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Biomedical subjects

F X Pi-Sunyer

Publications and source records attributed to F X Pi-Sunyer.

At least 19 recordsLinked to original sources

High-fat diet feeding elevates skeletal muscle uncoupling protein 3 levels but not its activity in rats.

OBJECTIVE: The objective of this study is to test the impact of high-fat diet (HFD) feeding on skeletal muscle (SM) uncoupling protein 3 (UCP3) expression and its association with mitochondrial ion permeability and whole-body energy homeostasis. RESEARCH METHODS AND PROCEDURES: Sprague-Dawley rats were fed ad libitum either a HFD (60% of energy from fat, n = 6) or a low-fat diet (12% of energy from fat, n = 6) for 4 weeks. Twenty-four-hour energy expenditure was measured by indirect calorimetry in the last week of the dietary treatment. Blood samples were collected for plasma leptin and free fatty acid assays, and mitochondria were isolated from hindlimb SM for subsequent determinations of UCP3 levels and mitochondrial ion permeability. RESULTS: Plasma leptin levels were higher in rats fed the HFD despite the same body weight in two groups. The same dietary treatment also rendered a 2-fold increase in plasma free fatty acid and SM UCP3 protein levels (Western blot) compared with the group fed the low-fat diet. However, the elevated UCP3 protein levels did not correlate with mitochondrial swelling rates, a measure of mitochondrial chloride, and proton permeability, or with 24-hour energy expenditure. DISCUSSION: The high correlation between the levels of plasma free fatty acid levels and SM UCP3 suggests that circulating free fatty acid may play an important role in UCP3 expression during the HFD feeding. However, the dissociation between the UCP3 protein levels and 24-hour energy expenditure as well as mitochondrial ion permeability suggests that mitochondrial proton leak mediated by muscle UCP3 may not be a major contributor in energy balance in HFD feeding, and other regulatory mechanisms independent of gene regulation may be responsible for the control of UCP3-mediated uncoupling activity.

Animals↗

Impaired insulin action in subcutaneous adipocytes from women with visceral obesity.

Visceral obesity is associated with resistance to the antilipolytic effect of insulin in vivo. We investigated whether subcutaneous abdominal and gluteal adipocytes from viscerally obese women exhibit insulin resistance in vitro. Subjects were obese black and white premenopausal nondiabetic women matched for visceral adipose tissue (VAT), total adiposity, and age. Independently of race and adipocyte size, increased VAT was associated with decreased sensitivity to insulin's antilipolytic effect in subcutaneous abdominal and gluteal adipocytes. Absolute lipolytic rates at physiologically relevant concentrations of insulin or the adenosine receptor agonist N(6)-(phenylisopropyl)adenosine were higher in subjects with the highest vs. lowest VAT area. Independently of cell size, abdominal adipocytes were less sensitive to the antilipolytic effect of insulin than gluteal adipocytes, which may partly explain increased nonesterified fatty acid fluxes in upper vs. lower body obese women. Moreover, increased VAT was associated with decreased responsiveness, but not decreased sensitivity, to insulin's stimulatory effect on glucose transport in abdominal adipocytes. These data suggest that insulin resistance of subcutaneous abdominal and, to a lesser extent, gluteal adipocytes may contribute to increased systemic lipolysis in both black and white viscerally obese women.

Abdomen↗

Magnitude and variation of ratio of total body potassium to fat-free mass: a cellular level modeling study.

Potassium is an essential element of living organisms that is found almost exclusively in the intracellular fluid compartment. The assumed constant ratio of total body potassium (TBK) to fat-free mass (FFM) is a cornerstone of the TBK method of estimating total body fat. Although the TBK-to-FFM (TBK/FFM) ratio has been assumed constant, a large range of individual and group values is recognized. The purpose of the present study was to undertake a comprehensive analysis of biological factors that cause variation in the TBK/FFM ratio. A theoretical TBK/FFM model was developed on the cellular body composition level. This physiological model includes six factors that combine to produce the observed TBK/FFM ratio. The ratio magnitude and range, as well as the differences in the TBK/FFM ratio between men and women and variation with growth, were examined with the proposed model. The ratio of extracellular water to intracellular water (E/I) is the major factor leading to between-individual variation in the TBK/FFM ratio. The present study provides a conceptual framework for examining the separate TBK/FFM determinants and suggests important limitations of the TBK/FFM method used in estimating total body fat in humans and other mammals.

Adipose Tissue↗

A randomized trial of improved weight loss with a prepared meal plan in overweight and obese patients: impact on cardiovascular risk reduction.

