Physiological evidence for the involvement of peptide YY in the regulation of energy homeostasis in humans

Objective: To explore the potential role of the endogenous peptide YY (PYY) in the long‐term regulation of body weight and energy homeostasis. Research Methods and Procedures: Fasting and postprandial plasma PYY concentrations were measured after an overnight fast and 30 to 180 minutes after a standardized meal in 29 (21 men/8 women) non‐diabetic subjects, 16 of whom had a follow‐up visit 10.8 ± 1.4 months later. Ratings of hunger and satiety were collected using visual analog scales. Resting metabolic rate (RMR) (15‐hour RMR) and respiratory quotient (RQ) were assessed using a respiratory chamber. Results: Fasting PYY concentrations were negatively correlated with various markers of adiposity and negatively associated with 15‐hour RMR (r = ?0.46, p = 0.01). Postprandial changes in PYY (area under the curve) were positively associated with postprandial changes in ratings of satiety (r = 0.47, p = 0.01). The maximal PYY concentrations achieved after the meal (peak PYY) were negatively associated with 24‐hour RQ (r = ?0.41, p = 0.03). Prospectively, the peak PYY concentrations were negatively associated with changes in body weight (r = ?0.58, p = 0.01). Discussion: Our data indicate that the endogenous PYY may be involved in the long‐term regulation of body weight. It seems that this long‐term effect was not exclusively driven by the modulation of food intake but also by the control of energy expenditure and lipid metabolism.     

Impact of meal timing and frequency on the twenty-four-hour leptin rhythm

OBJECTIVE: To study the influence of changes in meal timing and frequency on the diurnal rhythm of leptin and on the 24-hour profile of insulin and glucose. PATIENTS AND METHODS: Five obese women were studied twice during a weight-maintaining diet in either 3 daily or 8 day and night equal portions. Blood was sampled for 24-hour profiles of leptin and insulin. RESULTS: During the 8-meal intervention, the 24-hour rhythm of leptin changed significantly: the amplitude decreased (p = 0.0089) and the acrophase was delayed by 168 min (p = 0.021). Also, 8 small insulin secretion peaks occurred instead of the 3 postprandial high insulin peaks. CONCLUSION: The dispersion of food intake over 24 h affects the diurnal leptin rhythm. These changes could not be attributed to changes in circadian timing or energy balance. Instead, changes in daily insulin secretion profiles might play a role.     

Low energy availability, not exercise stress, suppresses the diurnal rhythm of leptin in healthy young women

Because the effect of exercise on leptin was not established, we controlled energy intake (I) and exercise energy expenditure (E) to distinguish the independent effects of energy availability (A = I - E) and exercise stress (everything associated with exercise except its energy cost) on the diurnal leptin rhythm in healthy young women. In random order, we set A = 45 and 10 kcal. kg lean body mass(-1) (LBM) x day(-1) for 4 days during the early follicular phase of separate menstrual cycles in sedentary (S, n = 7) and exercising (X, n = 9: E = 30 kcal x kg LBM(-1) x day(-1)) women. Low energy availability suppressed the 24-h mean (P < 10(-6)) and amplitude (P < 10(-5)), whereas exercise stress did not (both P > 0.2). Suppressions of the 24-h mean (-72 +/- 3 vs. -53 +/- 3%, P < 0.001) and amplitude (-85 +/- 3 vs. -58 +/- 6%, P < 0.001) were more extreme in S vs. X than previously reported effects on luteinizing hormone pulsatility and carbohydrate availability. Thus the diurnal rhythm of leptin depends on energy, or carbohydrate, availability, not intake, and exercise has no suppressive effect on the diurnal rhythm of leptin beyond the impact of its energy cost on energy availability.     

