Fasting Plasma Norepinephrine Research Articles

Individual Thermogenic Responses to Mild Cold and Overfeeding Are Closely Related

Adaptive thermogenesis is defined as the increase in energy expenditure in response to overfeeding or cold. Large interindividual differences in adaptive thermogenesis have been described. Because there are indications for a common underlying mechanism, we studied in humans whether the increase in thermogenesis during short-term overfeeding (3 d) is related to mild cold-induced thermogenesis. Thirteen lean male subjects have been exposed to three experimental conditions in respiration chambers: baseline (36 h in energy balance at thermoneutrality, 22 C), overfeeding (84 h at 160% of energy balance, 22 C), and mild cold (84 h in energy balance, 16 C). During the interventions, total daily energy expenditure (TDEE), physical activity, skin temperatures, and core temperature were measured. After each condition, fasting plasma norepinephrine concentration was measured. Overfeeding caused significant increases in TDEE (0.77 MJ/d, P < 0.001). During cold exposure TDEE increased significantly (0.59 MJ/d, P < 0.005), whereas physical activity decreased. The changes in TDEE during both overfeeding and mild cold exposure showed considerable interindividual variation (respectively, -0.11 to 1.61 MJ/d and -0.19 to 1.58 MJ/d). The individual changes in energy expenditure during mild cold exposure and overfeeding were highly correlated (P < 0.005). Fasting norepinephrine plasma concentrations correlated significantly to energy expenditure in both situations (P < 0.05). These results suggest that both overfeeding-induced and mild cold-induced adaptive thermogenesis share common regulating mechanisms. This indicates that cold exposure could be used as a biomarker for the individual thermogenic response to excess energy intake.

Effect of moderate cold exposure on 24-h energy expenditure: similar response in postobese and nonobese women.

Twenty-four-hour energy expenditure (EE) and substrate oxidation rates were measured two times in eight postobese women and eight matched controls. On one occasion the subjects were exposed to a room temperature of 16 degrees C, on the other to 24 degrees C. Cold exposure elicited a 2% increment in 24-h EE (P < 0.05), with similar response in the two groups. The slight increase in EE was entirely covered by an enhanced carbohydrate oxidation rate. Fasting plasma norepinephrine (NE) increased from 0.74 +/- 0.08 to 1.29 +/- 0.21 nmol/l under cold exposure (P < 0.05), with no group difference. The cold-induced increase in 24-h EE was positively correlated to the increase in NE concentration (r2 = 0.41, P = 0.01). Sleeping EE was found to be 5% lower in the postobese women than in the controls (P = 0.04). The postobese group also had higher 24-h nonprotein respiratory quotient than the control group (P = 0.04), which was due to a 26% lower lipid-to-carbohydrate oxidation ratio. The study demonstrates that the thermogenic response to cold is normal in women susceptible to obesity, but it supports previous reports of a slightly lower basal EE and lower lipid-to-carbohydrate oxidation ratio in postobese subjects.

Serum uric acid and plasma norepinephrine concentrations predict subsequent weight gain and blood pressure elevation.

It has been reported that hypertension and obesity often coexist with hyperuricemia. To clarify the relations between serum uric acid, plasma norepinephrine, and insulin or leptin levels in subjects with weight gain-induced blood pressure elevation, we conducted the present longitudinal study. In 433 young, nonobese, normotensive men, body mass index, blood pressure, and levels of serum uric acid, fasting plasma norepinephrine, insulin, and leptin were measured every year for 5 years. Subjects were stratified by significant weight gain and/or blood pressure elevation (>10% in body mass index or mean blood pressure) for 5 years. At entry, blood pressure, uric acid, and norepinephrine values in subjects with blood pressure elevation were greater than in those without it, although body mass index, insulin, and leptin were similar. At entry, body mass index, blood pressure, uric acid, and norepinephrine in subjects with weight gain were greater than in those without weight gain. The increases in body mass index, mean blood pressure, uric acid, norepinephrine, insulin, and leptin for 5 years were greater in subjects with blood pressure elevation and/or weight gain than in subjects without, and those increases were greatest in subjects with weight gain whose blood pressure was elevated. By multiple regression analysis, basal mean blood pressure, norepinephrine, and uric acid were significant determinant factors of changes in mean blood pressure over 5 years, and basal body mass index, norepinephrine, and uric acid were significant determinant factors of changes in body mass index. These results demonstrate that serum uric acid and plasma norepinephrine concentrations predict subsequent weight gain and blood pressure elevation.