OBJECTIVE: To assess the long-term effects of a prepackaged, nutritionally complete, prepared meal plan compared with a usual-care diet (UCD) on weight loss and cardiovascular risk factors in overweight and obese persons. DESIGN: In this randomized multicenter study, 302 persons with hypertension and dyslipidemia (n = 183) or with type 2 diabetes mellitus (n = 119) were randomized to the nutrient-fortified prepared meal plan (approximately 22% energy from fat, 58% from carbohydrate, and 20% from protein) or to a macronutrient-equivalent UCD. MAIN OUTCOME MEASURES: The primary outcome measure was weight change. Secondary measures were changes in blood pressure or plasma lipid, lipoprotein, glucose, or glycosylated hemoglobin levels; quality of life; nutrient intake; and dietary compliance. RESULTS: After 1 year, weight change in the hypertension/dyslipidemia group was -5.8+/-6.8 kg with the prepared meal plan vs -1.7+/-6.5 kg with the UCD plan (P<.001); for the type 2 diabetes mellitus group, the change was -3.0+/-5.4 kg with the prepared meal plan vs -1.0+/-3.8 kg with the UCD plan (P<.001) (data given as mean +/- SD). In both groups, both interventions improved blood pressure, total and low-density lipoprotein cholesterol levels, glycosylated hemoglobin level, and quality of life (P<.02); in the diabetic group, the glucose level was reduced (P<.001). Compared with those in the UCD group, participants with hypertension/dyslipidemia in the prepared meal plan group showed greater improvements in total (P<.01) and high-density lipoprotein (P<.03) cholesterol levels, systolic blood pressure (P<.03), and glucose level (P<.03); in participants with type 2 diabetes mellitus, there were greater improvements in glucose (P =.046) and glycosylated hemoglobin (P<.02) levels. The prepared meal plan group also showed greater improvements in quality of life (P<.05) and compliance (P<.001) than the UCD group. CONCLUSIONS: Long-term dietary interventions induced significant weight loss and improved cardiovascular risk in high-risk patients. The prepared meal plan simultaneously provided the simplicity and nutrient composition necessary to maintain long-term compliance and to reduce cardiovascular risk.

Adult↗

Factors affecting blood pressure responses to diet: the Vanguard study.

To study physiologic factors affecting the blood pressure (BP) response to nonpharmacologic maneuvers, fasting blood glucose, insulin, lipid and mineral levels, urinary mineral excretion, and the calcium regulating hormones parathyroid hormone (PTH) and 1,25 dihydroxyvitamin D (1,25 (OH)2D) were measured in 71 unmedicated hypertensive (26 hypertensive only [HT], 45 hypertensive hyperlipidemic [HTHL]), and 87 normotensive hyperlipidemic (NTHL) control subjects before and during a 10-week multicenter, randomized controlled trial comparing a prepared meal plan (CCNW) with a self-selected diet (SSD) based on nutritionist counseling. Blood pressure fell to a greater extent in hypertensive versus normotensive subjects (-8+/-1/-5+/-1 v -2+/-1/-2+/-1 mm Hg, P < .0001/P < .0001), and on CCNW versus SSD diets (delta systolic BP [SBP]/delta diastolic BP [DBP], P = .033/P = .002). Diet-induced weight change was the strongest correlate of changes in BP (SBP: r = 0.360, P < .0001; DBP: r = 0.414, P < .0001), which, on multivariate analysis for deltaSBP, could partly be accounted for by diet-induced changes in fasting glucose (r = 0.215, P = .009) and cholesterol (r = 0.219, P = .006) levels. Independently of weight, diet-induced changes in SBP also were significantly related to concomitant changes in urinary excretion of potassium (r = -0.285, P = .001), magnesium (r = -0.254, P = .003), and calcium relative to sodium (r = -0.200, P = .021), but not to sodium per se; and to changes in serum potassium (r = -0.249, P = .002), phosphorus (r = -0.279, P = .001), PTH (r = 0.288, P = .0006), and 1,25 D (r = 0.202, P = .017). We conclude that the ability of diet to lower BP successfully may result from the additive contributions of multiple components. Independently of weight loss and the associated changes in circulating glucose and cholesterol, BP is influenced by the increasing provision of minerals such as potassium, magnesium, and calcium, perhaps by virtue of their suppressive effects on circulating vasoactive calcium regulating hormones.

Adult↗

Obesity: criteria and classification.

