Recently PHLA has been shown to consist of two activities: hepatic TG lipase and extrahepatic lipoprotein lipase (LPL). To determine whether estrogen might induce a selective decline in one of these activities, both hepatic TG lipase and extrahepatic LPL were measured in post-heparin plasma from 13 normal women before and after 2 wk of treatment with ethinyl estradiol (1 mug/kg per day). Hepatic TG lipase and extrahepatic LPL were determined by two techniques: (a) separation by heparin-Sepharose column chromatography, and (b) selective inhibition with specific antibodies to post-heparin hepatic TG lipase and milk LPL. Estrogen uniformly depressed hepatic TG lipase as measured by affinity column (-68 +/- 12%, mean +/- SD, P less than 0.001) or antibody inhibition (-63 +/- 11%, P less than 0.001). Extrahepatic LPL was not significantly changed by affinity column (-22 +/- 40%) or antibody inhibition (-3 +/- 42%). Direct measurement of adipose tissue LPL from buttock fat biopsies also showed no systematic change in the activated form of LPL measured as heparin-elutable LPL (+64 +/- 164%) or in the tissue form of LPL measured in extracts of acetone-ether powders (+21 +/- 77%). The change in hepatic TG lipase correlated with the change in PHLA (r = 0.969, P less than 0.01). However, neither the change in PHLA nor hepatic TG lipase correlated with the increase in TG during estrogen. The decrease in PHLA during estrogen thus results from a selective decline in hepatic TG lipase.

Reduced LPL and subcutaneous lipid storage capacity are associated with metabolic syndrome in postmenopausal women with obesity.

OBJECTIVES: This study examines the hypothesis that lower adipose tissue lipoprotein lipase (LPL) activity and a limited capacity for subcutaneous adipocyte expansion will be associated with metabolic syndrome (MSyn) in postmenopausal women who are overweight and obese. METHODS: Women (N = 150; age 60 ± 1 year; BMI: 31.5 ± 0.3 kg m-2; mean ± standard errors of the means [SEM]) with and without MSyn had dual-energy X-ray absorptiometry scans for total body fat, CT scans for visceral and subcutaneous abdominal adipose tissue areas, lipid and glucose metabolic profiles, and abdominal and gluteal fat aspirations for subcutaneous fat cell weight (FCW; N = 150) and LPL activity (N = 100). RESULTS: Women with MSyn had similar total body fat, but 15% larger abdominal and 11% larger gluteal FCWs and more visceral fat (179 ± 7 vs. 134 ± 6 cm2) than women without MSyn (P's < 0.05). Abdominal LPL activity was 13% (P = 0.18) lower in women with than without MSyn and correlated with abdominal FCW (r = 0.49, P < 0.01) only in those without MSyn. Visceral fat and abdominal and gluteal FCWs correlated with MSyn components, and subcutaneous adipose tissue correlated with abdominal FCW (r = 0.43, P < 0.01) and LPL activity (r = 0.18, P < 0.05), independent of total body fat. CONCLUSIONS: These results show that women with MSyn have lower LPL activity, limited capacity for subcutaneous adipocyte lipid storage and greater ectopic fat accumulation in viscera than women without MSyn of comparable obesity. This suggests that the development of novel therapies that would enhance adipocyte expandability might prevent the accumulation of ectopic fat and reduce the risk for MSyn in postmenopausal women with obesity.

Limited value of the homeostasis model assessment to predict insulin resistance in older men with impaired glucose tolerance.

