Metabolism - Clinical and Experimental

Masthead

2012-02-01

Dietary calcium and body weight: what's the “skinny”?

Catherine M. Gordon, Christos S. Mantzoros — 2012-02-01

There has been growing interest in mechanisms underlying the observation that high dietary calcium intake may attenuate weight gain. Both animal and human studies have explored this association . However, the metabolic alterations that explain this phenomenon remain unclear, as are the molecular mechanisms that may be at play. This month's article by Zhang et al provides new insights into this question.

Metabolic syndrome in a Mediterranean pediatric cohort: prevalence using International Diabetes Federation–derived criteria and associations with adiponectin and leptin

Constantina Papoutsakis, Mary Yannakoulia, Ioanna Ntalla, George V. Dedoussis — 2011-08-04

Abstract: The aims of the study were to determine the prevalence of metabolic syndrome (MS) components and examine associations with adipokine concentrations in a healthy pediatric cohort. A cross-sectional study of 1138 children (53% girls; mean age of all participants, 11.2 ± 0.7 years) was performed. Anthropometric and medical information was obtained; and a fasting blood sample was used to measure glucose, insulin, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, leptin, and adiponectin serum concentrations. Insulin resistance was assessed by the insulin resistance homeostasis model assessment. Body weight status (normal, overweight, and obese) was determined according to the International Obesity Task Force. Estimation of the MS was based on the International Diabetes Federation definition. The prevalence of the MS was 0.7% of children, all of whom were obese. Frequency of abdominal obesity, high fasting glucose, elevated triglycerides, low high-density-lipoprotein cholesterol, and elevated blood pressure was 4.8%, 4.7%, 0, 12.3%, and 33%, respectively. Body mass index (BMI) and z-BMI score increased significantly as the number of cardiometabolic risk factors increased. Regression analysis revealed that adiponectin (β = −0.501, P = .003) and leptin (β = 0.184, P < .0001) independently predicted the number of MS features. This finding was no longer significant after adjustment for BMI. In the present study, we provide the first estimate of the prevalence of the MS among healthy periadolescents in Greece using the International Diabetes Federation criteria. The MS prevalence was low, with elevated blood pressure being the most dominant feature. Finally, associations with adipokines are mediated by BMI.

Effects of high-fat diet and regular aerobic exercise on global gene expression in skeletal muscle of C57BL/6 mice

Li Fu, Xiaolei Liu, Yanmei Niu, Hairui Yuan, Ning Zhang, Ehud Lavi — 2011-08-05

Abstract: Exercise training may decrease insulin resistance (IR) and increase glucose tolerance. However, the adaptive responses in skeletal muscle at the molecular and genetic level have not been clearly understood. Here we used oligonucleotide microarray analysis to dissect the effects of high-fat diet (HFD) and regular aerobic exercise on global gene expression in the skeletal muscle of C57BL/6 mice. C57BL/6 male mice (n = 40) were fed with normal chow (n = 20) and HFD (n = 20) for 8 weeks. The animals were then divided into 1 of 4 intervention groups: groups of mice fed with normal chow and HFD accompanied with 6-week treadmill running (60 min/d) at 75% maximum oxygen consumption (NE and HE) and their sedentary control groups (NC and HC). Oligonucleotide microarray was applied to analyze the effect of aerobic exercise and HFD at the transcriptional level, and selected genes were confirmed by real-time polymerase chain reaction. Our data showed that 6 weeks of aerobic exercise improved the plasma lipid profile and reversed the glucose intolerance induced by HFD. A set of 503 genes was differentially expressed in samples of HC mice as compared with those of the NC group. Forty of those genes were identified as involved in the process of aerobic exercise ameliorating IR by comparing the changes in expression profiles between the HE and HC groups. These changes include genes involved in metabolism, defense, and inflammation and genes of unknown function. Aerobic exercise training is able to ameliorate IR of mice maintained with HFD. The biochemical pathways involved in ameliorating IR identified in this study may represent potential targets for the treatment of IR.