Obesity is defined as an excess accumulation of body fat. To measure fat in the body accurately is difficult, and no method is easily available for routine clinical use. Traditionally, overweight and obesity have been evaluated by anthropometric measurement of weight-for-height. More recently, BMI has been used. The normal range is 19-24.9 kg/m2, overweight is 25-29.9 kg/m2, and obesity >/= 30 kg/m2. Not only is the total amount of fat an individual carries important, but also where the fat is distributed in the body. Fat in a central or upper body (android) distribution is most related to health risk. The most accurate way to measure central obesity is by magnetic resonance imaging or computer-assisted tomography scanning, but this approach is too expensive for routine use. Simple anthropometric measurements can be used, such as waist circumference. A waist circumference of greater than 1020 mm in men and 880 mm in women is a risk factor for insulin resistance, diabetes mellitus and cardiovascular disease. There is a clear genetic predisposition for obesity. The genetic contribution to obesity is between 25 and 40 % of the individual differences in BMI. For the overwhelming majority of individuals, the genetic predisposition will not be defined by one gene, but by multiple genes. Eventually, classification of obesity may be done by genetic means, but this approach will require more knowledge.

Adipose Tissue↗

Effect of one morning meal and a bolus of dexamethasone on 24-hour variation of serum leptin levels in humans.

OBJECTIVE: We have previously shown that morning administration of dexamethasone in combination with food induces a doubling of serum leptin levels starting at 7 hours after dexamethasone administration, with a maximum effect at 10 hours, the latest time point that we have studied. However, dexamethasone given in the absence of food had no effect on serum leptin at 10 hours. The present experiment was undertaken to determine the duration of the effect of dexamethasone on 24-hour serum leptin under fasted and fed conditions in humans. RESEARCH METHODS AND PROCEDURES: Six healthy non-obese male volunteers were studied under the following four conditions: 1) dexamethasone (2 mg intravenously, given at 0900 hours) with fasting; 2) dexamethasone with food (1,700 kcal, 55% carbohydrate, 15% protein, and 30% fat, given in one meal 2 hours after dexamethasone administration at 1100 hours); 3) saline with food (same meal); 4) saline with fasting. Serum leptin, glucose, insulin, and cortisol were monitored every 30 minutes for 24 hours. RESULTS: 1) Under the fasting condition, dexamethasone increased leptin nocturnal secretion between 2100 and 2400 hours. 2) A single meal (1,700 kcal) at 1100 hours increased nocturnal leptin secretion when compared with the fasting condition. The peak increase of leptin was 123% over baseline between 2100 and 2400 hours, 10 to 14 hours after the meal. 3) In the fed + dexamethasone condition, leptin levels increased from baseline starting 8 hours after dexamethasone injection, reached a maximum increase of 260% between 2100 and 2400 hours, then decreased thereafter, remaining elevated compared to baseline for 16 hours. There was a correlation between 24-hour leptin secretion and insulin secretion after a single morning meal. DISCUSSION: A single bolus of dexamethasone, given before a single large meal, produces a delayed (6-hour) but long-lasting increase in serum leptin (over 16 hours). Under fasted conditions, dexamethasone does not increase daytime leptin but does increase leptin during the night.

Adult↗

Overnutrition and undernutrition as modifiers of metabolic processes in disease states.

Both overnutrition and undernutrition affect energy metabolism, with overnutrition raising energy expenditure and undernutrition lowering it. Fever is a powerful stimulator of thermogenesis. In diseases such as cancer, AIDS, diabetes mellitus, and rheumatoid arthritis, whether energy expenditure is increased or decreased often depends on how advanced the disorder is. Early on, when the greater protein turnover characteristic of these conditions is paramount, energy expenditure is increased. In addition, in diseases such as cancer, AIDS, and rheumatoid arthritis in which cytokines are released, the cytokines' thermogenic effect initially increases the metabolic rate. However, as the disease becomes more advanced and leads to cachexia, energy expenditure drops below normal. Acute conditions such as burns and trauma significantly raise energy expenditure, primarily by increasing sympathetic response and the release of catecholamines, which are powerful stimulators of energy expenditure.

Acquired Immunodeficiency Syndrome↗

Total body calcium in obese women. Validation of dual-energy X-ray absorptiometry against in vivo neutron activation analysis.