Differences in Mechanisms Between Weight Reduction Sensitive and Insensitive Blood Pressure Reduction in Obese Subjects

P180 This study was conducted to clarify the differences in mechanisms between weight reduction (WR) sensitive and insensitive BP reduction, and to evaluate the contribution of family history of obesity (FH) to WR-induced BP reduction. In 61 obese hypertensive men (HT, 28.1±0.9 kg/m2, 35±3 years, 171±6/106±5 mmHg) and 52 obese normotensive men (NT, 27.9±0.6 kg/m2, 34±4 years, 131±5/83±4 mmHg), BMI, BP, fasting plasma norepinephrine (NE), angiotensin II (Ang II), PRA, leptin, insulin were measured every 2 week for 24 weeks with weight loss program (low caloric diet 1000kcal, 7gNaCl + excercise≥1 hr/day). WR and WR sensitive BP reduction were defined as >10% reduction in BMI or mean BP at week 12. 64% of HT and 63% of NT succeeded in WR, and 59% of HT with WR (sensitive vs insensitive P 27.0 kg/m2), prevalence of FH+ was higher in 86% of HT and 95% of NT who failed in WR, and higher in 94% of HT and 80% of NT with WR insensitive BP reduction. Only the subjects who succeeded in WR were analyzed in this study. At entry, BP, NE, Ang II, PRA and insulin were higher in HT than in NT, although BMI and leptin were similar. However, the parameters at entry were similar between WR sensitive and insensitive BP reduction in each NT and HT. The decrements (Δ) in BP, NE, Ang II, leptin,insulin were significantly greater in subjects with WR sensitive BP reduction than subjects with WR insensitive BP reduction regardless of BP status during the study, although ΔBMI was similar. Significant decreases in the parameters were noted in earlier period in subjects with WR sensitive BP reduction than in subjects with insensitive BP reduction, and in NT than in HT. In the 4 study groups regardless of BP status or WR induced BP reduction, the decrease in NE preceded BP decline, and the decreases in Ang II, insulin, leptin & PRA followed BP decline with WR. These results suggest that a family history of obesity appears to contribute closely to resistance in weight loss and also to WR insensitive BP reduction. Suppression on sympathetic overactivity is a major mechanism in WR induced BP reduction.

Differences in Mechanisms Between Weight Reduction Sensitive and Insensitive Blood Pressure Reduction in Obese Subjects

P180 This study was conducted to clarify the differences in mechanisms between weight reduction (WR) sensitive and insensitive BP reduction, and to evaluate the contribution of family history of obesity (FH) to WR-induced BP reduction. In 61 obese hypertensive men (HT, 28.1±0.9 kg/m2, 35±3 years, 171±6/106±5 mmHg) and 52 obese normotensive men (NT, 27.9±0.6 kg/m2, 34±4 years, 131±5/83±4 mmHg), BMI, BP, fasting plasma norepinephrine (NE), angiotensin II (Ang II), PRA, leptin, insulin were measured every 2 week for 24 weeks with weight loss program (low caloric diet 1000kcal, 7gNaCl + excercise≥1 hr/day). WR and WR sensitive BP reduction were defined as &gt;10% reduction in BMI or mean BP at week 12. 64% of HT and 63% of NT succeeded in WR, and 59% of HT with WR (sensitive vs insensitive P&lt;.05) and 70% of NT with WR (P&lt;.01) were sensitive in BP reduction. When FH+ was defined as at least one parent was obese (BMI&gt;27.0 kg/m2), prevalence of FH+ was higher in 86% of HT and 95% of NT who failed in WR, and higher in 94% of HT and 80% of NT with WR insensitive BP reduction. Only the subjects who succeeded in WR were analyzed in this study. At entry, BP, NE, Ang II, PRA and insulin were higher in HT than in NT, although BMI and leptin were similar. However, the parameters at entry were similar between WR sensitive and insensitive BP reduction in each NT and HT. The decrements (Δ) in BP, NE, Ang II, leptin,insulin were significantly greater in subjects with WR sensitive BP reduction than subjects with WR insensitive BP reduction regardless of BP status during the study, although ΔBMI was similar. Significant decreases in the parameters were noted in earlier period in subjects with WR sensitive BP reduction than in subjects with insensitive BP reduction, and in NT than in HT. In the 4 study groups regardless of BP status or WR induced BP reduction, the decrease in NE preceded BP decline, and the decreases in Ang II, insulin, leptin &amp; PRA followed BP decline with WR. These results suggest that a family history of obesity appears to contribute closely to resistance in weight loss and also to WR insensitive BP reduction. Suppression on sympathetic overactivity is a major mechanism in WR induced BP reduction.

