Metabolism - Clinical and Experimental RSS feed: Current Issue. This eminent journal is regarded by clinicians and researchers alike as an authoritative source of practical information on metabolic processes and diseases in the areas of nutrition, genetics, dystrophies, diabetes and gout. Reviews and surveys on the status of research and practice in specific metabolic disorders are featured.http://www.metabolismjournal.com/?rss=yesElsevier Inc.en © 2010 Published by Elsevier Inc. All rights reserved. Metabolism - Clinical and Experimental0026-0495598August 2010 © 2010 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.metabolismjournal.com/article/PIIS0026049510001903/abstract?rss=yesMasthead10.1016/S0026-0495(10)00190-3Metabolism - Clinical and Experimental 59, 8 (2010)2010-08-01Metabolism - Clinical and Experimental2010-08-01598S0026-0495(10)X0007-5IFCIFChttp://www.metabolismjournal.com/article/PIIS0026049510002179/abstract?rss=yesSummer 2010 marks the end of an era: the retirement after 40 years of Editor-in-Chief Dr James B. Field. This service surely ranks as one of the longest and most steadfast of any medical journal editor; and as the latest in a long line of his publishers, I would like to thank him for his commitment to Metabolism, its authors, and its readers. Sic transit gloria mundi. We plan soon to announce his successor.Tributes to retiring Editor-in-Chief of Metabolism, James B. Field10.1016/j.metabol.2010.07.002Metabolism - Clinical and Experimental 59, 8 (2010)2010-08-01Metabolism - Clinical and Experimental2010-08-01598S0026-0495(10)X0007-510831083http://www.metabolismjournal.com/article/PIIS0026049509004752/abstract?rss=yesAbstract: Insulin-induced gene 2 (INSIG2) plays an important role in the regulation of cholesterol and fatty acids synthesis. A polymorphism, rs7566605, located 10 kilobases upstream of the INSIG2 gene, was identified in a genomewide association study of obesity. We conducted an association study of 12 INSIG2 tag–single nucleotide polymorphisms with longitudinal measures of body size (body mass index and waist circumference) and lipid metabolism (plasma high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides levels). We investigated their interaction with age in 4304 Coronary Artery Risk Development in Young Adults participants (49.5% blacks, 50.5% whites) followed prospectively for 20 years. rs7566605 was not associated with variation in body size or lipid metabolism at any age in either racial group. However, rs1352083 and rs10185316 were associated with age-related decline in high-density lipoprotein cholesterol in whites (P = .0005 and .04, respectively). A similar trend was observed in blacks who consistently maintained a body mass index less than 25 kg/m2 over the study period. These data support a role of INSIG2 sequence variation in the regulation of cholesterol metabolism.Common INSIG2 polymorphisms are associated with age-related changes in body size and high-density lipoprotein cholesterol from young adulthood to middle ageMyriam Fornage, George Papanicolaou, Cora E. Lewis, Eric Boerwinkle, David S. Siscovick10.1016/j.metabol.2009.11.005Metabolism - Clinical and Experimental 59, 8 (2010)2010-01-04Metabolism - Clinical and Experimental2010-01-04598S0026-0495(10)X0007-510841091http://www.metabolismjournal.com/article/PIIS0026049509004764/abstract?rss=yesAbstract: Nonalcoholic fatty liver disease results from overconsumption and is a significant and increasing cause of liver failure. The type of diet that is conducive to the development of this disease has not been established, and evidence-based treatment options are currently lacking. We hypothesized that the onset of hepatic steatosis is linked to the consumption of a diet with a high fat content, rather than related to excess caloric intake. In addition, we also hypothesized that fully manifested hepatic steatosis could be reversed by reducing the fat percentage in the diet of obese mice. C57BL/6J male mice were fed either a purified rodent diet containing 10% fat or a diet with 60% of calories derived from fat. A pair-feeding design was used to distinguish the effects of dietary fat content and caloric intake on dietary-induced hepatic lipid accumulation and associated injury. Livers were analyzed by quantitative reverse transcriptase polymerase chain reaction for lipid metabolism-related gene expression. After 9 weeks, mice on the 60%-fat diet exhibited more weight gain, insulin resistance, and hepatic steatosis compared with mice on a 10%-fat diet with equal caloric intake. Furthermore, mice with established metabolic syndrome at 9 weeks showed reversal of hepatic steatosis, insulin resistance, and