In vivo neutron activation analysis (IVNA) allows in vivo measurement of total body calcium and is considered the gold standard technique. Dual-energy X-ray absorbtiometry (DXA) estimates total body calcium. Although there are a few comparisons of the two techniques, there are none with obese women. The present study compared the estimation of total body calcium by DXA with the measurement of Ca by IVNA in 69 obese women. Sixty-nine obese women (age 44 +/- 10 years, body weight [BW] 93 +/- 10.4 kg, body mass index [BMI] 35 +/- 4, fat mass 42 +/- 7 kg, 48 pre- and 21 postmenopausal, 30 Caucasian and 39 African-American) were recruited for a six-month body composition study without weight loss intervention. Total body (TB) Ca was measured by IVNA (CaIVNA) and by DXA (CaDXA) at baseline (n = 69) and again at six months (n = 40). At baseline, CaDXA was significantly higher than CaIVNA (1018 +/- 130 g vs. 706 +/- 92 g, p = 0.0001). The difference remained after six months (1028 +/- 153 g vs. 715 +/- 96 g). There was a small but significant increase in TBCa at six months by both DXA (16.5 +/- 40, p < 0.02) and IVNA (8 +/- 22 g, p < 0.03). However, this change was not significantly different between the two methods (p = 0.2365). The correlation between the two methods was very high (r = 0.937) and was independent of either race or menopausal status (p = 0.5163). We generated a regression equation: CaIVNA = 0.659 x CaDXA + 34.77; SEE = 32.2, R = 0.937. We present a model integrating the effect of weight and height on the relationship between CaIVNA and CaDXA. The higher the BMI, the bigger the difference between CaIVNA and CaDXA. In our population with a mean BMI of 35.3, CaIVNA = 69% CaDXA.

Absorptiometry, Photon↗

Weight stability masks sarcopenia in elderly men and women.

Skeletal muscle loss or sarcopenia in aging has been suggested in cross-sectional studies but has not been shown in elderly subjects using appropriate measurement techniques combined with a longitudinal study design. Longitudinal skeletal muscle mass changes after age 60 yr were investigated in independently living, healthy men (n = 24) and women (n = 54; mean age 73 yr) with a mean +/- SD follow-up time of 4.7 +/- 2.3 yr. Measurements included regional skeletal muscle mass, four additional lean components (fat-free body mass, body cell mass, total body water, and bone mineral), and total body fat. Total appendicular skeletal muscle (TSM) mass decreased in men (-0.8 +/- 1.2 kg, P = 0.002), consisting of leg skeletal muscle (LSM) loss (-0.7 +/- 0.8 kg, P = 0.001) and a trend toward loss of arm skeletal muscle (ASM; -0.2 +/- 0.4 kg, P = 0.06). In women, TSM mass decreased (-0.4 +/- 1.2 kg, P = 0.006) and consisted of LSM loss (-0.3 +/- 0.8 kg, P = 0.005) and a tendency for a loss of ASM (-0.1 +/- 0.6 kg, P = 0.20). Multiple regression modeling indicates greater rates of LSM loss in men. Body weight in men at follow-up did not change significantly (-0.5 +/- 3.0 kg, P = 0.44) and fat mass increased (+1.2 +/- 2.4 kg, P = 0.03). Body weight and fat mass in women were nonsignificantly reduced (-0.8 +/- 3.9 kg, P = 0.15 and -0.8 +/- 3.5 kg, P = 0.12). These observations suggest that sarcopenia is a progressive process, particularly in elderly men, and occurs even in healthy independently living older adults who may not manifest weight loss.

Absorptiometry, Photon↗

Nutritionally complete prepared meal plan to reduce cardiovascular risk factors: a randomized clinical trial.

OBJECTIVE: To compare a nutritionally complete prepared meal plan that meets national dietary guidelines to usual-care dietary therapy for hypertension, dyslipidemia, and glycemic control. DESIGN: Randomized, controlled trial. SUBJECTS/SETTING: Outpatients with hypertension, dyslipidemia, or diabetes mellitus (n = 251) were recruited at 6 medical centers in the United States and Canada. INTERVENTION: The prepared meal plan, which was developed by university-based nutrition and cardiovascular scientists and food technologists at Campbell's Center for Nutrition & Wellness (CCNW), provided the optimal levels of macronutrients and micronutrients recommended for cardiovascular risk reduction in a variety of prepackaged meals and snacks. After a 4-week pretrial period to assess baseline state, participants were randomized to the CCNW plan or "usual-care" diet for 10 weeks. MAIN OUTCOME MEASURES: Blood pressure, carbohydrate metabolism, lipoproteins, homocysteine, weight, nutrient intake, compliance. STATISTICAL ANALYSES PERFORMED: Repeated measures analysis of variance. RESULTS: Lipoproteins, carbohydrate metabolism, blood pressure, and weight improved on both plans. Mean differences (+/- standard deviation) between baseline and follow-up for the CCNW plan and the usual-care plan, respectively, were total cholesterol, -0.41 +/- 0.64 and -0.20 +/- 0.50 mmol/L (between-group P < .01); plasma glucose, -0.7 +/- 1.7 and -0.3 +/- 1.3 mmol/L (P < .05); systolic blood pressure, -5.2 +/- 10.0 and -4.7 +/- 9.0 mm Hg (P = .67), diastolic blood pressure, -3.8 +/- 5.9 and -2.2 +/- 5.5 mm Hg (P < .05); and homocysteine, -1.3 +/- 3.8 and 0.2 +/- 3.4 mumol/L (P < .01). The CCNW plan led to greater weight loss than the usual-care diet (-5.5 +/- 3.8 kg vs -3.0 +/- 3.2 kg, P < .0001). APPLICATIONS/CONCLUSION: The nutritionally complete CCNW plan offers greater improvements in lipids, blood sugars, homocysteine, and weight loss than usual-care diet therapy. This prepackaged comprehensive nutrition program can augment both the prescription and practice of optimal dietary therapy.