Acute resistance exercise augments integrative myofibrillar protein synthesis

2011-08-24

Abstract: The purpose of this study was to determine whether an acute bout of high-intensity resistance exercise (RE) would augment integrative mixed muscle and myofibrillar protein fractional synthesis rates (FSRs) when total energy and macronutrient intake was controlled. Twelve healthy young men were studied over 24 hours and performed an acute bout of exhaustive (5 sets until volitional failure of their 85% 1-repetition maximum) unilateral leg press and knee extension exercise, such that one leg was exercised (EX) and the other served as a control (CON). 2H2O (70%) was provided to measure mixed muscle and myofibrillar FSR, and muscle biopsies (vastus lateralis) were collected from the EX and CON legs 16 hours following the RE session. 2H-labeling of body water over the course of the experiment was 0.32 ± 0.01 mole percent excess. Interestingly, integrative mixed muscle FSR (percent per hour) was similar between the CON (0.76% ± 0.08%) and EX (0.69% ± 0.06%) legs. In contrast, upon determination of myofibrillar FSR, there was an RE effect (EX, 0.94% ± 0.16% vs CON, 0.75% ± 0.08%; P < .05). High-intensity RE without prior training impacts integrative myofibrillar 24-hour FSR, perhaps without altering total responses.

S100A16 mediation of weight gain attenuation induced by dietary calcium

2011-08-26

Abstract: Dietary calcium influences the regulation of energy metabolism, and weight gain is attenuated by a high-calcium diet. S100A16 is a novel calcium-binding signaling protein of the EF-hand superfamily that promotes adipogenesis. This study aimed to investigate the effect of S100A16 on weight gain attenuation with a calcium-rich diet. An obese rat model was produced after feeding with a high-fat diet. Animals were randomly divided into 4 groups according to the diet provided over 8 weeks: normal diet group; high-fat, normal-calcium diet group; high-fat, high-calcium diet (HH) group; and high-fat, low-calcium diet group. Serum biochemistry was analyzed, and body weight and visceral fat pads were measured. Expression of S100A16 was assayed by Western blotting. Adipogenesis was detected by oil red O staining. Increases in body weight and visceral fat weight were attenuated in the HH group. High-calcium diets decreased the concentrations of serum total cholesterol and triglyceride. Expression of S100A16 decreased in the HH group. Using the 3T3-L1 preadipocyte model, it was observed that elevation of intracellular Ca2+ via calcium ionophores led to the exclusion of S100A16 from the nucleus. Overexpression of S100A16 in 3T3-L1 preadipocytes enhanced adipogenesis, although a significant reduction in Akt phosphorylation was also detected. High-calcium diets were associated with a significant reduction in body weight gain. High-calcium diets may lead to nuclear exclusion of S100A16, which results in the inhibition of adipogenesis and enhanced insulin sensitivity.

Prophylactic treatment with telmisartan induces tissue-specific gene modulation favoring normal glucose homeostasis in Cohen-Rosenthal diabetic hypertensive rats

Firas Younis, Yoram Oron, Rona Limor, Naftali Stern, Talma Rosenthal — 2011-08-08

Abstract: The objectives were to assess the potential of long-term prophylactic administration of telmisartan, an angiotensin II receptor antagonist and a partial peroxisome proliferator activator receptor (PPAR)γ agonist, in preventing the development of hypertension and hyperglycemia and to demonstrate the alteration in gene expression associated with the development of hyperglycemia and insulin resistance in Cohen-Rosenthal diabetic hypertensive rat, a unique model of hypertension and type 2 diabetes mellitus comorbidity. Cohen-Rosenthal diabetic hypertensive rats were continuously treated with telmisartan (3 mg/[kg d]) starting at age 6 to 8 weeks before developing hypertension or diabetes. Weight changes, blood pressure, blood insulin, adiponectin, glucose tolerance, and insulin sensitivity were monitored. Fat, liver, and muscle messenger RNAs were examined for the expression of genes potentially involved in the onset of insulin resistance. In addition to the expected antihypertensive effect of prophylactic telmisartan, diabetes was blunted, evidenced at the end of the study by a significantly lower glucose level. This was accompanied by improved glucose tolerance, increased sensitivity to insulin, reduction in fasting insulin levels and homeostasis model assessment index, as well as an increase in serum adiponectin. Telmisartan also prevented the increase in serum triglycerides and the associated appearance of lipid droplets in the liver. Diabetes induced tissue-specific changes in messenger RNAs expression of the following selected genes, which were restored by telmisartan treatment: PPARγ, PPARδ, PPARγ coactivator 1α, adiponectin, adiponectin receptor 1, adiponectin receptor 2, phosphotyrosine binding domain and a pleckstrin homology domain-containing adaptor protein, adenosine monophosphate kinase, and glucose translocator 4. Telmisartan blunted the development of hypertension, insulin resistance, and diabetes in prediabetic Cohen-Rosenthal diabetic hypertensive rats through pleiotropic activity, involving specific gene regulation of target organs.