obesity when switched to a 10%-fat diet for an additional 9 weeks, independent of caloric intake. Quantitative reverse transcriptase polymerase chain reaction revealed that transcripts related to both de novo lipogenesis and increased uptake of free fatty acids were significantly up-regulated in mice pair-fed a 60%-fat diet compared with 10%-fat–fed animals. Dietary fat content, independent from caloric intake, is a crucial factor in the development of hepatic steatosis, obesity, and insulin resistance in the C57BL/6J diet-induced obesity model caused by increased uptake of free fatty acids and de novo lipogenesis. In addition, once established, all these features of the metabolic syndrome can be successfully reversed after switching obese mice to a diet low in fat. Low-fat diets deserve attention in the investigation of a potential treatment of patients with nonalcoholic fatty liver disease.Dietary fat intake promotes the development of hepatic steatosis independently from excess caloric consumption in a murine modelVincent E. de Meijer, Hau D. Le, Jonathan A. Meisel, M. Reza Akhavan Sharif, Amy Pan, Vânia Nosé, Mark Puder10.1016/j.metabol.2009.11.006Metabolism - Clinical and Experimental 59, 8 (2010)2010-01-08Metabolism - Clinical and Experimental2010-01-08598S0026-0495(10)X0007-510921105http://www.metabolismjournal.com/article/PIIS0026049509004776/abstract?rss=yesAbstract: Mutations in the lamin A/C gene (LMNA) cause lipodystrophy. However, little data are available on lamin A/C expression in various fat depots in women. We recruited 34 women scheduled for gynecologic surgery. Blood samples were collected on the morning of surgery to obtain a detailed lipid profile. Radiological examinations were performed to measure total body fat mass and abdominal fat accumulation. Fat samples were taken from the subcutaneous (SC) fat depot and from the greater omentum (OM) during the surgical procedure. Whole adipose tissue samples were used for total messenger RNA (mRNA) extraction and real-time polymerase chain reaction quantification of the LMNA transcript. No association was observed between lamin A/C mRNA expression, either in SC or OM fat tissue, and adiposity measures. Women with low SC lamin A/C expression, identified on the basis of the median value of SC lamin A/C mRNA expression, had a significantly altered lipid profile including lower levels of high-density lipoprotein (HDL) cholesterol and HDL2 cholesterol and reduced HDL2 cholesterol to HDL3 cholesterol ratio (P < .05 for all). These women were also characterized by higher cholesterol to HDL cholesterol, low-density lipoprotein–triglycerides, very low-density lipoprotein–apolipoprotein B, and low-density lipoprotein cholesterol to HDL cholesterol (P < .05 for all). Low SC lamin A/C mRNA expression levels were also associated with significantly increased lipolysis in isolated fat cells from this fat depot. Specifically, the response to lipolytic agent isoproterenol was significantly increased at doses ranging from 10−5 to 10−10 mol/L (P < .05). A similar trend was observed in OM fat cells but did not reach significance. In conclusion, low lamin A/C expression in SC adipose tissue is associated with significant alterations in the lipid profile and increased fat cell lipolysis, independent of the level of total or abdominal adiposity.Adipose tissue lamin A/C messenger RNA expression in womenMélanie Nadeau, Suzanne Noël, Philippe Y. Laberge, Johanne Hurtubise, André Tchernof10.1016/j.metabol.2009.09.034Metabolism - Clinical and Experimental 59, 8 (2010)2010-01-04Metabolism - Clinical and Experimental2010-01-04598S0026-0495(10)X0007-511061114http://www.metabolismjournal.com/article/PIIS0026049509004788/abstract?rss=yesAbstract: Metabolic syndrome (MetS) as defined by the Adult Treatment Panel (ATP) III criteria includes 3 metabolic parameters: serum glucose, triglycerides, and high-density lipoprotein cholesterol (HDL-C) measurements. However, the impact of each of the 3 metabolic parameters on cardiovascular disease (CVD) risk in African American women (AAW) is unknown. Therefore, we investigated CVD risk clusters associated with each of the 3 metabolic components of MetS in adult nondiabetic, overweight/obese AAW. We studied the clinical and metabolic CVD risk factors of 258 AAW (mean age, 42.4 ± 8.4 years; mean body mass index, 33.4 ± 8.0 (kg/m2). Fasting serum insulin, glucose, and C-peptide levels were obtained in each subject. Waist circumference and systolic and diastolic blood pressure were measured. Insulin sensitivity (Bergman minimal model method) and insulin resistance (homeostasis model assessment) were calculated. We examined the prevalence of MetS