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Quantifying phenotypic flexibility as the response to a high-fat challenge test in different states of metabolic health.
Kardinaal, AF, van Erk, MJ, Dutman, AE, Stroeve, JH, van de Steeg, E, Bijlsma, S, Kooistra, T, van Ommen, B, Wopereis, S
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2015;(11):4600-13
Abstract
Metabolism maintains homeostasis at chronic hypercaloric conditions, activating postprandial response mechanisms, which come at the cost of adaptation processes such as energy storage, eventually with negative health consequences. This study quantified the metabolic adaptation capacity by studying challenge response curves. After a high-fat challenge, the 8 h response curves of 61 biomarkers related to adipose tissue mass and function, systemic stress, metabolic flexibility, vascular health, and glucose metabolism was compared between 3 metabolic health stages: 10 healthy men, before and after 4 wk of high-fat, high-calorie diet (1300 kcal/d extra), and 9 men with metabolic syndrome (MetS). The MetS subjects had increased fasting concentrations of biomarkers representing the 3 core processes, glucose, TG, and inflammation control, and the challenge response curves of most biomarkers were altered. After the 4 wk hypercaloric dietary intervention, these 3 processes were not changed, as compared with the preintervention state in the healthy subjects, whereas the challenge response curves of almost all endocrine, metabolic, and inflammatory processes regulating these core processes were altered, demonstrating major molecular physiologic efforts to maintain homeostasis. This study thus demonstrates that change in challenge response is a more sensitive biomarker of metabolic resilience than are changes in fasting concentrations.
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Ultrasonography for the evaluation of visceral fat and the metabolic syndrome.
MeriƱo-Ibarra, E, Artieda, M, Cenarro, A, Goicoechea, J, Calvo, L, Guallar, A, Civeira, F
Metabolism: clinical and experimental. 2005;(9):1230-5
Abstract
Association between abdominal obesity and cardiovascular disease has been related with visceral adiposity, through the predisposition of developing type 2 diabetes mellitus and metabolic syndrome (MS). Sonography is a simple and reliable method to measure both subcutaneous and visceral fat. To analyze the relationship of anthropometric measurements with abdominal adiposity measured by sonography and to analyze the utility of sonography in the prediction of insulin resistance (IR) and the other components of MS. Visceral fat measurements by sonography correlated better with components of MS than did subcutaneous fat measurements. Preperitoneal circumference (PC) was strongly correlated with all components of MS and with IR expressed as a homeostasis model assessment (HOMA) index for IR. PC was better than waist circumference (WC) in predicting triglyceride levels, apolipoprotein B levels, and HOMA index, but WC was better than PC in predicting high-density lipoprotein cholesterol levels. The area under the receiver operating characteristic curve was 0.699 for PC and 0.684 for WC, in subjects with body mass index 25 kg/m2 or greater (P=.024 and .015, respectively). PC and WC showed good correlation with HOMA index (Spearman correlation coefficient=0.306, P<.001 and .206, P<.001, respectively). Abdominal visceral fat is better correlated with MS than subcutaneous fat; sonography is a useful method to evaluate the abdominal fat; PC is the best sonography parameter correlated with components of MS, and in overweight and obese subjects, PC is better than WC at predicting components of the MS.
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Differential effects of metformin and exercise on muscle adiposity and metabolic indices in human immunodeficiency virus-infected patients.