OBJECTIVE: Insulin resistance (IR) in older individuals is associated with risk factors for coronary artery disease. The glucose clamp measures IR directly, but the homeostasis model assessment (HOMA) of IR, referred to here as HOMA-IR, is based on fasting glucose and insulin and is less invasive and labor intensive. This method requires validation in the elderly. RESEARCH DESIGN AND METHODS: We assessed the validity of HOMA-IR as an index of IR by comparing it to glucose infusion rates (GIRs) measured by a glucose clamp (600 pmol x m(-2) x min(-1)) in 45 obese men (61 +/- 8 years of age, mean +/- SD) with normal glucose tolerance (NGT) (n = 21) or impaired glucose tolerance (IGT) (n = 24). We also evaluated relationships between body composition, exercise capacity, and IR. RESULTS: Subjects with NGT had lower BMI (28 +/- 3 vs. 31 +/- 3 kg/m2), waist circumference (97 +/- 9 vs. 105 +/- 9 cm), waist-to-hip ratio (WHR) (0.93 +/- 0.06 vs. 0.97 +/- 0.05), and percent body fat (25 +/- 6 vs. 30 +/- 6) than subjects with IGT. Subjects with NGT also had lower areas above basal during the 2-h oral glucose tolerance test for glucose (274 +/- 95 vs. 419 +/- 124 mmol x min/l) and insulin (38,142 +/- 18,206 vs. 58,383 +/- 34,408 pmol x min/l) and lower HOMA-IR values (2.2 +/- 0.8 vs. 4.2 +/- 2.6) than subjects with IGT. GIR (micromol x kg(-1) FFM x min(-1)) was higher in subjects with NGT than in subjects with IGT (53 +/- 11 vs. 43 +/- 14). HOMA-IR correlated with GIR in subjects with NGT (r = -0.59), but not in subjects with IGT (r = -0.13). GIR correlated with VO2max in subjects with NGT (r = 0.58) and IGT (r = 0.42), but with WHR only in subjects with NGT (r = -0.53). HOMA-IR correlated with VO2max (r = -0.57) and waist circumference (r = 0.54) in subjects with NGT, but with percent body fat in subjects with IGT (r = 0.54). CONCLUSIONS: These findings indicate that HOMA-IR should not be used as an index of IR in older individuals who may be at risk for IGT, and suggest that lifestyle changes that increase VO2max and decrease body fat may reduce IR in older people.

Reversal of decreased human adipose tissue lipoprotein lipase and hypertriglyceridemia after treatment of hypothyroidism.

To determine whether adipose tissue lipoprotein lipase (LPL) plays a role in the regulation of triglyceride (TG) metabolism in hypothyroidism, the activity of the enzyme was measured in the subcutaneous adipose tissue of six hypothyroid patients before and during therapy with L-thyroxine. The activity of the activated form of the enzyme, measured as heparin elutable LPL, was lower in hypothyroid patients (1.54 +/- 0.93; mU/10(6) cells; mean +/- SD) than in controls (3.26 +/- 1.49; P less than .02) and increased (163 +/- 89%; P less than .01) with treatment to levels comparable to the controls. The total activity of LPL, measured in ammonium hydroxide extracts of acetone ether tissue powders, was in the low normal range in the hypothyroid patients (0.68 +/- 0.42), but not significantly different from normal (1.10 +/- 0.58) and did not increase significantly (92 +/- 105%), with treatment. Plasma post heparin lipolytic activity (PHLA) was low in hypothyroidism and increased (111 +/- 78%; P less than .05) with treatment. These increases in PHLA correlated with the increases in the activity of heparin elutable LPL (r = .88, P less than .05). In all patients fasting plasma TG levels decreased (-43 +/- 25%; P less than .02) after treatment. Serial determination of heparin elutable LPL activity, PHLA, and plasma TG during L-thyroxine treatment revealed a correlation between the per cent changes in PHLA and heparin elutable LPL activity (r = .68, P less than .05), an inverse correlation between plasma TG levels and heparin elutable LPL (r = -0.53,P less than .05) and no correlation between plasma TG and PHLA (r = -0.05). These results suggest that the low PHLA and hypertriglyceridemia of hypothyroidism are related to low adipose tissue LPL activity. All these parameters return to normal after treatment with L-thyroxine and attainment of euthyroidism.

Selective osmoreceptor dysfunction in the syndrome of chronic hypernatremia.