and its components associated with each of the 3 metabolic components (ie, serum glucose, HDL-C, and triglycerides) of the MetS as defined by ATP III. Worsening of any of the 3 metabolic parameters was associated with increasing waist circumference but not with age and body mass index nor with insulin, C-peptide, homeostasis model assessment of insulin resistance, and insulin sensitivity. As a group, the prevalence of MetS was 35.5% in our AAW. The prevalence of MetS increased 3-fold from first to third tertiles of serum glucose (14.1% and 42.3%, respectively). Worsening of serum HDL-C from tertiles 3 to 1 was associated with significant increases in the prevalence of MetS (1.2% vs 42.3%, respectively). Comparing first with third tertile of triglycerides, there was no significant increase in MetS in our AAW (7% vs 17%). Contrasting the 3 metabolic components, the prevalence of MetS was higher in the third tertile of glucose (43.2%) and first tertile of HDL-C (42.3%) and least with the third tertile of triglycerides (17%). In summary, each of the metabolic components of MetS was associated with different degrees of the clustering of CVD risk factors in AAW. We found that alterations in serum glucose and HDL-C were more predictive of MetS, each yielding approximately 40% of the prevalence of MetS in our nondiabetic, obese AAW. We found that triglycerides had the least impact on MetS in our AAW. We propose (1) that the 3 metabolic parameters for MetS defined by ATP III should be weighted differently with respect to their potential for CVD risks and perhaps outcomes and (2) that nondiabetic AAW in our third tertile of serum glucose (>100 mg/dL) and/or first tertile of HDL-C (<40 mg/dL) should be targeted for screening for MetS.Differential impact of serum glucose, triglycerides, and high-density lipoprotein cholesterol on cardiovascular risk factor burden in nondiabetic, obese African American women: implications for the prevalence of metabolic syndromeTrudy Gaillard, Dara Schuster, Kwame Osei10.1016/j.metabol.2009.09.035Metabolism - Clinical and Experimental 59, 8 (2010)2010-01-06Metabolism - Clinical and Experimental2010-01-06598S0026-0495(10)X0007-511151123http://www.metabolismjournal.com/article/PIIS002604950900479X/abstract?rss=yesAbstract: Early diagnostics of cobalamin (Cbl, vitamin B12) deficiency is primarily based on measurements of the relevant metabolic markers in blood plasma—total B12, specific Cbl-saturated transporter holo-transcobalamin (holoTC), and substrates of Cbl-dependent enzymatic reactions methylmalonic acid (MMA) and homocysteine (Hcy). Concentrations of B12 and holoTC decrease whereas MMA and Hcy increase under deficiency. Yet, the results of individual tests are often contradictory and do not guarantee unambiguous diagnosis. The current work describes the metabolic manifestation of vitamin B12 deficiency in terms of flux equations fitted to data sets from literature. The model mathematically connects all the markers and presents 4 independent measurements as a single point (x, y) in the combined coordinates x = (holoTC·B12)½ and y = ½log10(MMA·Hcy). Pairwise averaging compensates for the individual fluctuations of the markers caused by (1) irregular spikes of holoTC, (2) delayed change of the total plasma B12 buffered by an internal Cbl depot, and (3) variations in the production/excretion velocities of MMA and Hcy. Bivariate distribution of the marker combinations (x, y) reveals several peaks of frequency in the analyzed mixed population. The peaks seem to represent the reference subgroups with different B12 physiology and characteristic values of “wellness parameter”: w = log10(holoTCn) + log10(B12n) − log10(MMAn) − log10(Hcyn), where concentrations are normalized (eg, MMAn = MMA/MMAnormal). Dynamic response of the organism to B12 intake is quantified and described as an additional analytical tool when classifying uncertain cases. The discussed mathematical approaches are of general applicability in diagnostics.Metabolic signs of vitamin B12 deficiency in humans: computational model and its implications for diagnosticsSergey N. Fedosov10.1016/j.metabol.2009.09.036Metabolism - Clinical and Experimental 59, 8 (2010)2010-01-06Metabolism - Clinical and Experimental2010-01-06598S0026-0495(10)X0007-511241138http://www.metabolismjournal.com/article/PIIS0026049509004806/abstract?rss=yesAbstract: We investigated the effects of the common polymorphisms in the peroxisome proliferator-activated receptor–γ (PPAR-γ; Pro12Ala) and in PPAR-γ coactivator–1(PGC-1; Gly482Ser) genes on the response to pioglitazone in Chinese with type 2 diabetes mellitus. A total of 250 patients with type 2 diabetes mellitus