Direct evidence for tonic sympathetic support of resting metabolic rate in healthy adult humans

The sympathetic nervous system (SNS) plays an important role in the regulation of energy expenditure. However, whether tonic SNS activity contributes to resting metabolic rate (RMR) in healthy adult humans is controversial, with the majority of studies showing no effect. We hypothesized that an intravenous propranolol infusion designed to achieve complete beta-adrenergic blockade would result in a significant acute decrease in RMR in healthy adults. RMR (ventilated hood, indirect calorimetry) was measured in 29 healthy adults (15 males, 14 females) before and during complete beta-adrenergic blockade documented by plasma propranolol concentrations > or =100 ng/ml, lack of heart rate response to isoproterenol, and a plateau in RMR with increased doses of propranolol. Propranolol infusion evoked an acute decrease in RMR (-71 +/- 11 kcal/day; -5 +/- 0.7%, P < 0.0001), whereas RMR was unchanged from baseline levels during a saline control infusion (P > 0.05). The response to propranolol differed from the response to saline control (P < 0.01). The absolute and percent decreases in RMR with propranolol were modestly related to baseline plasma concentration of norepinephrine (r = 0.38, P = 0.05; r = 0.44, P = 0.02, respectively). These findings provide direct evidence for the concept of tonic sympathetic beta-adrenergic support of RMR in healthy nonobese adults.     

Age-related decline in RMR in physically active men: relation to exercise volume and energy intake

We tested the hypothesis that resting metabolic rate (RMR) declines with age in physically active men (endurance exercise > or =3 times/wk) and that this decline is related to weekly exercise volume (h/wk) and/or daily energy intake. Accordingly, we studied 137 healthy adult men who had been weight stable for > or =6 mo: 32 young [26 +/- 1 (SE) yr] and 34 older (62 +/- 1 yr) sedentary males (internal controls); and 39 young (27 +/- 1 yr) and 32 older (63 +/- 2 yr) physically active males (regular endurance exercise). RMR was measured by indirect calorimetry (ventilated hood system) after an overnight fast and approximately 24 h after exercise. Because RMR is related to fat-free mass (FFM; r = 0.76, P < 0.001, current study), FFM was covaried to adjust RMR (RMR(adj)). RMR(adj) was lower with age in both the sedentary (72.0 +/- 2.0 vs. 64.0 +/- 1.3 kcal/h, P < 0.01) and the physically active (76.6 +/- 1.1 vs. 67.9 +/- 1.2 kcal/h, P < 0.01) males. In the physically active men, RMR(adj) was related to both exercise volume (no. of h/wk, regardless of intensity; r = 0.56, P < 0.001) and estimated energy intake (r = 0.58, P < 0.001). Consistent with these relations, RMR(adj) was not significantly different in subgroups of young and older physically active men matched either for exercise volume (h/wk; n = 11 each) or estimated energy intake (kcal/day; n = 6 each). These results indicate that 1) RMR, per unit FFM, declines with age in highly physically active men; and 2) this decline is related to age-associated reductions in exercise volume and energy intake and does not occur in men who maintain exercise volume and/or energy intake at a level similar to that of young physically active men.     

Resting metabolic rate and thermic effects of a sucrose-sweetened soft drink during the menstrual cycle in young Chinese women.

The resting metabolic rate (RMR) and thermic effects (TEF) of a sucrose-sweetened soft drink in a group (n = 19) of ovulating young Chinese women were determined by indirect calorimetry in the midfollicular and midluteal phases of the menstrual cycle. Urinary luteinizing hormone surge was used to confirm ovulation. The RMR was measured twice in each phase and found to be similar (F(1,18) = 0.863) across the follicular (5018 kJ/24 h) and the luteal (5098 kJ/24 h) phases. Within each phase and on separate days, subjects were given water (280 mL) or sucrose-sweetened soft drink (539 kJ). Soft drink, but not water, consumption increased energy expenditure over a period of 45 min. Compared with the follicular phase, a small but significant increase in TEF (kJ/45 min) was observed in the luteal phase (t = 2.434, p < 0.05). Energy expenditure after drinking the soft drink, however, was similar in the two phases. RMR was positively correlated with TEF (r = 0.613, p < 0.01) and net TEF (r = 0.648, p < 0.005) in the luteal but not the follicular phase. In ovulating women, the thermic effect of sucrose is influenced by the phase of the menstrual cycle.     

Changes in 24-h substrate oxidation in older and younger men in response to exercise.