Mitochondrial regulators of fatty acid metabolism reflect metabolic dysfunction in type 2 diabetes mellitus

2011-08-04

Abstract: The delicate homeostatic balance between glucose and fatty acid metabolism in relation to whole-body energy regulation is influenced by mitochondrial function. We determined expression and regulation of mitochondrial enzymes including pyruvate dehydrogenase kinase (PDK) 4, PDK2, carnitine palmitoyltransferase 1b, and malonyl–coenzyme A decarboxylase in skeletal muscle from people with normal glucose tolerance (NGT) or type 2 diabetes mellitus (T2DM). Vastus lateralis biopsies were obtained from NGT (n = 79) or T2DM (n = 33) men and women matched for age and body mass index. A subset of participants participated in a 4-month lifestyle intervention program consisting of an unsupervised walking exercise. Muscle biopsies were analyzed for expression and DNA methylation status. Primary myotubes were derived from biopsies obtained from NGT individuals for metabolic studies. Cultured skeletal muscle was exposed to agents mimicking exercise activation for messenger RNA (mRNA) expression analysis. The mRNA expression of PDK4, PDK2, and malonyl–coenzyme A decarboxylase was increased in skeletal muscle from T2DM patients. Methylation of the PDK4 promoter was reduced in T2DM and inversely correlated with PDK4 expression. Moreover, PDK4 expression was positively correlated with body mass index, blood glucose, insulin, C peptide, and hemoglobin A1c. A lifestyle intervention program resulted in increased PDK4 mRNA expression in NGT individuals, but not in those with T2DM. Exposure to caffeine or palmitate increased PDK4 mRNA in a cultured skeletal muscle system. Our findings reveal that skeletal muscle expression of PDK4 and related genes regulating mitochondrial function reflects alterations in substrate utilization and clinical features associated with T2DM. Furthermore, hypomethylation of the PDK4 promoter in T2DM coincided with an impaired response of PDK4 mRNA after exercise.

Association between the severity of obstructive sleep apnea and the ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol

Yoshiyuki Kawano, Akira Tamura, Junichi Kadota — 2011-08-05

Abstract: The positive association between the ratio of serum low-density lipoprotein cholesterol (LDL-C) to serum high-density lipoprotein cholesterol (HDL-C) and cardiovascular events has recently been receiving much attention. However, the association between the severity of obstructive sleep apnea (OSA) and this ratio has not yet been investigated. Accordingly, we sought to clarify this association and the effect of continuous positive airway pressure (CPAP) therapy on the ratio. We performed polysomnography and LDL-C/HDL-C measurements in 215 patients who were suspected of having OSA. Furthermore, LDL-C/HDL-C was again evaluated 6 months after polysomnography in 30 OSA patients for whom CPAP therapy was initiated and continued, and in 11 age- and sex-matched OSA patients for whom the therapy could not be initiated. The LDL-C/HDL-C correlated positively with apnea-hypopnea index (ρ = 0.28, P < .001) and negatively with the lowest arterial oxyhemoglobin saturation (ρ = −0.30, P < .001). Multivariate regression analysis revealed that ln apnea-hypopnea index (or ln lowest arterial oxyhemoglobin saturation) was independently associated with LDL-C/HDL-C. The LDL-C/HDL-C decreased after 6 months in the CPAP group (2.29 ± 0.67 to 2.11 ± 0.74, P = .02), whereas it did not change in the non-CPAP group (2.65 ± 0.82 to 2.62 ± 0.66, P = .81). The severity of OSA was independently associated with LDL-C/HDL-C, and LDL-C/HDL-C was significantly reduced at 6 months after CPAP therapy. These findings suggest that LDL-C/HDL-C increases in proportion to the severity of OSA, which may contribute partly to an increased risk for cardiovascular events in OSA patients.

Circulating androgen levels are associated with subclinical atherosclerosis and arterial stiffness in healthy recently menopausal women