were treated with pioglitazone (30 mg/d) for 24 weeks without a change in previous medications. All patients were genotyped for the PPAR-γ Pro12Ala and PGC-1 Gly482Ser polymorphisms. The Ala12Ala and Pro12Ala genotypes (26.0% vs 13.5%, P = .025) and Ala allele (15.6% vs 7.3%, P = .008) were significantly more frequent in pioglitazone responders than in nonresponders. The distribution of PGC-1 genotypes and alleles was not significantly different between responders and nonresponders. The decrease in fasting glucose (50.4 ± 52.2 vs 43.3 ± 51.7 mg/dL, P < .001) and hemoglobin A1c (0.57% ± 1.44% vs 0.35% ± 1.10%, P = .004) levels was significantly greater in subjects with the Ala12 carriers (Pro12Ala and Ala12Ala) than in those without the allele (Pro12Pro). Baseline fasting glucose and triglyceride levels were related to the response of pioglitazone. Only the PPAR-γ Pro12Ala polymorphism was found to be associated with the response of pioglitazone by multiple logistic regression analysis. The PPAR-γ Pro12Ala gene polymorphism is associated with the response to pioglitazone in Chinese patients with type 2 diabetes mellitus. These findings may be helpful for targeted treatment of diabetes by identifying patients who are likely to respond to pioglitazone.Common polymorphisms of the peroxisome proliferator-activated receptor–γ (Pro12Ala) and peroxisome proliferator-activated receptor–γ coactivator–1 (Gly482Ser) and the response to pioglitazone in Chinese patients with type 2 diabetes mellitusMing-Chia Hsieh, Kun-Der Lin, Kai-Jen Tien, Shih-Te Tu, Jeng-Yueh Hsiao, Shun-Jen Chang, Shiu-Ru Lin, Shih-Jang Shing, Hung-Chun Chen10.1016/j.metabol.2009.10.030Metabolism - Clinical and Experimental 59, 8 (2010)2010-01-04Metabolism - Clinical and Experimental2010-01-04598S0026-0495(10)X0007-511391144http://www.metabolismjournal.com/article/PIIS0026049509004818/abstract?rss=yesAbstract: This study investigated the biochemical relationship between human follicular/oocyte maturity and the levels of follicular fluid purines. Intrafollicular levels of purine metabolites and creatinine are associated with oocyte presence, and the presence of such high levels of adenosine indicates a privileged site with no adenosine deaminase activity. Subgrouping according to oocyte recovery and fertilization revealed differences in correlation between the purine metabolites: Only where an oocyte was recovered and subsequently fertilized did follicular fluid adenosine, adenine, and hypoxanthine levels correlate with each other. Significantly, purines' correlation with levels of the terminal degradation product, uric acid, could only be seen in failed fertilization samples. Given the established metabolic pathways for adenosine triphosphate/adenosine diphosphate/adenosine monophosphate degradation, the results indicate maximization of 2 purine salvage pathways (from adenine and hypoxanthine) that pivot on the presence of high adenosine levels. Such optimized recovery may be necessary to build a store of salvaged adenosine phosphate for oocyte survival.High follicular fluid adenosine levels may be pivotal in the metabolism and recycling of adenosine nucleotides in the human follicleXuesong Wen, David Perrett, Nicola Jones, Amanda J. Tozer, Suzanne M. Docherty, Ray K. Iles10.1016/j.metabol.2009.09.037Metabolism - Clinical and Experimental 59, 8 (2010)2010-01-04Metabolism - Clinical and Experimental2010-01-04598S0026-0495(10)X0007-511451155http://www.metabolismjournal.com/article/PIIS002604950900482X/abstract?rss=yesAbstract: Receptors of the 5-HT2C subtype are of importance for the influence of serotonin on food intake, and 2 single nucleotide polymorphisms in this gene (HTR2C)—Cys23Ser (rs6318) and −759C>T (rs3813929)—have been reported to be associated with weight and/or antipsychotic-induced weight gain. The present study aimed to replicate these associations; in addition, the 5-HTTLPR polymorphism in the promoter region of the serotonin transporter gene (SLC6A4) was assessed. The polymorphisms were genotyped in subjects recruited from the normal population (n = 510), and possible associations between genotype and body mass index (BMI) were assessed. The Ser23 allele was more common in underweight subjects (BMI <20) than in normal- and overweight (BMI ≥20) subjects (P = .006). The T allele of the −759C/T polymorphism was less common in the overweight group (BMI ≥25) (P = .007). Homozygosity for the short allele of 5-HTTLPR was more frequent in underweight subjects (P = .015). Our results are in agreement with previous studies, suggesting polymorphisms in HTR2C to be associated with body weight, particularly in women; and they also suggest that 