The purpose of this study was to compare 24-h substrate oxidation in older (OM; 60-75 yr, n = 7) and younger (YM; 20-30 yr, n = 7) men studied on sedentary day (Con) and on a day with exercise (Ex; net energy expenditure = 300 kcal). Plasma glucose and free fatty acids were also measured at several time points during the 24-h measurement. Weight was not different in OM and YM (means +/- SD; 84.8 +/- 16.9 vs. 81.4 +/- 10.4 kg, respectively), although percent body fat was slightly higher in OM (25.9 +/- 3.5 vs. 21.9 +/- 9.7%; P = 0.17).Values of 24-h energy expenditure did not differ in OM and YM on the Con (means +/- SE; 2,449 +/- 162 vs. 2,484 +/- 104 kcal/day, respectively) or Ex (2,902 +/- 154 vs. 2,978 +/- 122 kcal/day) days. Under both conditions, 24-h respiratory quotient was significantly lower and fat oxidation significantly higher in OM. Glucose concentrations were not different at any time point, but plasma free fatty acid concentrations were higher in OM, particularly following meals. Thus, under these controlled conditions, 24-h fat oxidation was not reduced and was in fact greater in OM. We speculate that differences in the availability of circulating free fatty acids in the postprandial state contributed to the observed differences in 24-h fat oxidation in OM and YM.     

Twenty-four hour secretory pattern of thyroid-stimulating hormone in hyperprolactinemic women with pituitary microadenoma

In order to determine whether endogenous dopaminergic tone has any role in the diurnal variation in TSH secretion, the 24-h secretory pattern of TSH and the TSH response to a dopamine antagonist, metoclopramide (MCP), were evaluated in normal women (n = 4) and in hyperprolactinemic-amenorrheic women with pituitary microadenoma (n = 6). TSH concentrations expressed as percent deviation from the 24-h mean significantly differed with respect to time of day in normal women and hyperprolactinemic women. They were significantly higher during the night (2000-0700 h) than during the daytime (0800-1900 h). Whereas MCP administration induced no significant changes in serum TSH levels in normal women, it significantly increased serum TSH levels in hyperprolactinemic women. Thus, the diurnal variation in TSH secretion was demonstrated in hyperprolactinemic women with pituitary microadenoma in the face of an increased dopaminergic inhibition of TSH secretion. The present study did not provide evidence that the diurnal pattern of TSH secretion is related to the endogenous dopaminergic tone.     

Pulsatile and nocturnal growth hormone secretions in men do not require periodic declines of somatostatin

Using a continuous subcutaneous octreotide infusion to create constant supraphysiological somatostatinergic tone, we have previously shown that growth hormone (GH) pulse generation in women is independent of endogenous somatostatin (SRIH) declines. Generalization of these results to men is problematic, because GH regulation is sexually dimorphic. We have therefore studied nine healthy young men (age 26 +/- 6 yr, body mass index 23.3 +/- 1.2 kg/m2) during normal saline and octreotide infusion (8.4 microg/h) that provided stable plasma octreotide levels (764.5 +/- 11.6 pg/ml). GH was measured in blood samples obtained every 10 min for 24 h. Octreotide suppressed 24-h mean GH by 52 +/- 13% (P = 0.016), GH pulse amplitude by 47 +/- 12% (P = 0.012), and trough GH by 39 +/- 12% (P = 0.030), whereas GH pulse frequency and the diurnal rhythm of GH secretion remained essentially unchanged. The response of GH to GH-releasing hormone (GHRH) was suppressed by 38 +/- 15% (P = 0.012), but the GH response to GH-releasing peptide-2 was unaffected. We conclude that, in men as in women, declines in hypothalamic SRIH secretion are not required for pulse generation and are not the cause of the nocturnal augmentation of GH secretion. We propose that GH pulses are driven primarily by GHRH, whereas ghrelin might be responsible for the diurnal rhythm of GH.     

Differences in daily energy expenditure in lean and obese women: the role of posture allocation