2011-08-05

Abstract: Although increasing evidence supports an association between endogenous sex hormones and cardiovascular disease, the results still remain controversial. This study aims to examine the association between endogenous sex hormones and indices of vascular function and structure. Serum follicle-stimulating hormone, luteinizing hormone, estradiol, testosterone, sex hormone–binding globulin, dehydroepiandrosterone sulfate (DHEAS), and Δ4-androstenedione were measured in 120 healthy postmenopausal women aged 41 to 60 years. Possible associations with surrogate markers of subclinical atherosclerosis, arterial stiffness, and endothelial function were investigated. Indices of arterial structure included carotid and femoral intima-media thickness and atheromatous plaques presence. Indices of arterial function included flow-mediated dilation of the brachial artery, carotid-femoral pulse wave velocity (PWV), and augmentation index. Total testosterone and free androgen index (FAI) were the most important predictors of common carotid artery intima-media thickness (β = 0.376 and β = 0.236, P < .001 and P = .014, respectively). Similarly, FAI was the only significant independent predictor of PWV (β = 0.254, P = .027) after adjusting for age, smoking, body mass index, homeostasis model assessment of insulin resistance, and blood lipids. Free estrogen index showed a positive association with PWV, independently of age, smoking, and body mass index, but not of homeostasis model assessment of insulin resistance and blood lipids. Age-adjusted levels of DHEAS exhibited a significant independent negative association with measures of augmentation index. Follicle-stimulating hormone, luteinizing hormone, estradiol, sex hormone–binding globulin, and Δ4-androstenedione were not associated with any of the vascular parameters independently of traditional cardiovascular risk factors. Higher serum testosterone and FAI are associated with subclinical atherosclerosis in healthy recently menopausal women. This association is independent of traditional cardiovascular risk factors or insulin resistance. On the contrary, serum DHEAS exhibits a negative association with arterial stiffness.

Postprandial changes in plasma acylcarnitine concentrations as markers of fatty acid flux in overweight and obesity

Maria A. Ramos-Roman, Lawrence Sweetman, Maressa J. Valdez, Elizabeth J. Parks — 2011-08-08

Abstract: This study determined whether reductions in postprandial plasma nonesterified fatty acid (FFA) flux would lead to reductions in plasma acylcarnitine (AC) concentrations. Plasma AC was measured by liquid chromatography with tandem mass spectrometry in the fasting state and over 6 hours after a high-fat (50% energy) meal was fed to 16 overweight and obese subjects with a wide range of insulin sensitivities. Body composition was measured by dual-energy x-ray absorptiometry; insulin sensitivity by insulin-modified, frequently sampled intravenous glucose tolerance test; substrate oxidation by indirect calorimetry; blood metabolite and hormone concentrations biochemically; and fatty acid flux by using stable isotope tracers. Lean body mass and fasting fat oxidation correlated positively (r > 0.522, P < .05), whereas glucose oxidation correlated negatively (r < −0.551, P < .04), with fasting AC. Postprandially, plasma glucose, insulin, and triglyceride concentrations increased; and FFA concentrations decreased significantly. The responses of plasma AC species depended on chain length and saturation, with C14:0, C16:0, and C18:0 remaining unchanged, and unsaturated species (eg, C14:1, C14:2) falling significantly (21%-46%, P < .03). Postmeal nadir AC concentrations were positively associated with lean body mass, postprandial fatty acid flux, and FFA concentrations (r > 0.515, P < .05). By contrast, nadir AC correlated negatively with insulin sensitivity and spillover of meal-derived fatty acids (r < −0.528, P < .04). Conditions that impact fatty acid flux contribute to the control of postprandial plasma AC concentrations. These data underscore the need for a better understanding of postprandial fatty acid oxidation and dietary fat delivery in the setting of adipose insulin resistance to determine how postprandial lipemia contributes to chronic disease risk.

Fatness, fitness, and cardiometabolic risk factors in middle-aged white men

Gary O'Donovan, Edward Kearney, Roy Sherwood, Melvyn Hillsdon — 2011-08-05

Abstract: The objective was to test the hypothesis that traditional and novel cardiometabolic risk factors would be significantly different in groups of men of different fatness and fitness. Total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, insulin, high-sensitivity C-reactive protein, alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, leptin, adiponectin, tumor necrosis factor–α, interleukin-6, interleukin-10, fibrinogen, and insulin resistance were assessed in 183 nonsmoking white men aged 35 to 53 years, including 62 who were slim and fit (waist girth ≤90 cm and maximal oxygen consumption [VO2max] above average), 24 who were slim and unfit (waist girth ≤90 cm and VO2max average or below), 39 who were fat and fit (waist girth ≥100 cm and VO2max above average), and 19 who were fat and unfit (waist girth ≥100 cm and VO2max average or below). Seventy-six percent gave blood on 2 occasions, and the average of 1 or 2 blood tests was used in statistical tests. Waist girth (centimeters) and fitness (milliliters of oxygen per kilogram of fat-free mass) were associated with high-density lipoprotein cholesterol, leptin, and insulin resistance after adjustment for age, saturated fat intake, and total energy intake. High-density lipoprotein cholesterol, triglycerides, alanine aminotransferase, and insulin resistance were significantly different in men who were fat and fit and those who were fat and unfit. These data suggest that differences in lipid and lipoprotein concentrations, liver function, and insulin resistance may explain why the risks of chronic disease are lower in men who are fat and fit than those who are fat and unfit.