5-HTTLPR may influence this phenotype. Further studies on the importance of the investigated genes for eating disorders and drug-induced weight gain are warranted.Further exploration of the possible influence of polymorphisms in HTR2C and 5HTT on body weightJessica Bah, Lars Westberg, Fariba Baghaei, Susanne Henningsson, Roland Rosmond, Jonas Melke, Göran Holm, Elias Eriksson10.1016/j.metabol.2009.11.007Metabolism - Clinical and Experimental 59, 8 (2010)2010-01-21Metabolism - Clinical and Experimental2010-01-21598S0026-0495(10)X0007-511561163http://www.metabolismjournal.com/article/PIIS0026049509004843/abstract?rss=yesAbstract: Few studies have explored the relationship between individual and combined multiple indicators of socioeconomic status across the life course and the metabolic syndrome, or attempted to understand the mechanisms underlying any associations. The present study examined the associations between 4 indicators of socioeconomic status, individually and in combination, and metabolic syndrome risk in a study of male US veterans and examined the influence of health behaviors, intelligence, and psychologic distress on these associations. Participants (N = 4253) were drawn from the Vietnam Experience Study. From military service files, telephone interviews, and a medical examination, occupational, sociodemographic, health behavior, intelligence, psychologic, and health data were collected. The 4 indices of socioeconomic status were as follows: education achieved, early adulthood income, household income in midlife, and occupational prestige in midlife. Metabolic syndrome was diagnosed from the following: body mass index, fasting blood glucose or a diagnosis of diabetes, blood pressure—a diagnosis of hypertension or taking antihypertensives, high-density lipoprotein cholesterol, and triglyceride levels. In models that adjusted for age, men in the lower 2 groups on the combined measure of socioeconomic status experienced a higher risk of metabolic syndrome. This association was accounted for mainly by education achieved, household income in midlife, and occupational prestige in midlife. Intelligence appeared to explain much of this association. Combined socioeconomic status measures across the life course were related to metabolic syndrome but in a threshold rather than dose-response manner. Intelligence appeared to mediate this relationship.The influence of multiple indices of socioeconomic disadvantage across the adult life course on the metabolic syndrome: the Vietnam Experience StudyAnna C. Phillips, Douglas Carroll, G. Neil Thomas, Catharine R. Gale, Ian Deary, G. David Batty10.1016/j.metabol.2009.11.009Metabolism - Clinical and Experimental 59, 8 (2010)2010-01-04Metabolism - Clinical and Experimental2010-01-04598S0026-0495(10)X0007-511641171http://www.metabolismjournal.com/article/PIIS0026049509004855/abstract?rss=yesAbstract: Myocardial infarction affects a large population in the world. Lipid peroxide metabolism plays an important role in the pathology of myocardial infarction. This study aims to evaluate the preventive effect of caffeic acid on lipid peroxides, antioxidants, cardiac marker enzymes, and histopathological findings in isoproterenol (ISO)-induced myocardial-infarcted male Wistar rats. Myocardial infarction was induced in rats by subcutaneous injection of ISO (100 mg/kg) at an interval of 24 hours for 2 days. The ISO-induced rats showed significant increase in the levels of thiobarbituric acid reactive substances, lipid hydroperoxides in the heart, plasma uric acid, and serum cardiac marker enzymes, and significant decrease in the activities of heart superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, and the levels of reduced glutathione, vitamin E, and vitamin C in the plasma and heart. Oral pretreatment with caffeic acid (15 mg/kg) daily for 10 days showed significant decrease in the levels of serum cardiac marker enzymes, heart lipid peroxidation products and plasma uric acid and significant increase in the levels of antioxidant system. Histopathology of myocardium also confirmed the protective effect of caffeic acid in myocardial-infarcted rats. In vitro study on total antioxidant activity (2,2'-azinobis-[3-ethylbenzothiazoline-6-sulfonic acid]+ assay) confirmed the strong antioxidant action of caffeic acid. Thus, the present study revealed that caffeic acid ameliorates cardiac damage in ISO-induced myocardial infarction by maintaining lipid peroxide metabolism due to its free radical scavenging and antioxidant effects. A diet containing caffeic acid may be beneficial to myocardial infarction.Protective effect of caffeic acid on cardiac markers and lipid peroxide metabolism