Adult↗

Insulin sensitivity and serum triglyceride level in obese white and black women: relationship to visceral and truncal subcutaneous fat.

Although independent associations of visceral fat with the insulin resistance syndrome were previously reported in obese women, the importance of truncal subcutaneous fat with regard to insulin sensitivity is still controversial. We measured the insulin sensitivity index (S(I)), serum triglyceride (TG) level, and regional fat by two methods: (1) the sum of five truncal and four peripheral skinfolds (TrSUM and PerSUM) in 38 white and black obese nondiabetic premenopausal women, and (2) abdominal visceral (VFM) and subcutaneous fat mass (AbdSCFM) by a combination of magnetic resonance imaging (MRI) and dual x-ray absorptiometry (DXA) in a subset of 26 of these women. After adjusting for the total body fat mass, TrSUM and VFM were independently and negatively related to S(I) (n = 38, P < .012 and n = 26, P < .035, respectively), whereas PerSUM and AbdSCFM were not related (P > .50). Based on multiple regression modeling, TrSUM significantly predicted S(I) independently of the VFM (n = 26, P < .001). Black women had lower S(I) at all levels of TrSUM (n = 38, P = .061 for the slope and P = .03 for the intercept of the regression lines). After adjusting for the total body fat mass, only VFM showed an independent positive relation to serum TG, and race did not affect this relationship (n = 26, P < .001). In conclusion, (1) we confirmed the independent association of the VFM with insulin resistance and elevated TG in obese women; (2) the AbdSCFM measured by a combination of MRI and DXA did not show an independent association with S(I) in obese women; and (3) the independent association of TrSUM with S(I) suggests that truncal subcutaneous fat depots contribute to insulin resistance in obese women independently of the degree of visceral fat.

Absorptiometry, Photon↗

Weight loss increases and fat loss decreases all-cause mortality rate: results from two independent cohort studies.

OBJECTIVE: In epidemiological studies, weight loss is usually associated with increased mortality rate. Contrarily, among obese people, weight loss reduces other risk factors for disease and death. We hypothesised that this paradox could exist because weight is used as an implicit adiposity index. No study has considered the independent effects of weight loss and fat loss on mortality rate. We studied mortality rate as a function of weight loss and fat loss. DESIGN: Analysis of 'time to death' in two prospective population-based cohort studies, the Tecumseh Community Health Study (1890 subjects; 321 deaths within 16y of follow-up) and the Framingham Heart Study (2731 subjects; 507 deaths within 8y of follow-up), in which weight and fat (via skinfolds) loss were assessable. RESULTS: In both studies, regardless of the statistical approach, weight loss was associated with an increased, and fat loss with a decreased, mortality rate (P < 0.05). Each standard deviation (s.d.) of weight loss (4.6 kg in Tecumseh, 6.7 kg in Framingham) was estimated to increase the hazard rate by 29% (95% confidence interval CI), (14%, 47%, respectively) and 39% (95% CI, 25%, 54% respectively), in the two samples. Contrarily, each s.d. of fat loss (10.0 mm in Tecumseh, 4.8 mm in Framingham) was estimated to reduce the hazard rate 15% (95% CI, 4%, 25%) and 17% (95% CI, 8%, 25%) in Tecumseh and Framingham, respectively. Generalisability of these results to severely (that is, body mass index BMI) > or = 34) obese individuals is unclear. CONCLUSIONS: Among individuals that are not severely obese, weight loss is associated with increased mortality rate and fat loss with decreased mortality rate.

Adipose Tissue↗