Combined hypertriglyceridemic and insulin-glucose clamps for the characterization of substrate oxidation and plasma elimination of a long-chain triglyceride emulsion in healthy men

Viveca Åberg, Anders Thörne, Anders Alvestrand, Jörgen Nordenström — 2011-08-24

Abstract: This study examines the effect of glucose and insulin on the plasma elimination rate and oxidation of a fat emulsion by using indirect calorimetry in conjunction with lipid and insulin-glucose clamp techniques. Ten healthy subjects were studied on 2 occasions in a randomized, open, crossover study. On one occasion, a hypertriglyceridemic (HTG) clamp was administrated alone; and, on the other, HTG and insulin-glucose (IG) clamps were administrated simultaneously. During HTG clamps, serum triglyceride (TG) concentration was maintained at 4 mmol × L−1. During the IG clamp, insulin was administered at a rate of 20 mU × m−2 × min−1; and the glucose level was maintained at 7 mmol × L−1. Continuous indirect calorimetry was carried out throughout the study period. The infusion rate required to maintain stable serum TG concentrations did not differ between the 2 clamps. Mean free fatty acid concentration was lower during the HTG/IG than during the HTG clamp (0.40 ± 0.04 vs 0.82 ± 0.07 mmol × L−1; P < .001). However, the increases in β-OH-butyrate levels were significantly lower in the HTG/IG compared with the HTG clamp (0.09 ± 0.04 vs 0.55 ± 0.09 mmol × L−1; P < .001). Energy expenditure and the respiratory quotient were significantly higher at steady state in the HTG/IG than in the HTG clamp: 1.47 ± 0.06 vs 1.34 ± 0.04 kcal × min−1 (P < .01) and 0.85 ± 0.01 vs 0.79 ± 0.01 (P < .01), respectively. Insulin and glucose did not significantly change plasma TG disposal rate (P = .0987) or total lipid oxidation (P = .3204) in this metabolic situation with an abundant supply of both carbohydrates and lipids. β-OH-butyrate increased during both clamps, indicating an ongoing hepatic fatty oxidation despite the administration of glucose/insulin.

Acute hypoglycemia causes depressive-like behaviors in mice

Min Jung Park, Samuel W. Yoo, Brian S. Choe, Robert Dantzer, Gregory G. Freund — 2011-08-05

Abstract: Reports in humans advocate a link between hypoglycemia and altered mood. Such observations, however, have not been mechanistically explored. Here we examined depressive-like behaviors in mice resulting from acute hypoglycemia. Mice were fasted for 12 hours and then administered intraperitoneal insulin to induce a blood glucose nadir of 50 mg/dL at 0.75 hour after injection that by 2 hours postinjection had returned to normal. The behaviors of locomotion, forced swim, saccharin preference, and novel object recognition were subsequently examined. Mice made hypoglycemic showed depressive-like behaviors 24 hours after resolution of hypoglycemia as evidenced by increased immobility in the forced swim test (FST) and reduced saccharin preference. Movement and memory were not impacted by hypoglycemia 24 hours after its resolution. By 48 hours posthypoglycemia, depressive-like behaviors resolved. In contrast, neither peripheral insulin administration without resultant hypoglycemia nor intracerebroventricular insulin administration altered performance in the FST. The antidepressants fluoxetine and desipramine prevented hypoglycemia-induced immobility in the FST, as did the antiadrenergic agents phentolamine, metoprolol, and butoxamine. Epinephrine and norepinephrine administration caused increased immobility in the FST at 24 hours postadministration that subsequently resolved by 48 hours. These data indicate that, in mice, acute hypoglycemia through adrenergic pathways caused depressive-like behaviors that exist well beyond the resolution of hypoglycemia.