in cardiotoxic rats: an in vivo and in vitro studyK. Senthil Kumaran, P. Stanely Mainzen Prince10.1016/j.metabol.2009.11.010Metabolism - Clinical and Experimental 59, 8 (2010)2010-01-04Metabolism - Clinical and Experimental2010-01-04598S0026-0495(10)X0007-511721180http://www.metabolismjournal.com/article/PIIS0026049509004867/abstract?rss=yesAbstract: The objective of the study was to evaluate the accuracy of established prediction equations that calculate resting energy expenditure (REE) in obese women. This was a cross-sectional study. In 273 mildly to severely obese women (age, 41.7 ± 13.2 years; body mass index, 42.8 ± 7.0 kg/m2), REE was measured by indirect calorimetry (mREE), along with fat mass (FM) and fat-free mass (FFM) by bioelectrical impedance analysis. Eleven established equations were used to predict REE (pREE), with 9 equations basing on the anthropometric parameters body weight and height and 2 equations including body composition parameters (FM, FFM). All equations provided pREE values that significantly correlated with mREE (r > 0.66, P < .001), although 8 equations systematically underestimated mREE (P < .05). Of note, even the best equation was not able to accurately predict mREE with a deviation of less than ±10% in more than 70% of the tested women. Furthermore, equations using body composition data were not superior in predicting REE as compared with equations exclusively including anthropometric variables. Multiple linear regression analyses revealed 2 new equations—one including body weight and age and another including FM, FFM, and age—that explained 56.9% and 57.2%, respectively, of variance in mREE. However, when these 2 new equations were applied to an independent sample of 33 obese women, they also provided an accurate prediction (±10%) of mREE in only 56.7% and 60.6%, respectively, of the women. Data show that an accurate prediction of REE is not feasible using established equations in obese women. Equations that include body composition parameters as assessed by bioelectrical impedance analysis do not increase the accuracy of prediction. Based on our results, we conclude that calculating REE by standard prediction equations does not represent a reliable alternative to indirect calorimetry for the assessment of REE in obese women.Poor prediction of resting energy expenditure in obese women by established equationsBritta Wilms, Sebastian M. Schmid, Barbara Ernst, Martin Thurnheer, Manfred J. Mueller, Bernd Schultes10.1016/j.metabol.2009.11.011Metabolism - Clinical and Experimental 59, 8 (2010)2010-01-04Metabolism - Clinical and Experimental2010-01-04598S0026-0495(10)X0007-511811189http://www.metabolismjournal.com/article/PIIS0026049509004879/abstract?rss=yesAbstract: The purpose of this study was to examine the effects of Carnipure tartrate (Lonza, Allendale, NJ) supplementation (total dose of 2 g/d of l-carnitine) on markers of performance and recovery from physical exertion in middle-aged men and women. Normally active and healthy men (n = 9, 45.4 ± 5.3 years old) and women (n = 9, 51.9 ± 5.0 years old) volunteered to participate in the investigation. Double-blind, placebo, balanced treatment presentation and crossover design were used with 3 weeks and 3 days of supplementation followed by a 1-week washout period before the other counterbalanced treatment was initiated. After 3 weeks of each supplementation protocol, each participant then performed an acute resistance exercise challenge of 4 sets of 15 repetitions of squat/leg press at 50% 1-repetition maximum and continued supplementation over the recovery period that was evaluated. Blood samples were obtained at preexercise and at 0, 15, 30, and 120 minutes postexercise during the acute resistance exercise challenge and during 4 recovery days as well. Two grams of l-carnitine supplementation had positive effects and significantly (P ≤ .05) attenuated biochemical markers of purine metabolism (ie, hypoxanthine, xanthine oxidase), free radical formation (malondialdehyde), muscle tissue disruption (myoglobin, creatine kinase), and muscle soreness after physical exertion. However, markers of physical performance (ie, strength, power, get up and go) were not affected by supplementation. These findings support our previous findings of l-carnitine in younger people that such supplementation can reduce chemical damage to tissues after exercise and optimize the processes of muscle tissue repair and remodeling.l-Carnitine l-tartrate supplementation favorably affects biochemical markers of recovery from physical exertion in middle-aged men and womenJen-Yu Ho, William J. Kraemer, Jeff S. Volek, Maren S. Fragala, Gwendolyn A. Thomas, Courtenay