A patient with the syndrome of chronic hypernatremia (serum Na+: mean = 154, range 139-184 mEq/l, n = 30) and hypodipsia due to a hypothalamic injury was studied to evaluate osmolar and baroreceptor control of arginine vasopressin (AVP) secretion. Resting plasma AVP levels measured by radioimmunoassay were inappropriately low for the degree of plasma hyperosmolality: range = less than 0.5-2.1 pg/ml, n = 10, with corresponding levels of plasma osmolality (P osM) greater than 300 m osmol/kg, suggesting either direct damage to the AVP synthesis and storage area or impaired afferent osmoreceptor function. Direct pituitary damage seemed unlikely, since anterior pituitary function was normal by standard testing. The existence of adequate neurohypophyseal stores of AVP was demonstrated by baroreceptor stimulation with the hypotensive agent trimethaphan (Arfonad): plasma AVP rising to 50.0 pg/ml during transient hypotension (BP = 70/0). Osmoreceptor function was evaluated during acute water loading followed by hypertonic saline infusion. During hypertonic saline infusion plasma AVP levels correlated with P osM (R = .87, P less than .01, n = 8), suggesting some residual osmotic regulation of AVP release. The osmotic threshold for AVP release (the x-axis intercept of the plasma AVP-P osM regression line) was not higher than normal. However, the AVP levels throughout this study remained markedly subnormal for the degree of plasma hyperosmolality (maximum plasma AVP = 1.9 PG/ML when P os M = 327 M OSMOL/KG). Since a substantial amount of AVP was released with baroreceptor stimulation, the inadequate rise in plasma AVP level with hyperosmolality indicates that afferent input from the osmoreceptor/thirst area of the hypothalamus is selectively impaired in this patient. These findings directly demonstrate a dissociation of osmoreceptor function from the AVP secretory apparatus in man.

Role of body fat distribution in the decline in insulin sensitivity and glucose tolerance with age.

The relationships of body composition and physical fitness [maximal aerobic capacity (VO2max)] to the decline in insulin sensitivity with age were examined in healthy older (47-73 yr; n = 36) and young (19-36 yr; n = 13) men. In 18 older men with normal glucose tolerance (OGTT), glucose disposal rates (M) during hyperinsulinemic euglycemic clamps correlated negatively with the waist to hip ratio (WHR; r = -0.77; P < .001) and percent body fat (r = -0.46; P < 0.05) and positively with VO2max (r = 0.54; P < 0.05), but not with age. Similar relationships existed in the 36 older men with a spectrum of OGTT responses; however, only WHR was independently related to M (r2 = 0.32; P < 0.01). In the older men with normal OGTT, M (mean +/- SEM, 7.88 +/- 0.43 mg/kg fat-free mass.min) was not different from that in the young men (8.56 +/- 0.47; P = NS). Furthermore, in older and young men with normal OGTT matched for WHR, percent fat, or VO2max, glucose disposal was comparable at sequential 15-min intervals during the clamp and in its relationship to insulin concentrations at the tissue level (multicompartmental analysis). In contrast, despite higher steady state plasma insulin levels during the clamp, M was significantly lower in the older men with a higher WHR, greater percent fat, lower VO2max, or impaired OGTT. Thus, in healthy older men up to the age of 73 yr, insulin sensitivity and glucose tolerance are affected primarily by the regional body fat distribution, not age, obesity, or VO2max.

Racial differences in plasma leptin concentrations in obese postmenopausal women.

Leptin may play an important role in the regulation of body weight by influencing energy intake and expenditure. Differences in body composition, resting energy expenditure (REE), and physical activity between African-American and Caucasian women could be reflective of racial differences in plasma leptin concentrations. Thus, we examined racial differences in leptin levels and the relationships of leptin to body composition and resting metabolism in obese postmenopausal African-American (n = 28) and Caucasian (n = 29) women matched for level of body fat. African-American and Caucasian women were similar in age (64.1 +/- 1.3 vs. 63.2 +/- 1.0 yr), body weight (84.7 +/- 3.3 vs. 80.4 +/- 1.3 kg), adipose tissue mass (39.7 +/- 2.8 vs. 38.0 +/- 1.0 kg), waist to hip ratio (0.81 +/- 0.02 vs. 0.81 +/- 0.01), and maximal aerobic capacity (1.5 +/- 0.05 vs. 1.6 +/- 0.05 L/min). African-American women had greater lean tissue mass than Caucasian women (41.8 +/- 1.1 vs. 39.3 +/- 0.6 kg; P = 0.05). The leptin concentration was 20% lower in African-American than Caucasian women (36.0 +/- 4.8 vs. 45.8 +/- 3.5; P < 0.05), whereas REE values were similar. Leptin correlated strongly with percent body fat in African-American (r = 0.71; P < 0.0001) and Caucasian women (r = 0.61; P < 0.001) and with REE in African-American (r = 0.58; P < 0.001), but not Caucasian, women (r = 0.08). These findings suggest racial differences in plasma leptin levels and in leptin's role in the regulation of REE, which may play a role in the greater incidence of obesity in the African-American compared to the Caucasian population.