Objective: A low resting metabolic rate (RMR) is considered a risk factor for weight gain and obesity; however, due to the greater fat‐free mass (FFM) found in obesity, detecting an impairment in RMR is difficult. The purposes of this study were to determine the RMR in lean and obese women controlling for FFM and investigate activity energy expenditure (AEE) and daily activity patterns in the two groups. Methods and Procedures: Twenty healthy, non‐smoking, pre‐menopausal women (10 lean and 10 obese) participated in this 14‐day observational study on free‐living energy balance. RMR was measured by indirect calorimetry; AEE and total energy expenditure (TEE) were calculated using doubly labeled water (DLW), and activity patterns were investigated using monitors. Body composition including FFM and fat mass (FM) was measured by dual energy X‐ray absorptiometry (DXA). Results: RMR was similar in the obese vs. lean women (1601 ± 109 vs. 1505 ± 109 kcal/day, respectively, P = 0.12, adjusting for FFM and FM). Obese women sat 2.5 h more each day (12.7 ± 3.2 h vs. 10.1 ± 2.0 h, P < 0.05), stood 2 h less (2.7 ± 1.0 h vs. 4.7 ± 2.2 h, P = 0.02) and spent half as much time in activity than lean women (2.6 ± 1.5 h vs. 5.4 ± 1.9 h, P = 0.002). Discussion: RMR was not lower in the obese women; however, they were more sedentary and expended less energy in activity than the lean women. If the obese women adopted the activity patterns of the lean women, including a modification of posture allocation, an additional 300 kcal could be expended every day.     

Plasma concentrations of testosterone and LH in the male dog

Blood samples were withdrawn every 20 min from 3 conscious intact and 2 castrated mature males during non-consecutive periods of 12 h during the light and dark phases of the lighting schedule (intact dogs) and of 11 h during the light period (castrated dogs). In the intact dogs testosterone concentrations ranged from 0.4 to 6.0 ng/ml over the 24-h period. LH concentrations varied from 0.2 to 12.0 ng/ml. In all animals, LH peaks were clearly followed, after about 50 min, by corresponding testosterone peaks, but no diurnal rhythm could be established. LH concentrations in the castrated dogs were high (9.8 +/- 2.7 (s.e.m.) ng/ml), and still showed an episodic pattern in spite of the undetectable plasma testosterone levels.     

中华倒刺鲃幼鱼能量代谢特征个体差异及生态关联

为了探讨鱼类能量代谢特征个体变异及其生态关联, 以中华倒刺鲃(Spinibarbus sinensis)幼鱼为实验对象, 在25℃条件下测定44尾实验鱼的静止代谢率(Resting metabolic rate, RMR)、力竭运动后峰值代谢率(Peak metabolic rate, PMR)、力竭运动后过量耗氧(Excess post-exercise oxygen consumption, EPOC)、低氧胁迫后峰值代谢率PMR和低氧胁迫后过量耗氧(Excess post-hypoxia oxygen consumption, EPHOC)。研究发现, 中华倒刺鲃能量代谢特征参数存在较大个体差异, RMR、力竭运动后PMR、EPOC、低氧胁迫后PMR和EPHOC分别为193.62—460.33 [mg O₂/(kg·h)]、617.9—2165.02 [mg O₂/(kg·h)]、28.76—267.20 mg O₂/kg、484.3—1142.97 [mg O₂/(kg·h)]和30.27—211.88 mg O₂/kg。力竭运动后PMR(r=0.348, P=0.010)和低氧胁迫后PMR(r=0.449, P=0.002)与RMR间均呈显著正相关; EPOC与RMR间呈显著负相关(r=–0.426, P=0.004), 而EPHOC与RMR间的关系不显著(r=–0.292, P=0.054); 力竭运动后PMR与EPOC间(r=0.424, P=0.004)和低氧胁迫后PMR与EPHOC间(r=0.391, P=0.009)均呈显著正相关。力竭运动后PMR与低氧胁迫后PMR(r=0.673, P<0.001)和EPOC与EPHOC(r=0.526, P<0.001)在个体差异均显著正相关; 然而力竭运动后PMR和EPOC分别显著高于低氧胁迫后PMR与EPHOC(P<0.05)。研究表明: 维持代谢较高的中华倒刺鲃个体有助于其快速提升有氧功率输出以维持高的游泳运动能力; 而较低维持代谢个体具有相对较高的EPHOC有助于机体在极端环境条件下提升其低氧耐受能力。中华倒刺鲃能量特征的个体变异可能是经长期自然选择适应环境的结果。     

Effect of maternal pinealectomy and reverse photoperiod on the circadian melatonin rhythm in the sheep and fetus during the last trimester of pregnancy