Driscoll, SD, Meininger, GE, Ljungquist, K, Hadigan, C, Torriani, M, Klibanski, A, Frontera, WR, Grinspoon, S
The Journal of clinical endocrinology and metabolism. 2004;(5):2171-8
Abstract
The HIV-lipodystrophy syndrome is associated with fat redistribution and metabolic abnormalities, including insulin resistance (IR). The mechanisms and treatment strategies for IR in HIV-lipodystrophy are unclear, but data suggest that intramuscular lipids contribute to IR in this population. We previously showed that metformin and exercise improve hyperinsulinemia more than metformin alone in HIV-lipodystrophy. Now we investigate the effects of these treatment strategies on thigh muscle adiposity measured by computed tomography and additional body composition measures. Twenty-five HIV-infected patients on stable antiretroviral therapy with hyperinsulinemia and fat redistribution participated in a prospective, randomized, 3-month study of metformin alone or metformin and resistance training three times a week. Thigh muscle adiposity decreased significantly more as shown by increased muscle attenuation [2.0 (range, 0.5-5.0) vs. -1.0 (-3.5-0), P = 0.04] and sc leg fat tended to decrease more [-3.3 (-7.5-4.3) vs. 0.8 (-2.1-9.5), P = 0.06] in the combined treatment group in comparison with metformin alone. In multivariate analysis, change in thigh muscle adiposity remained a significant predictor of change in insulin (P = 0.04), controlling for changes in other body composition measurements. These data suggest that muscle adiposity, in addition to other fat depots, is an important determinant of hyperinsulinemia and that exercise has complex effects on regional fat depots in HIV-infected patients. Reduction in muscle adiposity may be an important mechanism by which exercise improves hyperinsulinemia in this population.
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The effects of exercise training on abdominal visceral fat, body composition, and indicators of the metabolic syndrome in postmenopausal women with and without estrogen replacement therapy: the HERITAGE family study.
Green, JS, Stanforth, PR, Rankinen, T, Leon, AS, Rao Dc, Dc, Skinner, JS, Bouchard, C, Wilmore, JH
Metabolism: clinical and experimental. 2004;(9):1192-6
Abstract
The purpose of this research was to investigate the effects of apriori estrogen replacement therapy (ERT) and endurance exercise training in postmenopausal women on abdominal visceral fat (AFV) and other selected variables related to body composition and the metabolic syndrome (MS). Forty-eight healthy and previously sedentary postmenopausal women (mean age, 54.3 years) who were enrolled in the HERITAGE Family Study (HFS) served as subjects. Of these 48 women, 18 were currently taking ERT and the remaining 30 were taking no supplemental estrogen (NHRT). Computed tomography (CT) scans were used to assess AVF as well as total abdominal fat (TAF) and abdominal subcutaneous fat (ASF). Body mass index (BMI) and waist-to-hip ratios (WHR) were calculated while body fat percentage (%FAT) and total fat mass (FATM) was assessed using underwater weighing. Blood assays for HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), and triglycerides (TG) were conducted at a Centers for Disease Control (CDC) certified laboratory, while blood pressure measurements were assessed using an automated system. All measurements were obtained in duplicate before and after a regimen of endurance exercise training. Analysis of variance (ANOVA) showed AVF to be an average of 31.6 cm(2) less in the women receiving ERT, but lost statistical significance when AVF was adjusted for FATM. Mean values for TAF, ASF, and waist girth were also less in the women receiving ERT, but only waist girth achieved statistical significance. No differences were found in BMI or %FAT, but mean WHR was 5% smaller in the ERT group. Baseline values for HDL-C was higher and LDL-C lower in the ERT group. Prevalence of the MS tended to be greater in the NHRT group, but did not achieve statistical significance. There were no differences in training responses in any of the body composition variables between groups, however, in the ERT group LDL-C decreased with training while TG increased. It was concluded that postmenopausal women taking ERT tended to have lower values of AVF and other indicators of body composition, a more favorable lipid profile, and a slightly reduced risk of the MS when compared with women not taking supplemental hormones. Also exercise training did not improve the overall MS status of either group, as LDL-C status improved in the ERT group while TG decreased in the NHRT group.
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Visceral fat thickness measured by ultrasonography can estimate not only visceral obesity but also risks of cardiovascular and metabolic diseases.