Impaired insulin sensitivity and maximal responsiveness in older hypertensive men.

This study examines the relation between blood pressure and insulin resistance in obese, sedentary middle-aged and older men. Eleven hypertensive and 17 normotensive subjects of comparable age (58.6 +/- 1.0 years, mean +/- SEM), percent body fat (27.7 +/- 0.7%), and maximal aerobic capacity (30.2 +/- 0.9 mL.kg-1.min-1) participated in this study. Glucose disposal (M, milligrams per kilogram of fat-free mass per minute) determined during a three-dose hyperinsulinemic euglycemic clamp was lower in the hypertensive than normotensive subjects at the low (M at 120 pmol/m2.min: 2.3 +/- 0.2 versus 3.2 +/- 0.3, P = .06), intermediate (M at 600 pmol/m2.min: 8.0 +/- 0.6 versus 10.4 +/- 0.6, P = .02), and high (M at 3000 pmol/m2.min: 13.5 +/- 0.5 versus 15.5 +/- 0.7, P = .04) insulin infusion rates. The calculated insulin concentration necessary for a half-maximal effect (EC50) was greater in the hypertensive than normotensive subjects (1164 +/- 168 versus 864 +/- 66 pmol/L, P = .03). In this population of normotensive and hypertensive men, systolic, diastolic, and mean arterial blood pressures were related to glucose disposal at these insulin infusion rates (r = -.35 to -.46, P < .05) as well as the EC50 (r = .42 to .44, P < .05). Thus, hypertensive obese, sedentary older men have a reduction in both sensitivity and maximal responsiveness to insulin that is directly related to the severity of hypertension independent of obesity and physical fitness.

Salt-induced increases in systolic blood pressure affect renal hemodynamics and proteinuria.

Nine white and 13 black hypertensive patients with normal serum creatinine were randomized to receive either 2 weeks of a low-salt (40 mEq Na+/d) or high-salt (200 mEq Na+/d) diet followed by 2 weeks of the other diet separated by a 1-week washout on their regular diet. The entire study was conducted in an outpatient setting with intensive dietary instruction and monitoring of blood pressure and 24-hour collections of urine for analysis. Urine electrolyte measurement showed that the patients were able to achieve only a modestly reduced (100 +/- 14 mEq Na+/24 h [mean +/- SEM]) low-salt diet as outpatients, while the higher-salt diet (236 +/- 22 mEq Na+/24 h) was more easily achieved. Eleven patients (8 black, 3 white) were classified as modestly salt sensitive on the basis of an increase or decrease in mean arterial pressure of > or = 3 mm Hg going from lower- to high- or high- to lower-salt diets, respectively. In the salt-sensitive patients, the increase in dietary salt intake increased glomerular filtration rate by 29% (71.2 +/- 6.6 to 85.8 +/- 7.3 mL.min-1.1.73 m2, P = .05), with no significant change in renal plasma flow (412.7 +/- 36.4 to 399.6 +/- 27.8 mL.min-1.1.73 m2). There were no changes in these parameters in the salt-resistant patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin resistance, elevated glomerular filtration fraction, and renal injury.