The present study tested the hypothesis that the nocturnal melatonin rhythm in the fetal sheep results from transfer across the placenta of melatonin from maternal circulation. Pregnant ewes were exposed to an artificial reverse photoperiod at about 100 days gestation (n = 6; lights on 10 h, 2200-0800 h PST). This treatment tested for entrainment in the ewe and its fetus of the 24-h pattern of melatonin production from the pineal gland. Other ewes were pinealectomized at 55 days post-breeding (n = 6), and similarly treated. Catheters were implanted and blood samples were collected between 117 and 142 days gestation at two 48-h periods, about every 0.5-4 h, to assess the pattern of melatonin in maternal and fetal circulations. In pineal-intact ewes and their fetuses, melatonin rhythms conformed to the reverse photoperiod, i.e. plasma melatonin concentrations were relatively low during the light period and significantly increased for the duration of darkness. In contrast, maternal pinealectomy abolished the melatonin rhythms in both the ewe and fetus; melatonin concentrations remained at or below the limits of detection. Pineal-intact sheep gave birth about 139 +/- 2 days (mean +/- SE, n = 4) at 1915 +/- 0.7 h and pinealectomized ewes (n = 5 of 6) lambed at 149 +/- 2 days at 0424 +/- 0.5 h. Finally, in lambs (n = 3) born to pinealectomized ewes, typical melatonin rhythms were present within the first week of life. The findings indicate that the maternal pineal gland is responsible for the 24-h pattern of melatonin in the ewe and its fetus during the last trimester of pregnancy.     

Activation of dopamine D2 receptors simultaneously ameliorates various metabolic features of obese women

The metabolic syndrome comprises a cluster of metabolic anomalies including insulin resistance, abdominal obesity, dyslipidemia, and hypertension. Previous studies suggest that impaired dopamine D2 receptor (D2R) signaling is involved in its pathogenesis. We studied the acute effects of bromocriptine (a D2R agonist) on energy metabolism in obese women; body weight and caloric intake remained constant. Eighteen healthy, obese women (BMI 33.2 +/- 0.6 kg/m(2), mean age 37.5 +/- 1.7, range 22-51 yr) were studied twice in the follicular phase of their menstrual cycle in a prospective, single-blind, crossover design. Subjects received both placebo (P; always first occasion) and bromocriptine (B; always second occasion) on separate occasions for 8 days. At each occasion blood glucose and insulin were assessed every 10 min for 24 h, and circadian plasma free fatty acid (FFA) and triglyceride (TG) levels were measured hourly. Fuel oxidation was determined by indirect calorimetry. Body weight and composition were not affected by the drug. Mean 24-h blood glucose (P < 0.01) and insulin (P < 0.01) were significantly reduced by bromocriptine, whereas mean 24 h FFA levels were increased (P < 0.01), suggesting that lipolysis was stimulated. Bromocriptine increased oxygen consumption (P = 0.03) and resting energy expenditure (by 50 kcal/day, P = 0.03). Systolic blood pressure was significantly reduced by bromocriptine. Thus these results imply that short-term bromocriptine treatment ameliorates various components of the metabolic syndrome while it shifts energy balance away from lipogenesis in obese humans.     

Effects of chronic oral rimonabant administration on energy budgets of diet-induced obese C57BL/6 mice

The endocannabinoids have been recognized as an important system involved in the regulation of energy balance. Rimonabant (SR141716), a selective inverse agonist of cannabinoid receptor 1 (CB1), has been shown to cause weight loss. However, its suppressive impact on food intake is transient, indicating a likely additional effect on energy expenditure. To examine the effects of rimonabant on components of energy balance, we administered rimonabant or its vehicle to diet-induced obese (DIO) C57BL/6 mice once daily for 30 days, by oral gavage. Rimonabant induced a persistent weight reduction and a significant decrease in body fatness across all depots. In addition to transiently reduced food intake, rimonabant-treated mice exhibited decreased apparent energy absorption efficiency (AEAE), reduced metabolizable energy intake (MEI), and increased daily energy expenditure (DEE) on days 4-6 of treatment. However, these effects on the energy budget had disappeared by days 22-24 of treatment. No chronic group differences in resting metabolic rate (RMR) or respiratory quotient (RQ) (P > 0.05) were detected. Rimonabant treatment significantly increased daily physical activity (PA) levels both acutely and chronically. The increase in PA was attributed to elevated activity during the light phase but not during the dark phase. Taken together, these data suggested that rimonabant caused a negative energy balance by acting on both energy intake and expenditure. In the short term, the effect included both reduced intake and elevated PA but the chronic effect was only on increased PA expenditure.     