Influence of resting energy expenditure on blood pressure is independent of body mass and a marker of sympathetic tone

David W. Brock, Connie L. Tompkins, Gordon Fisher, Gary R. Hunter — 2011-08-05

Abstract: Two recent examinations reported a strong association between blood pressure (BP) and resting energy expenditure (REE), independent of body mass and body composition. Both reports postulate that neurohumoral processes that contribute to variation in REE may partly mediate the body mass effect on BP. Therefore, we examined the relationship of REE and BP in 108 asymptomatic women (a) to confirm previous findings in a novel population and (b) to examine the impact of a marker of sympathetic tone on this relationship, as this was indicated as a potentially salient intermediary in previous reports. All testing was performed during a 4-day admission to the General Clinical Research Center. Resting energy expenditure was measured by indirect calorimetry, body composition was determined by dual-energy x-ray absorptiometry, and 24-hour fractionated urinary norepinephrine was determined by high-performance liquid chromatography. Multiple linear regression revealed REE as a significant predictor of systolic BP (β = 0.30, P = .04), independent of race (β = 0. 28, P = .01), age (β = −0.02, P = .80), height (β = −0.38, P = .08), fat mass (β = 0.22, P = .20), fat-free mass (β = 0.08, P = .65), and 24-hour fractionated urinary norepinephrine (β = 0.06, P = .57); and the same model using diastolic BP as the dependent variable approached significance (β = 0.24, P = .09). This study affirms previous findings that REE may be a potential mediator in resting BP, independent of many well-cited factors and, additionally, a marker of sympathetic tone.

The association of diabetes mellitus with liver, colon, lung, and prostate cancer is independent of hypertension, hyperlipidemia, and gout in Taiwanese patients

Mei-Yueh Lee, Kun-Der Lin, Pi-Jung Hsiao, Shyi-Jang Shin — 2011-08-05

Abstract: Studies have shown an association between diabetes and cancer in Western countries; but this, as well as the influence of associated metabolic factors, must be confirmed by a prospective study in other population groups. This study aimed to investigate whether the strong association of cancer and diabetes is independent from the influence of hypertension, dyslipidemia, and gout in the Taiwanese population. A total of 985 815 study subjects were identified from the National Health Insurance in 1997 and followed up from 1998 to 2009. The demographic characteristics between patients with diabetes and cancer, including age, sex, hypertension, dyslipidemia, and gout, were analyzed using the χ2 test. Cox proportional hazard regression models were used to determine the independent effects of diabetes on the risks of cancer. A total of 104 343 diabetic patients were followed up from 1998 to 2009. After adjusting for sex, age, hypertension, dyslipidemia, and gout, the incidences of cancer at any site and in the liver, colon, lungs, and prostate in diabetic patients were independently higher, with risk ratios of 1.56 (95% confidence interval [CI], 1.43-1.71), 1.67 (95% CI, 1.39-2.01), 1.75 (95% CI, 1.49-2.06), 1.54 (95% CI, 1.26-1.88), and 1.56 (95% CI, 1.19-2.04), respectively. Only breast cancer did not show any clinical significance. There was an increased incidence of cancer at any site in the diabetic patients compared with nondiabetic subjects. The most common cancers were liver, colon, lung, breast, and prostate cancer; and except for breast cancer, their incidences increased independently of hypertension, dyslipidemia, and gout in patients with diabetes.

Sources of hepatic glycogen synthesis following a milk-containing breakfast meal in healthy subjects

2011-08-22

Abstract: During feeding, dietary galactose is a potential source of hepatic glycogen synthesis; but its contribution has not been measured to date. In the presence of deuterated water (2H2O), uridine diphosphate (UDP)–glucose derived from galactose is not enriched, whereas the remainder derived from glucose-6-phosphate (G6P) is enriched in position 2 to the same level as body water, assuming complete G6P–fructose-6-phosphate (F6P) exchange. Hence, the difference between UDP-glucose position 2 and body water enrichments reflects the contribution of galactose to glycogen synthesis relative to all other sources. In study 1, G6P-F6P exchange in 6 healthy subjects was quantified by supplementing a milk-containing breakfast meal with 10 g of [U-2H7]glucose and quantifying the depletion of position 2 enrichment in urinary menthol glucuronide. In study 2, another 6 subjects ingested 2H2O and acetaminophen followed by an identical breakfast meal with 10 g of [1-13C]glucose to resolve direct/indirect pathways and galactose contributions to glycogen synthesis. Metabolite enrichments were determined by 2H and 13C nuclear magnetic resonance. In study 1, G6P-F6P exchange approached completion; therefore, the difference between position 2 and body water enrichments in study 2 (0.20% ± 0.03% vs 0.27% ± 0.03%, P < .005) was attributed to galactose glycogenesis. Dietary galactose contributed 19% ± 3% to glycogen synthesis. Of the remainder, 58% ± 5% was derived from the direct pathway and 22% ± 4% via the indirect pathway. The contribution of galactose to hepatic glycogen synthesis was resolved from that of direct and indirect pathways using a combination of 2H2O and [1-13C]glucose tracers.