Kim, SK, Kim, HJ, Hur, KY, Choi, SH, Ahn, CW, Lim, SK, Kim, KR, Lee, HC, Huh, KB, Cha, BS
The American journal of clinical nutrition. 2004;(4):593-9
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Abstract
BACKGROUND Visceral obesity is closely associated with cardiovascular disease and the metabolic syndrome. Estimating the amount of visceral fat is important and requires a straightforward, reliable, and practical method. OBJECTIVE We investigated whether visceral fat thickness (VFT) measured by ultrasonography can adequately assess visceral fat accumulation and predict cardiovascular or metabolic diseases. DESIGN Diabetic patients (240 men and 106 women) underwent ultrasonography to estimate visceral fat accumulation. RESULTS The visceral adipose tissue area had the best correlation with VFT (r = 0.799, P < 0.001). VFT correlated with HDL-cholesterol, triacylglycerol, and high-sensitivity C-reactive protein concentrations, the homeostasis model assessment for insulin resistance, and the intima-media thickness at the common carotid artery (r = -0.30, 0.39, 0.34, 0.31, and 0.33, respectively; P < 0.05) in men and with triacylglycerol and high-sensitivity C-reactive protein concentrations and the homeostasis model assessment for insulin resistance (r = 0.33, 0.44, and 0.30, respectively; P < 0.05) in women. Men in the middle and high VFT tertiles had a higher odds ratio (OR) of coronary artery disease [ORs: 4.48 (95% CI: 1.29, 5.51) and 2.04 (1.06, 3.94), respectively; P = 0.016], hypertriacylglycerolemia [ORs: 2.87 (1.41, 5.86) and 1.91 (1.24, 2.95), respectively; P = 0.003], and the metabolic syndrome [ORs: 3.38 (1.61, 7.10) and 1.95 (1.16, 3.27), respectively; P = 0.003] than did those in the low tertile, after adjustment for age, waist circumference, and body mass index. CONCLUSION VFT might be a reliable index for assessing the amount of visceral fat and for identifying diabetic patients, particularly men, who are at high risk of cardiovascular disease.
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Changes in abdominal subcutaneous fat water content with rapid weight loss and long-term weight maintenance in abdominally obese men and women.
Laaksonen, DE, Nuutinen, J, Lahtinen, T, Rissanen, A, Niskanen, LK
International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity. 2003;(6):677-83
Abstract
OBJECTIVE Insulin resistance decreases blood flow and volume in fat tissue. We hypothesised that fat tissue nutritive blood flow and volume, and thereby water content, would increase during weight loss and weight maintenance in obese persons. DESIGN Longitudinal clinical intervention with a 9-week very-low-calorie diet (VLCD) followed by one year of weight maintenance. SUBJECTS Obese men (n=13) and women (n=14) with the metabolic syndrome. MEASUREMENTS Water content of abdominal subcutaneous fat tissue as estimated by a sensor on the skin surface measuring the dielectric constant at 300 MHz. Anthropometric measures of fatness and fat distribution. Biochemical measures related to insulin resistance. RESULTS Subjects lost 14.5+/-3.4% of body weight during the VLCD, and generally sustained this weight loss during weight maintenance. Insulin sensitivity as estimated by an index (qualitative insulin sensitivity check index) increased during the VLCD, and remained increased throughout weight maintenance. The dielectric constant increased from 23.3+/-2.3 to 25.0+/-2.1 (P<0.001) during the VLCD, and further to 27.8+/-1.9 (P<0.001) during weight maintenance, indicating an increase in the water content of subcutaneous fat. The increase in subcutaneous fat water content did not correlate with weight loss and other measures of adiposity during the VLCD, but there was an inverse correlation that strengthened in significance from baseline to 6, 9 and 12 mo (r=-0.32 to -0.64, P=0.079-0.002). Increases in subcutaneous fat water content also correlated with improvements in insulin sensitivity at 6, 9 and 12 months of weight maintenance (r=0.34-0.54, P=0.094-0.006). CONCLUSIONS Water content of abdominal subcutaneous adipose tissue increases with weight loss in obese persons with the metabolic syndrome, and may reflect increased subcutaneous fat tissue nutritive blood flow. The increase in water content correlates with the increase in insulin sensitivity, suggesting that weight loss and consequent improved insulin sensitivity could mediate the increase in abdominal subcutaneous fat hydration.
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[Evaluation of leptin levels in plasma and their reliance on other hormonal factors affecting tissue fat levels in people with various levels of endogenous cotisol].