Regulation of hindbrain Pyy expression by acute food deprivation, prolonged caloric restriction, and weight loss surgery in mice

PYY is a gut-derived putative satiety signal released in response to nutrient ingestion and is implicated in the regulation of energy homeostasis. Pyy-expressing neurons have been identified in the hindbrain of river lamprey, rodents, and primates. Despite this high evolutionary conservation, little is known about central PYY neurons. Using in situ hybridization, PYY-Cre;ROSA-EYFP mice, and immunohistochemistry, we identified PYY cell bodies in the gigantocellular reticular nucleus region of the hindbrain. PYY projections were present in the dorsal vagal complex and hypoglossal nucleus. In the hindbrain, Pyy mRNA was present at E9.5, and expression peaked at P2 and then decreased significantly by 70% at adulthood. We found that, in contrast to the circulation, PYY-(1-36) is the predominant isoform in mouse brainstem extracts in the ad libitum-fed state. However, following a 24-h fast, the relative amounts of PYY-(1-36) and PYY-(3-36) isoforms were similar. Interestingly, central Pyy expression showed nutritional regulation and decreased significantly by acute starvation, prolonged caloric restriction, and bariatric surgery (enterogastroanastomosis). Central Pyy expression correlated with body weight loss and circulating leptin and PYY concentrations. Central regulation of energy metabolism is not limited to the hypothalamus but also includes the midbrain and the brainstem. Our findings suggest a role for hindbrain PYY in the regulation of energy homeostasis and provide a starting point for further research on gigantocellular reticular nucleus PYY neurons, which will increase our understanding of the brain stem pathways in the integrated control of appetite and energy metabolism.     

Comparison of Methods for Achieving 24‐Hour Energy Balance in a Whole‐Room Indirect Calorimeter

Objective: To evaluate and compare methods for achieving 24‐hour energy balance in a whole‐room indirect calorimeter. Research Methods and Procedures: Twenty‐four‐hour energy expenditure (EE) for 34 healthy adults (16 women, 18 men) was measured in a calorimeter during a prestudy day and on a subsequent nonconsecutive assessment day (AD). Several methods for estimating EE on the AD using activity factors or regression equations with data available before the AD [anthropometrics, body composition, resting metabolic rate (RMR), sleeping metabolic rate (SMR) on prestudy day, 24‐hour EE on prestudy day] were compared for predictive accuracy. Results: Use of a 24‐hour calorimeter stay gave the smallest mean absolute error (119 ± 16 kcal/d) and smallest single maximum error (361 kcal/d). However, several other methods were only slightly, and not significantly, less accurate (e.g., mean absolute error = 131 ± 17, 140 ± 20, and 141 ± 22 kcal/d and greatest error = 384, 370, and 593 kcal/d for anthropometric, RMR, and SMR regression equations, respectively). Fat‐free mass alone and SMR with a simple activity factor were seen to be less accurate. Discussion: Our results indicate that there may be some improvement in achieving 24‐hour energy balance in a metabolic chamber by using a preceding 24‐hour calorimeter stay; that only slightly less accurate predictions can be obtained using a combination of anthropometric, body composition, and/or RMR measurements; and that there is little or no advantage in using SMR from a previous overnight calorimeter stay.     

Visceral fat accumulation determines postprandial lipemic response,lipid peroxidation,DNA damage,and endothelial dysfunction in nonobese Korean men

Visceral fat has been associated with multiple cardiovascular disease (CVD) risk factors. The aim of this study was to identify anthropometrical measures most closely associated with some well-known CVD risk factors. Because most Asians at risk have normal body mass index (BMI) according to Western standards, we studied healthy nonobese Korean males (n = 102; age: 36.5 +/- 0.8 years, BMI: 23.8 +/- 0.2 kg/m2). Visceral fat area (VFA) at the fourth lumbar vertebra was associated with increased postprandial triglyceride (TG) response (r = 0.53, P < 0.001) and with plasma malondialdehyde (MDA) (r = 0.36, P < 0.01) and PGF2alpha (r = 0.24, P < 0.05). When matched for BMI and age, men with high VFA (HVFA) (>/=100 cm2; n = 27) had higher blood pressure (P < 0.01), increased consumption of cigarettes (P < 0.01), and lower ratio of energy expenditure to calorie intake (P < 0.01) as compared with low VFA men (<100 cm2; n = 27). Men with HVFA showed higher TG, glucose, and insulin responses following fat and oral glucose tolerance tests respectively higher plasma concentrations of MDA (P < 0.001), urinary PGF2alpha (P < 0.05), and lymphocytes deoxyribonucleic acid tail moments (P < 0.01). Conversely, HVFA was associated with lower testosterone, insulin-like growth factor-1, and brachial artery flow-mediated dilation (P < 0.001). In conclusion, our data indicate that visceral fat accumulation, even in nonobese men, is a major factor contributing to increased CVD risk.     