Weight gain-induced blood pressure elevation.

This study was conducted to evaluate the mechanisms in weight gain-induced blood pressure (BP) elevation focusing, in particular, on the contributions of sympathetic nervous system activity, fasting plasma insulin, and leptin to BP levels. The study design was longitudinal with a cohort of 1897 men. BP, pulse rate, body mass index (BMI), fasting plasma norepinephrine (NE), insulin, and leptin were measured at 6 and 12 months in those 172 lean normotensive, 79 obese normotensive, 64 lean untreated hypertensive, and 38 obese untreated hypertensive men whose BMI increased >10% during the first 6 months. At entry, levels of BP, pulse rate, plasma NE, insulin, and leptin in obese subjects, regardless of BP status, were significantly greater than those in lean subjects. The levels of plasma NE, insulin, and leptin increased with weight gain in the 4 study groups. In the subjects with BP elevation, the increase in pulse rate and plasma NE was significantly greater than that in the subjects without BP elevation at both 6 and 12 months for each of the 4 study groups, although the increase in BMI was similar between the subjects with and without BP elevation. In obese but not lean subjects, whether normotensive or hypertensive, the increases in plasma insulin and plasma leptin with weight gain were greater in the subjects with accompanying BP elevation compared with the subjects without BP elevation. On the other hand, at 6 months in lean subjects, the increase in plasma insulin with weight gain in the subjects with BP elevation was actually lower than that in the subjects without BP elevation. These results suggest that weight gain-induced sympathetic overactivity is more tightly linked to weight gain-induced BP elevation than the changes in plasma insulin and leptin that also accompany weight gain. It is probable that sympathetic nervous activation with weight gain is a major mechanism of blood pressure elevation. Hyperinsulinemia and hyperleptinemia may be ancillary factors that contribute to sympathetic nervous stimulation with weight gain.

Effects of glucose ingestion on cardiac autonomic nervous system in healthy centenarians: differences with aged subjects.

Spectral analysis of heart rate variability (HRV) investigates the cardiac autonomic nervous system (ANS) activity. In particular, low frequency/high frequency (LF/HF) is considered an index of cardiac sympatho-vagal balance and is stimulated by glucose ingestion in healthy subjects. No studies have evaluated the effect of glucose ingestion on cardiac ANS in centenarians. In 30 healthy centenarians (HC) and 25 aged subjects (AS) power spectral analysis of HRV was investigated during an oral glucose ingestion. Glucose ingestion rose LF/HF ratio in both groups studied. Such stimulatory effects were restrained to the first 60 min of the study. Independent of age, gender, body mass index (BMI) and fasting plasma norepinephrine and FT3 concentrations, HC had basal total power (1318 +/- 546 vs. 1918 +/- 818 msec2, P < 0.01), lower low frequency (LF) (33 +/- 21 vs. 50 +/- 11 n.u., P < 0. 03), and higher high frequency (HF) (74 +/- 18 vs. 43 +/- 15 n.u., P < 0.05) than AS. Consequently, LF/HF ratio (0.43 +/- 0.07 vs. 0.91 +/- 0.05, P < 0.02) was also lower in HC than in AS. In AS, but not in HC, the baseline LF/HF ratio correlated significantly with BMI (r = 0.48, P < 0.01), waist-hip-ratio (WHR) (r = 0.45, P < 0.02), fasting plasma insulin (r = 0.49, P < 0.01) and norepinephrine (r = 0.57, P < 0.02) concentration. Glucose ingestion was associated with a significant rise in LF/HF ratio in both groups studied but per cent changes in glucose mediated stimulation of LF/HF was lower in HC than in AS. In a control study, water administration did not affect power spectral parameters of HRV. Our study demonstrates that basal- and glucose-stimulated LF/HF, an indirect index of cardiac sympatho-vagal balance, are lower in HC than in AS.

Sympathetic activity and body mass index contribute to blood pressure levels.