Dunn-Lewis, Michael Coday, Keijo Häkkinen, Carl M. Maresh10.1016/j.metabol.2009.11.012Metabolism - Clinical and Experimental 59, 8 (2010)2010-01-04Metabolism - Clinical and Experimental2010-01-04598S0026-0495(10)X0007-511901199http://www.metabolismjournal.com/article/PIIS0026049509004880/abstract?rss=yesAbstract: The importance of hypertension treatment has expanded beyond blood pressure management to include additional risk factors, mainly diabetes. It was considered of interest to test the effect of telmisartan, an angiotensin receptor 1 antagonist and peroxisome proliferator activator receptor–γ partial agonist, on Cohen-Rosenthal diabetic hypertensive nonobese (CRDH) rats, a unique model combining both pathologies. Its effect was examined on fat-derived and inflammatory agents in CRDH. To determine the extent of the drug's peroxisome proliferator activator receptor–γ modulating beneficial metabolic actions, results were compared with those obtained with valsartan and rosiglitazone in CRDH and Cohen diabetic rat (CDR). Telmisartan and valsartan were given in drinking water at 3 and 12 mg/kg/d, whereas rosiglitazone (3 mg/kg/d) was given as food admixture for a period of 5 months. Blood pressure, glucose, insulin, adiponectin, leptin, and tumor necrosis factor α were examined. Telmisartan and valsartan significantly (P < .01) reduced blood pressure, whereas telmisartan and rosiglitazone considerably reduced blood glucose levels to normoglycemic levels (P < .01) in these 2 strains. Insulin levels were not affected by telmisartan and valsartan but were slightly reduced by rosiglitazone in CDR. In contrast to valsartan, adiponectin was significantly (60%, P < .01) increased by telmisartan in both CDR and CRDH, whereas rosiglitazone induced a 60% and 180% increase in CRDH and CDR animals, respectively, on day 30 of treatment. Co-treatment with GW9662 averted telmisartan-induced rise of adiponectin. Tumor necrosis factor α declined in telmisartan-treated rats, less so with rosiglitazone, but not valsartan. Telmisartan also induced downsizing of epididymal adipocytes compared with valsartan. Leptin levels were significantly increased by valsartan (P < .05) but reduced by telmisartan and rosiglitazone. The telmisartan-induced increase in adiponectin was most probably associated with a decrease in glucose and tumor necrosis factor α levels. Therefore, in addition to its hypotensive effect, telmisartan demonstrated beneficial thiazolidinedione-like effects.Telmisartan ameliorates hyperglycemia and metabolic profile in nonobese Cohen-Rosenthal diabetic hypertensive rats via peroxisome proliferator activator receptor–γ activationFiras Younis, Naftali Stern, Rona Limor, Yoram Oron, Sarah Zangen, Talma Rosenthal10.1016/j.metabol.2009.11.013Metabolism - Clinical and Experimental 59, 8 (2010)2010-01-14Metabolism - Clinical and Experimental2010-01-14598S0026-0495(10)X0007-512001209http://www.metabolismjournal.com/article/PIIS0026049509004892/abstract?rss=yesAbstract: It is becoming more evident that age, gender, and race play a significant role in the metabolic profiles that are seen among individuals in a clinical setting. It is important to understand these variances in metabolic profiles; and with these variances in mind it is now possible to understand why a single diet might not decrease cardiovascular disease risk profiles uniformly for everyone. Much is now understood about triglyceride metabolism and its contribution to energy storage. In this review we will focus on triglycerides; their production, metabolism and influence on daily life, as well as the various methods for the treatment of hypertryglyceridemia and prevention of its sequelae.Current concepts in triglyceride metabolism, pathophysiology, and treatmentGeorges AbouRjaili, Norbert Shtaynberg, Robert Wetz, Thomas Costantino, George S. Abela10.1016/j.metabol.2009.11.014Metabolism - Clinical and Experimental 59, 8 (2010)2010-01-08Metabolism - Clinical and Experimental2010-01-08598S0026-0495(10)X0007-512101220http://www.metabolismjournal.com/article/PIIS0026049509004909/abstract?rss=yesAbstract: The objective of the study was to investigate whether changes in liver mitochondrial energetics could underlie the enhanced energetic efficiency that drives accelerated body fat recovery (catch-up fat) during refeeding after caloric restriction. Rats were subjected to caloric restriction (50% of ad libitum intake) for 15 days and then refed for 1 or 2 weeks on an amount of chow equal to that of controls matched for weight at the onset of refeeding. Whole-body metabolism was characterized by energy balance and body composition determinations as well as by indirect