24-Hour profiles of circulating ghrelin and peptide YY are inversely associated in normal weight premenopausal women

Peptide YY (PYY) and ghrelin (GHR) may modulate one another's actions within the hypothalamus. Peripheral infusion of PYY in humans acutely suppresses circulating concentrations of GHR. Whether an association between PYY and GHR exists in the peripheral circulation of humans over 24 h is unknown. The purpose of this study was to determine if circulating concentrations of PYY and GHR were significantly associated over 24 h in humans. Participants (n = 13) were normal weight, moderately active, women ages 18–24 yr. Blood samples were obtained q10 min for 24 h and assayed using RIA for total PYY and total GHR hourly from 0800 to 1000 h and 2000 to 0800 h and q20 min from 1000 to 2000 h. Dietary intake during the 24 h procedure was comprised of 55% carbohydrates, 30% fat, and 15% protein (three meals and a snack). Statistical analyses included linear mixed-effects modeling to test whether PYY predicted GHR concentrations over 24 h. Participants weighed 57.0 ± 1.5 kg and had 26.1 ± 1.5% body fat (15.0 ± 1.1 kg), 42.1 ± 1.1 kg fat free mass, a BMI of 21.3 ± 0.5 kg/m² and RMR of 1072 ± 28 kcal/24 h. Visually, PYY and GHR exhibited an inverse association over nearly the entire 24 h period. Statistically, circulating concentrations of 24 h PYY predicted 24 h GHR (ghrelin = 1860.51–2.14*PYY; p = 0.04). Circulating concentrations of PYY are inversely associated with GHR over 24 h. These data provide evidence that PYY may contribute to the modulation of the secretion of GHR in normal weight, premenopausal women over a 24 h period and supports similar inferences from experimental studies in animals and humans.     

Influence of ascorbic acid on the thermic effect of feeding in overweight and obese adult humans

The thermic effect of feeding (TEF: increase in energy expenditure following acute energy intake) is an important physiological determinant of total daily energy expenditure and thus energy balance. Approximately 40% of TEF is believed to be mediated by sympathoadrenal activation and consequent beta-adrenergic receptor stimulation of metabolism. In sedentary adults, acute administration of ascorbic acid, a potent antioxidant, augments the thermogenic response to beta-adrenergic stimulation. We hypothesized that acute ascorbic acid administration augments TEF in sedentary overweight and obese adults. Energy expenditure was determined (ventilated hood technique) before and 4 h after consumption of a liquid-mixed meal (caloric equivalent 40% of resting energy expenditure (REE)) in 11 sedentary, overweight/obese adults (5 men, 6 women; age: 24 +/- 2 years; BMI: 28.5 +/- 1.0 kg/m(2) (mean +/- s.e.)) on two separate, randomly ordered occasions: during continuous intravenous administration of saline (placebo control) and/or ascorbic acid (0.05 g/kg fat-free mass). Acute ascorbic acid administration prevented the increase in plasma concentration of oxidized low-density lipoprotein in the postprandial state (P = 0.04), but did not influence REE (1,668 +/- 107 kcal/day vs.1,684 +/- 84 kcal/day; P = 0.91) or the area under the TEF response curve (33.4 +/- 2.4 kcal vs. 30.5 +/- 3.6 kcal; P = 0.52) (control vs. ascorbic acid, respectively). Furthermore, acute ascorbic acid administration had no effect on respiratory exchange ratio, heart rate, or arterial blood pressure in the pre- and postabsorptive states (all P > 0.64). These data imply that the attenuated TEF commonly observed with sedentary lifestyle and obesity is not modulated by ascorbic acid-sensitive oxidative stress.