Robaczyk, MG
Annales Academiae Medicae Stetinensis. 2002;:283-300
Abstract
The discovery of leptin (LEP) shed new light on mechanisms regulating body fat mass (BFM). In this aspect, interactions between LEP and glucocorticoids at hypothalamic level may be of great importance. Factors that influence plasma LEP levels have not been fully recognized and available data on LEP levels are often inconsistent. The aim of this study was to evaluate absolute and BFM-corrected plasma LEP levels and their diurnal variation, as well as to assess the relationship between LEP levels, body fat distribution, and hormones influencing body fat in subjects with various levels of endogenous cortisol and different nutritional status. Group I was composed of 14 women aged 14-58 yrs, BMI of 23.9-37.1 kg/m2, with hypercortisolism due to ACTH-dependent and ACTH-independent Cushing's syndrome (CUS). 17 women with visceral obesity (OTY) and normal or disturbed carbohydrate metabolism, i.e. impaired glucose tolerance (IGT) and diabetes mellitus (DM), aged 24 do 50 yrs, BMI 30.0-46.1 kg/m2, were included in group II. Group III consisted of 14 women with Addison's disease (AD), aged 18 do 63 yrs, BMI 15.4-31.6 kg/m2. The control group IV (KON) included 17 healthy women with normal BMI. BMI, WHR, body composition, and body fat distribution (DEXA method) were assessed in all subjects. Basal plasma levels of LEP, beta-endorphin (B-EP), cortisol (F), insulin-like growth factor-1 (IGF-1) were measured with RIA test kits. Plasma adrenocorticotrophin (ACTH) levels, serum levels of insulin (IRI) and growth hormone (GH) were measured with IRMA test kits. Blood glucose (G) concentration was determined with an enzymatic method. Adiposity-corrected LEP levels were expressed as LEP/BFM and LEP/%BF indices. Fasting insulin resistance index (FIRI) was also calculated. Higher BFM and %BF values were found in the OTY group as compared with CUS KON and AD groups. BFM distribution did not differ in KON and AD groups whereas CUS subjects exhibited a higher accumulation of fat in the trunk when compared to OTY subjects. Absolute LEP levels were correlated with trunk BF in CUS patients whereas in KON and AD groups these levels were correlated only with limb fat. Absolute LEP levels in CUS and OTY groups were comparable, whereas LEP/BFM and LEP/%BF indices were higher in the CUS group (Table 1) reflecting upregulation of LEP levels (Figs. 1, 2). BFM-corrected LEP levels were comparable in groups with normal cortisolemia, i.e. in OTY and KON groups, whereas in the AD group both absolute and BFM-corrected LEP levels were lower than in controls. No correlation was found between plasma levels of F and LEP in CUS and AD groups. This correlation was negative in KON (Fig. 3) and positive in OTY groups (Fig. 4). Moreover, KON and AD groups demonstrated a negative correlation between plasma ACTH and LEP levels. CUS patients showed positive, BFM-independent correlations between LEP levels, FIRI and G values, and a positive, BFM-dependent correlation between IRI and LEP levels. OTY patients exhibited a BFM-dependent positive correlation between FIRI and LEP levels. In these and in AD patients, a positive, BFM-independent correlation between IRI and LEP levels was found. Moreover, a negative, BFM-dependent correlation between GH and LEP levels was found in OTY patients. In this group, B-EP levels were positively correlated with LEP/BFM and LEP/%BF indices (Fig. 5). A negative correlation between LEP levels, LEP/BFM and LEP/%BF indices was ascertained in the AD group. In CUS, OTY, and KON groups, but not in the AD group, a midnight increase in leptin levels was observed. In conclusion, upregulation of leptin levels in relation to body fat in Cushing's syndrome is independent of the source of hypercortisolism. Apparently, it results from insulin resistance and hyperglycaemia and contributes to coexisting metabolic abnormalities. In Addison's disease, downregulation of leptin may reflect an adaptation mechanism to cortisol deficiency and result from low insulin and extremely high adrenocorticotrophin levels. In women with normal cortisol levels, irrespectively of nutritional status; leptin levels reflect body fat content. In obese subjects, leptin levels may be influenced by cortisol levels, high levels of insulin, IGF-1, and beta-endorphin as well as low levels of growth hormone. Disturbed function of hypothalamic-pituitary-adrenal axis (CUS, AD) does not directly influence diurnal variation in plasma leptin levels. In Cushing's syndrome, visceral fat may be a predominant source of leptin, whereas in women with normal or low cortisol levels peripherally accumulated fat may determine leptin secretion.