The purpose of this study was to clarify the relationships between obesity (BMI) and BP levels, leptin levels, sympathetic activity, and insulin sensitivity in a Japanese male population. In 912 young, non-diabetic, Japanese men with a wide range of BMI (16.5-33.6 kg/m2), blood pressure (BP), fasting plasma norepinephrine (NE), insulin and leptin levels were measured after an overnight fast. The cohort consisted of 603 normotensive and 309 hypertensive subjects. The study was carried out using a cross-sectional design. When the subjects were subdivided by tertile in relation to BMI, the 101 subjects in the heaviest group (BMI > 27.9 kg/m2) had a significantly higher systolic BP (p< 0.05) and pulse rate (p< 0.05) as well as higher NE (p< 0.01), insulin (p< 0.01), and leptin (p< 0.01) levels than 86 subjects in the leanest group (BMI < 22.2 kg/m2). In the whole cohort, BMI correlated with mean BP (p< 0.01), plasma NE (p< 0.05), insulin (p< 0.001) and leptin (p< 0.001). The mean BP correlated with BMI (p< 0.001), plasma NE (p< 0.01), insulin (p< 0.01) and leptin (p< 0.05). Plasma leptin levels correlated with fasting plasma insulin levels (p < 0.05), but not with plasma NE levels (NS). As analyzed by multiple regression analysis, only plasma NE (p< 0.05) and BMI (p< 0.001), but not plasma insulin levels, were significant, independent predictors of BP levels (r2=0.125, F= 10.51, p=0.0001). These results suggest that obesity (BMI) and heightened sympathetic nervous system activity contribute to BP elevation (hypertension).

Prognostic importance of insulin-mediated glucose uptake in aged patients with congestive heart failure secondary to mitral and/or aortic valve disease

Previous studies have demonstrated that insulin resistance is a common feature of congestive heart failure (CHF), but the clinical significance of such insulin resistance is still debated. We tested the hypothesis that insulin-mediated glucose uptake (IMGU) is a prognostic factor in CHF in aged patients. For this purpose 174 aged patients with CHF participated in a cross-sectional and a longitudinal study of 24 months’ duration. In this latter study survival analysis was calculated comparing subjects at the first and second tertile of IMGU with those at third tertile. All subjects underwent anthropometric (body mass index, waist/hip ratio), cardiovascular (arterial blood pressure, 24-hour Holter monitoring, peak VO 2, left ventricular ejection fraction, echocardiography), and metabolic (determination of fasting plasma glucose, insulin, catecholamine, free fatty acids, tumor necrosis factor-α concentrations, and assessment of IMGU by euglycemic hyperinsulinemic glucose clamp) investigations. In the cross-sectional study, IMGU correlated with age (r = −0.33, p <0.001), body mass index (r = −0.46 p <0.001), ventricular premature complexes (r = −0.78, p <0.001), left ventricular ejection fraction (r = −0.15, p <0.05), fasting plasma norepinephrine (r = −0.75, p <0.001), tumor necrosis factor-α (r = −0.45, p <0.001), free fatty acids (r = −0.54, p <0.001), and peak VO 2 (r = 0.67, p <0.001). In the longitudinal study patients at the first and second tertile of IMGU had a lower probability of survival than patients at the third tertile (p <0.03). Cox regression analysis showed IMGU to be a prognostic factor independent of fasting plasma norepinephrine, tumor necrosis factor-α, free fatty acid concentration, New York Heart Association class, peak VO 2, and left ventricle ejection fraction (relative risk 1.1, 95% confidence intervals 1.0 to 2.1). In conclusion, our study demonstrates that insulin resistance is a common feature of CHF most likely due to elevated plasma norepinephrine and tumor necrosis factor-α concentrations, and that IMGU is an independent prognostic factor in CHF.

Free Fatty Acid Kinetics and Oxidation in Congestive Heart Failure

To characterize fuel utilization of patients with congestive heart failure (CHF), we measured serum free fatty acid (FFA), counterregulatory hormone concentrations, whole body substrate oxidation rates (indirect calorimetry), and the turnover and oxidation rates of FFA ([1- 14C]-palmitate infusion) in 7 patients with CHF and in 7 cardiac patients without CHF after an overnight fast. Plasma glucose and serum insulin concentrations were comparable, whereas serum FFA, blood ketone body, and fasting blood lactate (p <0.05 for all) concentrations were significantly increased in patients with CHF compared to those without CHF. Fasting plasma norepinephrine (p <0.05), serum cortisol (p <0.01), and growth hormone (p <0.01) concentrations were also higher in patients with CHF than in those without CHF. Rates of energy expenditure at rest (62 ± 2 vs 56 ± 1 J · kg −1 · min −1, p <0.05), FFA turnover (6.5 ± 0.5 vs 5.0 ± 0.4 μmol · kg −1 · min −1, p <0.05), and oxidation (2.0 ± 0.2 vs 1.5 ± 0.1 μmol · kg −1 · min −1, p <0.05) were significantly higher in patients with CHF than in control subjects. In univariate analysis, the left ventricular ejection fraction was inversely correlated and the plasma norepinephrine concentration positively correlated with both energy expenditure at rest, FFA turnover, and the FFA oxidation rate. In multivariate analysis, the plasma norepinephrine concentration was the most significant predictor of increased FFA oxidation rate. We conclude that release of FFAs to the circulation and their subsequent oxidation are increased in patients with severe CHF after an overnight fast. These changes might reflect stress hormone-induced lipolysis and accompanying stimulation of serum FFA oxidation via mass action.

