Reduced metabolic rate may contribute to weight gain in leptin-deficient ( ob/ob) mice; however, available studies have been criticized for referencing O 2 consumption (V˙o 2 ) to estimated rather than true lean body mass. To evaluate whether leptin deficiency reduces energy expenditure, four separate experiments were performed: 1) NMR spectroscopy was used to measure fat and nonfat mass, permittingV˙o 2 to be referenced to true nonfat mass; 2) dietary manipulation was used in an attempt to eliminate differences in body weight and composition between ob/ob and C57BL/6J mice; 3) short-term effects of exogenous leptin (0.3 mg ⋅ kg −1 ⋅ day −1 ) on V˙o 2 were examined; and 4) body weight and composition were compared in leptin-repleted and pair-fed ob/ob animals. ob/ob animals had greater mass, less lean body mass, and a 10% higher metabolic rate whenV˙o 2 was referenced to lean mass. Dietary manipulation achieved identical body weight in ob/ob and C57BL/6J animals; however, despite weight gain in C57BL/6J animals, percent fat mass remained higher in ob/ob animals (55 vs. 30%). Exogenous leptin increasedV˙o 2 in ob/ob but not control animals. Weight loss in leptin-repleted ob/ob mice was greater than in pair-fed animals (45 vs. 17%). We conclude, on the basis of the observed increase inV˙o 2 and accelerated weight loss seen with leptin repletion, that leptin deficiency causes a reduction in metabolic rate in ob/obmice. In contrast, these physiological studies suggest that comparison of V˙o 2 in obese and lean animals does not produce useful information on the contribution of leptin to metabolism.
Image-guided, spatially localized 31 P magnetic resonance spectroscopy (MRS) was used to study in vivo murine cardiac metabolism under resting and dobutamine-induced stress conditions. Intravenous dobutamine infusion (24 μg · min –1 · kg body wt –1 ) increased the mean heart rate by ∼39% from 482 ± 46 per min at baseline to 669 ± 77 per min in adult mice. The myocardial phosphocreatine (PCr)-to-ATP (PCr/ATP) ratio remained unchanged at 2.1 ± 0.5 during dobutamine stress, compared with baseline conditions. Therefore, we conclude that a significant increase in heart rate does not result in a decline in the in vivo murine cardiac PCr/ATP ratio. These observations in very small mammals, viz., mice, at extremely high heart rates are consistent with studies in large animals demonstrating that global levels of high-energy phosphate metabolites do not regulate in vivo myocardial metabolism during physiologically relevant increases in cardiac work.
FRASER, CHARLES D. JR.; CHACKO, V. P.; JACOBUS, WILLIAM E.; HUTCHINS, GROVER M.; GLICKSON, JERRY; REITZ, BRUCE A.; BAUMGARTNER, WILLIAM A. Author Information
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCarbon-13 CP-MAS NMR spectra of paramagnetic solidsV. P. Chacko, S. Ganapathy, and R. G. BryantCite this: J. Am. Chem. Soc. 1983, 105, 16, 5491–5492Publication Date (Print):August 1, 1983Publication History Published online1 May 2002Published inissue 1 August 1983https://pubs.acs.org/doi/10.1021/ja00354a058https://doi.org/10.1021/ja00354a058research-articleACS PublicationsRequest reuse permissionsArticle Views187Altmetric-Citations35LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
ATP and creatine phosphate (PCr) are prime myocardial high-energy phosphates. Their relative concentrations are conserved among mammalian species and across a range of physiologic cardiac workloads. The cardiac PCr/ATP ratio is decreased with several pathologic conditions, such as ischemia and heart failure, but there are no reports of an increase in the cardiac PCr/ATP ratio in any species or with interventions. We studied the in vivo energetics in transgenic mice lacking expression of the glucose transport protein GLUT4 (G4N) and observed a significant 60% increase in the myocardial PCr/ATP ratio in G4N that was confirmed in three different experimental settings including intact animals. The higher PCr/ATP in G4N is cardiac-specific and is due to higher total cardiac creatine (CR) concentrations in G4N than in wild-type (WT). However, [ATP], [ADP], and -DG(-ATP) did not differ between the strains. Expression of the creatine transport protein (CreaT) that is responsible for creatine uptake in myocytes was preserved in G4N cardiac tissue. These observations demonstrate, for the first time to our knowledge, that G4N manifest a unique increase in the cardiac PCr/ATP ratio, which suggests a novel genetic strategy for increasing myocardial creatine levels.