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Fat distribution and metabolic changes are strongly correlated and energy expenditure is increased in the HIV lipodystrophy syndrome.
Kosmiski, LA, Kuritzkes, DR, Lichtenstein, KA, Glueck, DH, Gourley, PJ, Stamm, ER, Scherzinger, AL, Eckel, RH
AIDS (London, England). 2001;(15):1993-2000
Abstract
OBJECTIVE To examine the relationships between protease inhibitor (PI) therapy, body fat distribution and metabolic disturbances in the HIV lipodystrophy syndrome. DESIGN Cross-sectional study. SETTING HIV primary care practices. PATIENTS PI-treated patients with lipodystrophy (n= 14) and PI-treated (n= 13) and PI-naive (n= 5) patients without lipodystrophy. MAIN OUTCOME MEASURES Body composition was assessed by physical examination, dual-energy X-ray absorptiometry and computed tomography. Insulin sensitivity (SI) was measured using the insulin-modified frequently sampled intravenous glucose tolerance test. Lipid profiles, other metabolic parameters, duration of HIV infection, CD4 lymphocyte counts, HIV-1 RNA load and resting energy expenditure (REE) were also assessed. RESULTS PI-treated patients with lipodystrophy were significantly less insulin sensitive than PI-treated patients and PI-naive patients without any changes in fat distribution (SI(22) x 10(-4) (min(-1)/microU/ml) versus 3.2 x 10(-4) and 4.6 x 10(-4) (min(-1)/microU/ml), respectively; P < 0.001). Visceral adipose tissue area and other measures of central adiposity correlated strongly with metabolic disturbances as did the percent of total body fat present in the extremities; visceral adipose tissue was an independent predictor of insulin sensitivity and high density lipoprotein cholesterol levels. REE per kg lean body mass was significantly higher in the group with lipodystrophy compared to the groups without lipodystrophy (36.9 versus 31.5 and 29.4 kcal/kg lean body mass; P < 0.001), and SI was strongly correlated with and was an independent predictor of REE in this population. CONCLUSIONS Body fat distribution and metabolic disturbances are strongly correlated in the HIV lipodystrophy syndrome and REE is increased.
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Visceral adipose tissue and metabolic complications of obesity are reduced in Prader-Willi syndrome female adults: evidence for novel influences on body fat distribution.
Goldstone, AP, Thomas, EL, Brynes, AE, Bell, JD, Frost, G, Saeed, N, Hajnal, JV, Howard, JK, Holland, A, Bloom, SR
The Journal of clinical endocrinology and metabolism. 2001;(9):4330-8
Abstract
Visceral obesity is detrimental to health, but the mechanisms controlling body fat distribution are not fully understood. In premenopausal adult females (30 nonobese, 14 obese [body mass index >30 kg/m(2)]), variance in fasting insulin, glucose, insulin/glucose ratio, C-peptide/insulin ratio, triglycerides, and high-density lipoprotein/low-density lipoprotein-cholesterol ratio, were independently influenced by visceral but not total sc or abdominal sc adipose tissue, as measured by whole-body magnetic resonance imaging. Adult females with Prader-Willi syndrome (n = 13) had significantly reduced visceral adiposity, compared with obese controls (visceral/total sc adipose tissue ratio: 0.067 +/- 0.017 vs. 0.108 +/- 0.021), independent of their total adiposity (P < 0.001), or use of exogenous sex steroids. This is in contrast to that expected by their physical inactivity, hypogonadism, adult GH deficiency, and psychiatric problems. Females with Prader-Willi syndrome not receiving sex steroids (n = 8) had significantly reduced fasting insulin, insulin/glucose ratio, and triglycerides and increased C-peptide/insulin ratio, compared with obese controls, adjusting for total (P < 0.05) but not visceral adiposity (P = 0.3-0.6), supporting their association. The cause of the reduced visceral adiposity in Prader-Willi syndrome may reflect novel hormonal, hypothalamic, and/or genetic influences on body fat distribution.