Abnormal epinephrine release in young adults with high personal and high parental blood pressures.

Increased activity of the sympathetic nervous system has been proposed as a cause of high blood pressure (BP) and may be related to diet and body weight. To determine the role of these factors in predisposition to high BP, we studied 100 young adults with high or low BP from families in which both parents had either high or low BP. Plasma catecholamine, glucose, and insulin levels were measured before and after an oral glucose load. There was a significant correlation between fasting plasma norepinephrine and mean arterial pressure (P=.001). Subjects with high BP, irrespective of parental BP, were heavier (P=.003) and fatter (P=.002) and had a greater rise in plasma insulin (P=.003) following glucose than those with low BP. Offspring with high BP whose parents also had high BP showed an unexpected rise in plasma epinephrine (P=.004) following glucose. This adrenal medullary response was not the result of high parental or high personal BP alone as it was not seen in offspring with low BP whose parents had high BP or in offspring with high BP whose parents had low BP. Irrespective of family history, high BP is associated with increased body weight and hyperinsulinemia and reflects personal environment and behavior. However, abnormal epinephrine release is characteristic of the combination of genetic, environmental, and behavioral factors that is associated with high personal BP and a familial predisposition to high BP.

Effect of moderate cold exposure on 24-h energy expenditure: similar response in postobese and nonobese women

Twenty-four-hour energy expenditure (EE) and substrate oxidation rates were measured two times in eight postobese women and eight matched controls. On one occasion the subjects were exposed to a room temperature of 16 degrees C, on the other to 24 degrees C. Cold exposure elicited a 2% increment in 24-h EE (P &lt; 0.05), with similar response in the two groups. The slight increase in EE was entirely covered by an enhanced carbohydrate oxidation rate. Fasting plasma norepinephrine (NE) increased from 0.74 +/- 0.08 to 1.29 +/- 0.21 nmol/l under cold exposure (P &lt; 0.05), with no group difference. The cold-induced increase in 24-h EE was positively correlated to the increase in NE concentration (r2 = 0.41, P = 0.01). Sleeping EE was found to be 5% lower in the postobese women than in the controls (P = 0.04). The postobese group also had higher 24-h nonprotein respiratory quotient than the control group (P = 0.04), which was due to a 26% lower lipid-to-carbohydrate oxidation ratio. The study demonstrates that the thermogenic response to cold is normal in women susceptible to obesity, but it supports previous reports of a slightly lower basal EE and lower lipid-to-carbohydrate oxidation ratio in postobese subjects.

Protein-induced changes in energy expenditure in young and old individuals

Resting energy expenditure (EE) has recently been shown to be reduced in elderly human subjects even after adjustment for body size and composition. The present study extended this examination of EE in relation to age by comparing the thermic effect of a protein meal in young men (YM 20-26 yr, n = 9), old men (OM 70-89 yr, n = 9), and old women (OW 67-75 yr, n = 6). EE was measured before and from 1 to 6 h after presentation of 60 g protein and of a control noncaloric meal on separate occasions. Despite substantial differences in body size and composition, the protein-induced increment in EE was similar in all groups [maximum increase: YM 0.21 +/- 0.05, OM 0.17 +/- 0.12, and OW 0.17 +/- 0.04 (SE) kcal/min]. Although fasting plasma norepinephrine (NE) levels differed among all three groups (YM less than OM less than OW), NE concentrations were not affected by protein ingestion. Because protein administration acutely promotes synthesis of dopamine (DA) and serotonin (5-HT), which are both capable of stimulating EE, blockade of extraneuronal synthesis of DA and 5-HT with carbidopa, a competitive inhibitor of aromatic-L-amino acid decarboxylase, failed to suppress (and actually increased) postprandial EE. These data demonstrate that not all mechanisms responsible for EE decline with age and that protein-induced changes in EE are more a function of the oral load itself than of the size, age, or antecedent diet of the individual ingesting the protein.