Salivary cortisol levels are associated with outcomes of weight reduction therapy in obese Japanese patients

2011-08-26

Abstract: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis can increase the risk of cardiovascular disease (CVD). However, the detailed relationships of HPA axis activity with weight reduction and CVD risk factors in obese patients have not been examined. This study was designed to elucidate the associations of salivary cortisol levels with weight reduction and CVD risk factors in obese patients. As a marker of HPA axis activity, we measured the morning salivary cortisol levels of 83 obese Japanese outpatients. We also examined metabolic parameters, inflammatory markers, and indicators of arterial stiffness, that is, the pulse wave velocity and cardio-ankle vascular index. All 83 obese patients underwent 3-month weight reduction therapy with lifestyle modification. At the baseline, multivariate regression analysis revealed that only logarithmic transformation of C-reactive protein (β = 0.258, P < .05) and cardio-ankle vascular index (β = 0.233, P < .05) were independent determinants of the salivary cortisol levels. However, other metabolic parameters were not significantly associated with the salivary cortisol levels. In addition, lower salivary cortisol levels and higher body weight at the baseline were the only independent determinants of successful weight loss through the weight reduction therapy (P < .01). The present study demonstrates that the baseline morning salivary cortisol levels are significantly associated with the levels of an inflammatory marker, arterial stiffness, and successful weight reduction in obese patients. Therefore, salivary cortisol could be a useful marker for assessing and managing body weight and CVD risk factors in obese patients.

Improvement in insulin sensitivity following a 1-year lifestyle intervention program in viscerally obese men: contribution of abdominal adiposity

2011-08-24

Abstract: The objectives of the study were to quantify the effect of a 1-year healthy eating–physical activity/exercise lifestyle modification program on insulin sensitivity in viscerally obese men classified according to their glucose tolerance status and to evaluate the respective contributions of changes in body fat distribution vs changes in cardiorespiratory fitness (CRF) to the improvements in indices of plasma glucose/insulin homeostasis. Abdominally obese, dyslipidemic men (waist circumference ≥90 cm, triglycerides ≥1.69 mmol/L, and/or high-density lipoprotein cholesterol <1.03 mmol/L) were recruited. The 1-year intervention/evaluation was completed by 104 men. Body weight, composition, and fat distribution were assessed by dual-energy x-ray absorptiometry/computed tomography. Cardiorespiratory fitness and cardiometabolic risk profile were measured. After 1 year, insulin sensitivity improved in association with decreases in both visceral (VAT) and subcutaneous adiposity (SAT) as well as with the improvement in CRF, regardless of baseline glucose tolerance. Further analyses were performed according to changes in glucose tolerance status: improvement (group I, n = 39), no change (group N, n = 50), or worsening (group W, n = 15) after 1 year. Groups I and N improved their insulin sensitivity and their CRF, whereas group W did not, while losing less VAT than groups I and N. Multiple regressions showed that reduction in VAT was associated with an improvement in homeostasis model assessment of insulin resistance, whereas reduction in SAT was rather associated with improvement of the insulin sensitivity index of Matsuda. Changes in CRF were not independently associated with changes in indices of plasma glucose/insulin homeostasis. A 1-year lifestyle intervention improved plasma glucose/insulin homeostasis in viscerally obese men, including those with normal glucose tolerance status at baseline. Changes in SAT and VAT but not in CRF appeared to mediate these improvements.

Effect of exercise training combined with phytoestrogens on adipokines and C-reactive protein in postmenopausal women: a randomized trial

2011-08-24

Abstract: Phytoestrogens and training could be effective to reduce cardiovascular and type 2 diabetes mellitus risk factors in postmenopausal women. Nevertheless, the impact of their combination on adipokines and systemic inflammation was never investigated. The objective was to verify if 6 months of mixed training combined with phytoestrogens could have an additional effect on adipokine levels and systemic inflammation in obese postmenopausal women. Fifty-two obese women aged between 50 and 70 years were randomly assigned to (1) exercise with placebo (EX + PL; n = 25) or (2) exercise with phytoestrogens (EX + PHY; n = 27). Body weight, waist circumference, fat mass, and lean body mass (dual-energy x-ray absorptiometry) were assessed. Fasting plasma glucose and insulin, adiponectin, leptin, and C-reactive protein (CRP) levels were obtained after a 12-hour overnight fast. Total energy intake was measured with a 3-day dietary record. All measurements were performed before and after the 6-month intervention. Although energy intake remained unchanged, body composition was improved in all women (all Ps < .02). Plasma CRP and leptin levels decreased in both groups similarly (all Ps < .03), whereas plasma adiponectin and insulin did not change with exercise combined with placebo or phytoestrogens. Correlation analyses showed that homeostasis model assessment of insulin resistance (r = −0.58, P = .02) and fasting insulin levels (r = −0.42, P = .02) at baseline were both correlated with changes in leptin levels. Baseline fasting glucose (r = −0.36, P = .03) and adiponectin (r = 0.45, P = .005) levels were associated with changes in CRP concentrations. Although mixed exercise program combined with phytoestrogens does not seem to provide any additional effect, mixed training improves systemic inflammation and leptin concentrations in obese postmenopausal women.