The development of insulin resistance may be an early step in the development of hypertension; however, the mechanism for this process is not known. The worsening of insulin resistance and hypertension could increase both systemic and glomerular capillary pressures and predispose an individual to renal injury. The purpose of this study was to examine the relationship of insulin resistance to glomerular hemodynamics and dietary salt intake in 10 older (68 +/- 6 years), obese (body mass index, 31 +/- 4 kg/m2), mildly hypertensive (151 +/- 8/82 +/- 2 mm Hg), sedentary subjects without clinical evidence of diabetes or renal disease. They were studied on separate days with radioisotopic renal clearances (glomerular filtration rate by 99mTc-diethylenetriaminepentaacetic acid urinary clearance; renal plasma flow by 131I-hippuran serum disappearance) and a two-dose (40 and 100 mU/m2 per minute) hyperinsulinemic euglycemic clamp for measurement of glucose disposal after 2 weeks of a 3-g and 2 weeks of a 10-g sodium diet. Glomerular filtration rate (68.1 +/- 7.7 to 78.0 +/- 6.6 mL/min per 1.73 m2, P = .08) and glomerular filtration fraction (0.21 +/- 0.02 to 0.22 +/- 0.02, P = .5) did not change significantly after dietary salt was increased. During low dietary salt intake, there was an inverse relationship between glomerular filtration fraction and glucose disposal rate (milligrams per kilogram fat-free mass per minute) at both low (r = -.70, P = .04) and high (r = -.83, P = .006) insulin levels. However, these relationships were attenuated during salt loading. This suggests that a greater degree of insulin resistance, not increased dietary salt, may predispose older mildly hypertensive subjects to renal injury by worsening renal hemodynamics through the elevation of glomerular filtration fraction and resultant glomerular hyperfiltration.

Racial disparities in metabolism, central obesity, and sex hormone-binding globulin in postmenopausal women.

Increased total and intraabdominal fat (IAF) obesity as well as other metabolic conditions associated with the insulin resistance syndrome (IRS) are related to low levels of sex hormone-binding globulin (SHBG) in young and older Caucasian (CAU) and young African-American (AA) women. We examined whether postmenopausal AA women, a population with a high incidence of obesity and IRS despite low IAF, would have higher levels of circulating SHBG compared with CAU women, and whether there would be negative relationships between indexes of obesity and risk factors associated with IRS and SHBG levels. We measured body composition, SHBG, free testosterone, leptin, glucose tolerance, insulin, and lipoprotein lipids in 55 CAU (mean +/- SD, 59 +/- 7 yr) and 35 AA (57 +/- 6 yr) sedentary women of comparable obesity (48% body fat, by dual energy x-ray absorptiometry). Compared with CAU women, AA women had larger waist (101 vs. 96 cm), larger fat mass (44.9 +/- 8.8 vs. 39.9 +/- 8.1 kg), larger sc fat area (552 +/- 109 vs. 452 +/- 109 cm(2)), and lower IAF/SC ratio (0.28 +/- 0.12 vs. 0.38 +/- 0.15; P < 0.01), but similar waist to hip ratio (0.83). Both groups had similar SHBG (117 vs. 124 nmol/L) and free testosterone (3.7 vs. 3.4 pmol/L) levels, but AA women had a 35% higher leptin, 34% higher fasting insulin, and 39% greater insulin response to a glucose load (P < 0.05) compared with CAU women. In CAU, but not AA, women SHBG correlated negatively with body mass index (r = -0.28; P < 0.05), waist (r = -0.36; P = 0.01), IAF (r = -0.34; P = 0.01), and insulin response to oral glucose (r = -0.37; P < 0.05) and positively with high density lipoprotein cholesterol (r = 0.30; P = 0.03). The relationship between insulin area and SHBG in CAU women disappeared after adjusting for IAF, whereas the relationship between high density lipoprotein cholesterol and SHBG persisted after adjusting for IAF, but not for fat mass. Leptin was positively related to fat mass (P < 0.05) in both groups, but it was related to insulin only in the Caucasian women (P< 0.01). There was a racial difference in the slopes (P< 0.05) of the relationships of leptin to fat mass (P < 0.05). Racial differences in leptin disappeared after adjustment for fasting insulin. These results suggest that the metabolic relationships between total and regional obesity, glucose, and lipid metabolism with SHBG in CAU women are different from those in postmenopausal obese AA women.

Control of clofibrate toxicity in uremic hypertriglyceridemia.