Objective: The effect of coronary perfusion on left ventricular chamber distensibility is only indirect evidence that perfusion alters the mechanical properties of the myocardium. The aim of this study was to demonstrate explicitly the effects of coronary perfusion on these mechanical properties. Methods: The effects of different levels of coronary perfusion were studied both on in-plane stress-strain relations and on transverse stiffness in an isolated, perfused canine interventricular septal preparation. Additionally, to determine the vascular compartment responsible for the mechanical effects of perfusion on tissue properties, we examined the in-plane stress-strain responses and transverse stiffness after embolisation of the vasculature with 15 μm microspheres. Results: The data show a clear dependence of tissue stress-strain properties on perfusion. The in-plane stress-strain relations were shifted to the left and transverse stiffness increased linearly as septal artery perfusion pressure increased. The dependence of both the in-plane stress-strain relations and transverse stiffness on perfusion was significantly decreased following embolisation. Conclusions: Myocardial tissue stiffness is directly related to perfusion. The linear relationship between transverse stiffness and perfusion makes it easier to assess the effects of perfusion on tissue stiffness than with in-plane stress-strain relations. Perfusion of capillaries and/or venules is largely responsible for these alterations in myocardial stiffness. Cardiovascular Research 1993;27:403-410
Prior transient episodes of ischemia ("ischemic preconditioning") reduce lactate accumulation and attenuate acidosis during a subsequent prolonged ischemic insult. The mechanisms responsible for attenuated glycolytic catabolite accumulation have not been established but may include earlier exhaustion of glycogen stores, slowed glycogenolysis before complete glycogen depletion, and/or inhibition of glycolysis. Simultaneous repeated measures of myocardial glycogen and the rates of glycolysis, glycogenolysis, glucose utilization, and glycolytic ATP production were obtained during total ischemia by 13C nuclear magnetic resonance spectroscopy in control and ischemia-preconditioned isolated rat hearts. Both [13C]glycolytic and [13C]glycogenolytic rates were significantly lower during total ischemia in preconditioned compared with control hearts (0.77 +/- 0.04 versus 1.06 +/- 0.06 mumol/min per gram wet weight [P < .01] for glycolysis and 0.15 +/- 0.07 versus 0.78 +/- 0.12 mumol/ min per gram wet weight [P < .001] for glycogenolysis, respectively, at 2.5 minutes of ischemia). Slowed glycolysis was present even during the early minutes of ischemia, when significant amounts of available [13C]glycogen were still present. Importantly, the reduction in the rate of glycogenolysis was larger and out of proportion to the reduction in glycolysis and occurred despite an increase in glucose utilization in preconditioned hearts (2.23 +/- 0.15 versus 1.5 +/- 0.10 mumol/min per gram wet weight at 1.25 minutes, P < .01). During early ischemia, conversion of glycogen phosphorylase to the a or "active" form was less in preconditioned than in control hearts (29.1 +/- 2.6% versus 41.2 +/- 9.8%, respectively; P < .05). Taken together, these findings demonstrate that ischemic preconditioning significantly depresses glycolytic catabolite accumulation during sustained ischemia not by more severe glycolytic inhibition or exhaustion of glycogen stores but by depressed glycogenolysis from the onset of ischemia.
The development of a noninvasive screening test for the detection of cardiac allograft rejection would improve the potential for management of heart transplant recipients. To assess the possibility that changes in myocardial high-energy phosphate metabolism precede frank rejection, 17 beagles received cervical cardiac allografts. Recipients underwent serial phosphorus 31 nuclear magnetic resonance spectroscopy, endocardial biopsy (blindly graded, 0 to 8), and left ventricular pressure measurements starting on the day of surgery. The first (less than 24 hours) spectrum was considered the baseline for all additional studies. The phosphocreatine to inorganic phosphate ratio (PCr/Pi), an index of myocardial bioenergetic supply/demand balance, was determined and expressed as a percentage of baseline of initial and all subsequent spectra. To evaluate the predictive utility of the PCr/Pi ratio, a 50% decrease from baseline was designated as a positive test and was correlated with biopsy-proved rejection (score greater than 3). When PCr/Pi values were compared with the subsequent day's biopsy score, we observed a 91% sensitivity, 90% specificity, and a predictive value of 92%. We conclude that the PCr/Pi ratio is sensitive in predicting heterotopic allograft rejection in its earliest stages. Thus phosphorus 31 nuclear magnetic resonance holds promise for clinical use in the noninvasive diagnosis and monitoring of cardiac rejection.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCarbon-13 CP/MAS NMR and crystallographic investigations of the structure and solid-state transformations of lead(II) acetate trihydrateRobert G. Bryant, V. P. Chacko, and Margaret C. EtterCite this: Inorg. Chem. 1984, 23, 22, 3580–3584Publication Date (Print):October 1, 1984Publication History Published online1 May 2002Published inissue 1 October 1984https://pubs.acs.org/doi/10.1021/ic00190a029https://doi.org/10.1021/ic00190a029research-articleACS PublicationsRequest reuse permissionsArticle Views297Altmetric-Citations54LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