High serum uric acid level and low urine pH as predictors of metabolic syndrome: a retrospective cohort study in a Japanese urban population

2011-08-24

Abstract: The objective of this study was to evaluate whether hyperuricemia, acidic urine, or their combination predicts metabolic syndrome (MetS). In study 1, 69 094 subjects who received a general health checkup between 1985 and 2005 were included in a cross-sectional study of serum uric acid (SUA) and urine pH in relation to MetS. In study 2, the association of SUA and urine pH with MetS development over a 5-year period was evaluated in 5617 subjects with body mass index less than 25 kg/m2 at the first examination. In study 1, higher SUA and lower urine pH were both positively correlated to MetS status (P < .001). The combination of high SUA and low urine pH was significantly associated with higher MetS prevalence compared with the combination of low SUA and high urine pH (odds ratio, 3.383; 95% confidence interval [CI], 3.034-3.784 in men; odds ratio, 4.000; 95% CI, 2.992-5.452 in women). In study 2, the top quartile of SUA levels was associated with higher MetS development compared with the bottom quartile during the 5-year period in men (hazard ratio [HR], 1.793; 95% CI, 1.084-2.966; P = .023). In women, the HR was 3.732 (95% CI, 0.391-35.62; P = .252) for the upper vs the lower half of SUA levels. For urine pH, the HR was 1.955 (95% CI, 1.089-3.509; P = .025) for the bottom vs the top quartile in men. A likelihood ratio test confirmed that high SUA and low urine pH act synergistically in the development of MetS. High SUA, low urine pH, and their combination are predictive risk factors for MetS development.

2012-02-01

Editorial Board

2012-02-01

Metabolism - Clinical and Experimental

Masthead

Dietary calcium and body weight: what's the “skinny”?

Metabolic syndrome in a Mediterranean pediatric cohort: prevalence using International Diabetes Federation–derived criteria and associations with adiponectin and leptin

Effects of high-fat diet and regular aerobic exercise on global gene expression in skeletal muscle of C57BL/6 mice

Acute resistance exercise augments integrative myofibrillar protein synthesis

S100A16 mediation of weight gain attenuation induced by dietary calcium

Prophylactic treatment with telmisartan induces tissue-specific gene modulation favoring normal glucose homeostasis in Cohen-Rosenthal diabetic hypertensive rats

Mitochondrial regulators of fatty acid metabolism reflect metabolic dysfunction in type 2 diabetes mellitus

Association between the severity of obstructive sleep apnea and the ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol

Circulating androgen levels are associated with subclinical atherosclerosis and arterial stiffness in healthy recently menopausal women

Postprandial changes in plasma acylcarnitine concentrations as markers of fatty acid flux in overweight and obesity

Fatness, fitness, and cardiometabolic risk factors in middle-aged white men

Combined hypertriglyceridemic and insulin-glucose clamps for the characterization of substrate oxidation and plasma elimination of a long-chain triglyceride emulsion in healthy men

Acute hypoglycemia causes depressive-like behaviors in mice

Influence of resting energy expenditure on blood pressure is independent of body mass and a marker of sympathetic tone

The association of diabetes mellitus with liver, colon, lung, and prostate cancer is independent of hypertension, hyperlipidemia, and gout in Taiwanese patients

Sources of hepatic glycogen synthesis following a milk-containing breakfast meal in healthy subjects

Salivary cortisol levels are associated with outcomes of weight reduction therapy in obese Japanese patients

Improvement in insulin sensitivity following a 1-year lifestyle intervention program in viscerally obese men: contribution of abdominal adiposity

Effect of exercise training combined with phytoestrogens on adipokines and C-reactive protein in postmenopausal women: a randomized trial

High serum uric acid level and low urine pH as predictors of metabolic syndrome: a retrospective cohort study in a Japanese urban population

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