A daily dose of 1.5 to 2.0 gm of clofibrate lowers serum triglyceride (TG) levels in patients with normal renal function but causes muscle toxicity and elevated creatine phosphokinase (CPK) levels in patients with long-term renal failure. Plasma clofibrate disappearance is prolonged as much as seven times normal in severely uremic patients. A marked reduction in the standard 14 gm/wk clofibrate dose to a total dose of 1.0 to 1.5 gm/wk effectively lowered serum TG levels (--28%, p less than 0.02) in hypertriglyceridemic hemodialysis patients without toxicity. The serum clofibrate level at this dose was comparable to that in hypertriglyceridemic nonuremic patients receiving 14 gm/wk of clofibrate. The dose of clofibrate administered to hemodialysis patients can be adjusted to avoid toxicity and provide the desired therapeutic effect by monitoring serum CPK and TG levels.

Effect of an American Heart Association diet, with or without weight loss, on lipids in obese middle-aged and older men.

Forty-two obese [body mass index (kg/m2): 30 +/- 5; weight: 92.9 +/- 10.1 kg] men aged 60 +/- 9 y were recruited to determine the effects of an American Heart Association (AHA) diet, with and without weight loss, on lipoprotein lipids. All subjects entered a 3-mo, weight-maintaining AHA diet followed by either a 9-mo weight-loss (AHA + WL, n = 28) or a 9-mo AHA plus weight-maintenance (AHA + WM, n = 14) intervention. Baseline diets were high in fat (35 +/- 6% of energy) and cholesterol (380 +/- 158 mg/d), and low in dietary fiber (18 +/- 5 g/d). The 3-mo AHA diet resulted in an 11% decrease in plasma triacylglycerol (1.83 +/- 0.15 to 1.47 +/- 0.08 mmol/L, P < 0.05), a 16% decrease in plasma cholesterol (5.39 +/- 0.96 to 4.56 +/- 0.91 mmol/L, P = 0.0001), a 17% decrease in high-density-lipoprotein (HDL) cholesterol (1.09 +/- 0.23 to 0.91 +/- 0.18 mmol/L, P = 0.0001), and a 14% decrease in low-density-lipoprotein (LDL) cholesterol (3.47 +/- 0.83 to 2.98 +/- 0.78 mmol/L, P = 0.0001) The AHA + WL group lost 9.8 +/- 4.3 kg (P < 0.001, n = 28) and further reduced plasma triacylglycerol by 17% (P < 0.05), total cholesterol by 4% (P < 0.05), LDL cholesterol by 7% (P < 0.05), and significantly increased HDL cholesterol by 15% (P < 0.05) when compared with their 3-mo AHA-intervention values. These changes were significant (P < 0.05) when compared with the AHA + WM group, in whom lipoprotein lipids did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Visceral adiposity is associated with increased lipid oxidation in obese, postmenopausal women.

Lipolysis is increased in upper-body obese individuals but it is unclear whether body fat distribution is associated with differences in resting metabolic rate (RMR) and/or substrate oxidation in older women. This study determined whether RMR and lipid oxidation are higher in postmenopausal women with visceral obesity. A single-slice computed tomography scan was taken midway between L4 and L5 in 29 women aged 52-72 y with a fat mass of 29.2-68.8 kg. RMR and lipid oxidation rates were measured by using indirect calorimetry. RMR was related to waist circumference (r = 0.45, P < 0.05), but not to waist-hip ratio (WHR; r = 0.23) or intraabdominal fat area (r = 0.26). However, there was a strong, positive relation between lipid oxidation and intraabdominal fat area (r = 0.57, P < 0.01), waist circumference (r = 0.54, P < 0.01), and WHR (r = 0.42, P < 0.05). These correlations remained significant after statistical adjustment for total fat and fat-free mass. These results suggest that in postmenopausal women higher amounts of intraabdominal fat are associated with an enhanced rate of lipid oxidation independent of total adiposity, but not with alterations in RMR.

Effects of an American Heart Association diet and weight loss on lipoprotein lipids in obese, postmenopausal women.