calorimetric measurements of 24-hour energy expenditure, substrate oxidation, and whole-body de novo lipogenesis estimated from nonprotein respiratory quotient. Hepatic mitochondrial energetics were determined from measurements of liver mitochondrial mass, respiratory capacities, and proton leak (both basal and fatty acid stimulated), whereas hepatic oxidative status was assessed from measurements of hepatic mitochondrial lipid peroxidation, aconitase, and superoxide dismutase activity. Furthermore, hepatic lipogenic capacity was determined from assays of fatty acid synthase activity. Compared with controls, isocalorically refed rats showed an elevated energetic efficiency and body fat gain over both week 1 and week 2 of refeeding, as well as a lower 24-hour energy expenditure and higher rates of whole-body de novo lipogenesis at the end of both week 1 and week 2 of refeeding. Analysis of the liver revealed that after 1 week (but not after 2 weeks) of refeeding, the mitochondrial mass (but not mitochondrial density) was lower in refed rats than in controls, associated with higher state 3 mitochondrial respiratory capacity, increased superoxide dismutase activity, as well as higher fatty acid synthase activity. These results suggest that, although at the whole-body level elevations in energy efficiency and de novo lipogenesis are coordinated toward catch-up fat, the overall hepatic mitochondrial energetic status during refeeding is more consistent with a contributory role of the liver in the enhanced de novo lipogenic machinery during catch-up fat rather than in the energy-conservation mechanisms (elevated energetic efficiency) that spare energy for catch-up fat.Hepatic mitochondrial energetics during catch-up fat after caloric restrictionRaffaella Crescenzo, Francesca Bianco, Italia Falcone, Marina Prisco, Abdul G. Dulloo, Giovanna Liverini, Susanna Iossa10.1016/j.metabol.2009.11.015Metabolism - Clinical and Experimental 59, 8 (2010)2010-01-04Metabolism - Clinical and Experimental2010-01-04598S0026-0495(10)X0007-512211230http://www.metabolismjournal.com/article/PIIS0026049509005022/abstract?rss=yesAbstract: We tested the hypothesis that risk of early mortality from cancers of the digestive system will be greater in men with, compared with men without, the metabolic syndrome (MetS). Participants were 33 230 men who were seen at the Cooper Clinic in Dallas, TX, and followed for 14.4 (SD = 7.0) years. Metabolic syndrome was defined as having at least 3 of the following risk factors: abdominal obesity, fasting hypertriglyceridemia, low high-density lipoprotein cholesterol, high blood pressure, or high fasting glucose level or diabetes. Metabolic syndrome was associated with higher mortality (hazard ratio [HR] = 1.90 [95% confidence interval = 1.42-2.55]), and there was a graded positive association for the addition of more syndrome components (P < .01). Adjustment for cardiorespiratory fitness attenuated the risk estimates by 20% to 30%, but they remained significant after this adjustment. Evaluation of the independent contribution of each of the syndrome components revealed that both abdominal obesity (HR = 1.89 [1.36-2.62]) and high glucose (HR = 1.38 [1.02-1.87]) were independently associated with cancer mortality. Our results support the hypothesis that metabolic syndrome is positively associated with mortality from cancers of the digestive system. Interventions that reduce abnormalities associated with the syndrome could reduce risk of premature death from these cancers.Metabolic syndrome and risk of death from cancers of the digestive systemCharles E. Matthews, Xuemei Sui, Michael J. LaMonte, Swann A. Adams, James R. Hébert, Steven N. Blair10.1016/j.metabol.2009.11.019Metabolism - Clinical and Experimental 59, 8 (2010)2010-01-04Metabolism - Clinical and Experimental2010-01-04598S0026-0495(10)X0007-512311239http://www.metabolismjournal.com/article/PIIS0026049510001915/abstract?rss=yesTable of Contents10.1016/S0026-0495(10)00191-5Metabolism - Clinical and Experimental 59, 8 (2010)2010-08-01Metabolism - Clinical and Experimental2010-08-01598S0026-0495(10)X0007-5FrontmatterA1A2http://www.metabolismjournal.com/article/PIIS0026049510001927/abstract?rss=yesEditorial Board10.1016/S0026-0495(10)00192-7Metabolism - Clinical and Experimental 59, 8 (2010)2010-08-01Metabolism - Clinical and Experimental2010-08-01598S0026-0495(10)X0007-5FrontmatterA3A3http://www.metabolismjournal.com/article/PIIS0026049510001939/abstract?rss=yesNotes to Contributors10.1016/S0026-0495(10)00193-9Metabolism - Clinical and Experimental 59, 8 (2010)2010-08-01Metabolism - Clinical and Experimental2010-08-01598S0026-0495(10)X0007-5FrontmatterA4A4