The sequential effects of an American Heart Association (AHA) Step 1 diet and subsequent weight loss on lipoprotein lipids in obese [body mass index (in kg/m2) > 27], postmenopausal women (n = 48) were determined. Subjects followed a euenergetic AHA Step 1 diet for 2 mo, followed by a weight-loss diet (deficit of 1.0-1.5 MJ/d) for 6 mo. The AHA diet lowered concentrations of total (7%), low-density-lipoprotein (LDL) (6%), and high-density-lipoprotein (HDL) (14%) cholesterol (P < 0.01). Weight loss (-5.6 +/- 0.7 kg; P < 0.01) increased plasma triacylglycerol concentrations (9%; P < 0.01) and increased HDL-cholesterol concentrations (8%; P < 0.01) compared with changes after the AHA diet, but there were no changes in total or LDL cholesterol. The combined AHA diet and weight-loss interventions lowered triacylglycerol (10%) and total (6%), LDL (6%), and HDL (7%) cholesterol. These changes correlated indirectly with the baseline concentration for each lipid. When the women were divided on the basis of initial LDL-cholesterol concentration, the AHA diet and weight-loss interventions reduced (P < 0.01) triacylglycerol (19%), total cholesterol (13%), and LDL cholesterol (14%) in the women with hypercholesterolemia but not in normocholesterolemic or midly hypercholesterolemic women. Thus, an AHA Step 1 diet and subsequent weight loss improve lipoprotein lipid profiles of obese, postmenopausal women with hypercholesterolemia. However, because it lowers HDL cholesterol, a low-fat diet without substantial weight loss may not be beneficial for improving lipoprotein lipid risk factors for coronary artery disease in obese, postmenopausal women with normal lipid profiles.

Energy requirements of middle-aged men are modifiable by physical activity.

BACKGROUND: Energy requirements for weight maintenance decrease with age. Often, this decline is not proportionately matched by reduced energy intake, resulting in weight gain. OBJECTIVE: We hypothesized that energy requirements for total daily weight maintenance in healthy, sedentary, middle-aged men would increase after regular aerobic exercise or aerobic exercise plus weight loss to levels comparable with those in middle-aged athletes. DESIGN: Weight-maintenance energy requirements were determined during weight stability (+/- 0.25 kg) in 14 lean, sedentary (LS) men; 18 obese, sedentary (OS) men; and 10 male athletes of comparable ages (x +/- SEM: 58 +/- 1 y). Studies were done at baseline and after 6 mo of aerobic exercise (LS men) or aerobic exercise plus weight loss (OS men) or 3 mo of deconditioning (athletes). RESULTS: The interventions raised maximal oxygen uptake (VO2max) by 15% in the LS men and by 13% in the OS men and decreased it by 14% in athletes (all P < 0.01), eliminating the differences among groups at baseline. Body fat was reduced significantly in LS and OS men; fat-free mass decreased in OS men. Average daily energy requirements increased by 8% in LS men and by 5% in OS men (both P < 0.01) to levels comparable with the baseline requirements of athletes and correlated with VO2max (r2 = 0.22, P < 0.0001) and fat-free mass (r2 = 0.05, P < 0.02) across the range of VO2max achieved by all subjects. CONCLUSIONS: Under free-living conditions, aerobic exercise eliminated the difference in weight-maintenance energy requirements between middle-aged sedentary and athletic men, suggesting that energy requirements of healthy, middle-aged men are modifiable by regular physical activity.

Effect of high carbohydrate feeding with dextrose or sucrose on adipose tissue lipoprotein lipase activity and plasma triglyceride levels in hemodialysis patients.

The acute effect of feeding high concentration carbohydrate meals containing equicaloric amounts of dextrose or sucrose on the activity of adipose tissue lipoprotein lipase and the concentration of plasma triglyceride was assessed in 11 hemodialysis patients. Dextrose feeding resulted in higher postprandial glucose levels and a greater insulin response than sucrose. The relationship between the postprandial change in the activity of adipose tissue lipoprotein lipase and the insulin response to feeding almost reached statistical significant (rs = 0.40, P = 0.08, n = 20), and the increase in the activity of the enzyme after dextrose feeding was greater than after sucrose (P less than 0.01). There was a significant decrease in plasma triglyceride levels after dextrose feeding (P less than 0.01), but no change was observed after the ingestion of sucrose. These results indicate that the inability of the administered sucrose to raise the plasma insulin concentration to the same level as isocaloric amounts of dextrose probably accounts for the smaller increase in the activity of adipose tissue lipoprotein lipase after sucrose. The failure of plasma triglyceride levels to fall after sucrose feeding suggests that the extent to which the activity of adipose tissue lipoprotein lipase increases postprandially may be important in the regulation of triglyceride metabolism in hemodialysis patients.

The metabolic and psychological effects of exercise training in hemodialysis patients.

The effect of exercise training on metabolic abnormalities and psychological function was assessed in seven hemodialysis patients. Their initial work capacity was low and improved after 8 months of training. Exercise was associated with a reduction in the dose of antihypertensive medications in four patients and a decrease in phosphate binder therapy in three patients. There was also a rise in hematocrit levels (% delta = 34 +/- 20%, P less than 0.03) and the hemoglobin concentration (% delta = 37 +/- 23%, P less than 0.05) of five males. Plasma glucose levels fell (-5 +/- 2%, P less than 0.05, n = 5) and the glucose disappearance rate improved (20 +/- 7%, P less than 0.02), while hyperinsulinism decreased (-36 +/- 20%, P less than 0.02, n = 5) during training. There was no change in body weight or diet. Exercise lowered plasma triglyceride levels (-41 +/- 28%, P less than 0.02, n = 6) and raised the high-density lipoprotein cholesterol concentration (20 +/- 21%, P less than 0.05, n = 6). Psychological testing (n = 4) demonstrated that exercise training was associated with an improvement in depression, hostility, anxiety, social interaction, and outlook for the future. These results suggest that exercise can improve some of metabolic abnormalities and psychological dysfunction which exists in some dialysis patients.

Soy fiber improves lipid and carbohydrate metabolism in primary hyperlipidemic subjects.

This study was designed to evaluate the effects of soy fiber, a natural source of dietary fiber that consists of both cellulosic and noncellulosic dietary fiber, on human plasma lipoprotein lipids and glucose tolerance in patients with primary hyperlipidemia. Supplementing 25 g of soy fiber per day provided a significant additional reduction of plasma total-cholesterol by 13 mg/dl (P less than 0.04) and LDL cholesterol by 12 mg/dl (P less than 0.05) beyond that previously achieved by treatment with an NIH Type II-A low-fat, low-cholesterol diet for 12 weeks in Type II-A hypercholesterolemic patients. There were no effects on HDL cholesterol or apoprotein A-I and A-II levels. The hypocholesterolemic effect was greater than in the hyperlipidemic patients with impaired glucose tolerance. Soy fiber supplementation also significantly reduced insulin responses to oral glucose challenge by 20% in Type II-A hypercholesterolemic and by 16.5% in Type IV hypertriglyceridemic patients. Results from this study suggest that supplementing the diet with soy fiber may be beneficial in dietary management of hyperlipidemia in patients with hypercholesterolemia and particularly in hyperlipidemic patients with hyperinsulinemia and impaired glucose tolerance.

Comparison of hypocholesterolemic activity for cyclic analogs of clofibrate in normolipemic rats.

Chronic administration of ethyl 2-methyl-2(4-chlorophenoxy)-propionate [clofibrate, CPIB], ethyl 6-cyclohexylchroman-2carboxylate, and ethyl 6-phenylchroman-2-carboxylate to normolipemic rats, in vivo, reduced serum cholesterol levels and inhibitid the activiry of hepatic 3-hydroxy-3methyl-glutaryl Coenzyme A. Only clofibrate was found to lower liver cholesterol content after pretreatment for 4 or 18 days. The cyclic analogs, ethyl 6-cholorochromone-2-carboxylate and 9-chloro-2,3-dihydro-5H-1,4-dioxepino [6,5-b] benzofuran were inaffective as cholesterol lowering agents in normolipemic rats. These findings indicate that appropriate modification of clofibrate can lead to the development of compounds which are selective and equally effective to clofibrate as potential hypocholesterolemic agents. Results obtained in these studies are also discussed in terms of the known structural requirements of biological activity for this series of cyclic analogs in the Triton WR-1339 hyperlipemic rat model and modes of action of the parent compound.