phosphocreatine and Obesity

There is convincing evidence that alterations in myocardial substrate use play an important role in the normal and diseased heart. In this review, insights gained by using quantitative molecular imaging by positron emission tomography and magnetic resonance spectroscopy in the study of human myocardial metabolism will be discussed, and attention will be paid to the effects of nutrition, gender, aging, obesity, diabetes, cardiac hypertrophy, ischemia, and heart failure. The heart is an omnivore organ, relying on metabolic flexibility, which is compromised by the occurrence of defects in coronary flow reserve, insulin-mediated glucose disposal, and metabolic-mechanical coupling. Obesity, diabetes, and ischemic cardiomyopathy appear as states of high uptake and oxidation of fatty acids, that compromise the ability to utilize glucose under stimulated conditions, and lead to misuse of energy and oxygen, disturbing mechanical efficiency. Idiopathic heart failure is a complex disease frequently coexisting with diabetes, insulin resistance and hypertension, in which the end stage of metabolic toxicity manifests as severe mitochondrial disturbance, inability to utilize fatty acids, and ATP depletion. The current literature provides evidence that the primary events in the metabolic cascade outlined may originate in extra-cardiac organs, since fatty acid, glucose levels, and insulin action are mostly controlled by adipose tissue, skeletal muscle and liver, and that a broader vision of organ cross-talk may further our understanding of the primary and the adaptive events involved in metabolic heart toxicity.

Topics: Adenosine Triphosphate; Aging; Diabetes Mellitus; Energy Metabolism; Fatty Acids; Female; Glucose; Heart Diseases; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Myocardial Ischemia; Myocardium; Obesity; Oxygen Consumption; Phosphocreatine; Positron-Emission Tomography; Sex Factors

Topics: Adenosine Triphosphate; Anatomy, Comparative; Animals; Blood Glucose; Brain Stem; Cachexia; Cats; Cerebral Ventricles; Electric Stimulation; Enteral Nutrition; Feedback; Feeding and Eating Disorders; Feeding Behavior; Globus Pallidus; Goats; Haplorhini; Humans; Hunger; Hypothalamus; Limbic System; Liver; Motor Cortex; Norepinephrine; Obesity; Phosphocreatine; Physiology, Comparative; Rabbits; Rats; Self Stimulation; Sheep; Starvation

Few studies have assessed the relationship between GH and mitochondrial function.. The objective of this study was to determine the effects of improving IGF-I using a GHRH analog, tesamorelin, on mitochondrial function assessed by phosphocreatine (PCr) recovery using (31)P magnetic resonance spectroscopy in obese adults with reduced GH.. A total of 39 obese men and women with reduced GH secretion as determined by GHRH-arginine stimulation tests underwent magnetic resonance spectroscopy as part of a 12-month, double-blind, randomized, placebo-controlled trial comparing tesamorelin vs placebo. PCr recovery after submaximal exercise was assessed at baseline and at 12 months.. At baseline, there were no differences in age, sex, race/ethnicity, and GH or PCr parameters between tesamorelin and placebo. After 12 months, tesamorelin treatment led to a significantly greater increase in IGF-I than did placebo treatment (change, 102.9±31.8 μg/L vs 22.8±8.9 μg/L, tesamorelin vs placebo; P=.02). We demonstrated a significant positive relationship between increases in IGF-I and improvements in PCr recovery represented as ViPCr (R=0.56; P=.01). The association between IGF-I and PCr recovery was even stronger among subjects treated with tesamorelin only (ViPCr: R=0.71; P=.03). This association remained significant after controlling for age, sex, race, ethnicity, and parameters of body composition and insulin sensitivity (all P<.05).. Increases in IGF-I from 12 months of treatment with tesamorelin were significantly associated with improvements in PCr recovery parameters in obese men and women with reduced GH secretion, suggestive of improvements in mitochondrial function.

Topics: Adult; Double-Blind Method; Exercise; Female; Growth Hormone-Releasing Hormone; Human Growth Hormone; Humans; Hypopituitarism; Insulin-Like Growth Factor I; Male; Middle Aged; Obesity; Phosphocreatine; Placebos; Young Adult

Very limited data suggest that meat consumption by older people may promote skeletal muscle hypertrophy in response to resistance training (RT).. The objective of this study was to assess whether the consumption of an omnivorous (meat-containing) diet would influence RT-induced changes in whole-body composition and skeletal muscle size in older men compared with a lactoovovegetarian (LOV) (meat-free) diet.. Nineteen men aged 51-69 y participated in the study. During a 12-wk period of RT, 9 men consumed their habitual omnivorous diets, which provided approximately 50% of total dietary protein from meat sources (beef, poultry, pork, and fish) (mixed-diet group). Another 10 men were counseled to self-select an LOV diet (LOV-diet group).. Maximal strength of the upper- and lower-body muscle groups that were exercised during RT increased by 10-38% (P < 0.001), independent of diet. The RT-induced changes in whole-body composition and skeletal muscle size differed significantly between the mixed- and LOV-diet groups (time-by-group interactions, P < 0. 05). With RT, whole-body density, fat-free mass, and whole-body muscle mass increased in the mixed diet group but decreased in the LOV- diet group. Type II muscle fiber area of the vastus lateralis muscle increased with RT for all men combined (P < 0.01), and the increase tended to be greater in the mixed-diet group (16.2 +/- 4.4 %) than in the LOV diet group (7.3 +/- 5.1%). Type I fiber area was unchanged with RT in both diet groups.. Consumption of a meat-containing diet contributed to greater gains in fat-free mass and skeletal muscle mass with RT in older men than did an LOV diet.

Topics: Aged; Body Composition; Creatine; Diet; Diet, Vegetarian; Exercise; Humans; Male; Meat; Middle Aged; Muscle, Skeletal; Obesity; Phosphocreatine

The mechanisms promoting disturbed white adipocyte function in obesity remain largely unclear. Herein, we integrate white adipose tissue (WAT) metabolomic and transcriptomic data from clinical cohorts and find that the WAT phosphocreatine/creatine ratio is increased and creatine kinase-B expression and activity is decreased in the obese state. In human in vitro and murine in vivo models, we demonstrate that decreased phosphocreatine metabolism in white adipocytes alters adenosine monophosphate-activated protein kinase activity via effects on adenosine triphosphate/adenosine diphosphate levels, independently of WAT beigeing. This disturbance promotes a pro-inflammatory profile characterized, in part, by increased chemokine (C-C motif) ligand 2 (CCL2) production. These data suggest that the phosphocreatine/creatine system links cellular energy shuttling with pro-inflammatory responses in human and murine white adipocytes. Our findings provide unexpected perspectives on the mechanisms driving WAT inflammation in obesity and may present avenues to target adipocyte dysfunction.

Topics: Adipocytes, White; Animals; Creatine; Humans; Inflammation; Mice; Obesity; Phosphocreatine

Adaptive thermogenesis has attracted much attention because of its ability to increase systemic energy expenditure and to counter obesity and diabetes

Topics: Adipocytes; Adipose Tissue, Brown; Alkaline Phosphatase; Animals; Cold Temperature; Energy Metabolism; Hydrolysis; Male; Mice; Mice, Inbred C57BL; Microscopy, Electron, Transmission; Mitochondria; Mitochondrial Proteins; Obesity; Phosphocreatine; Thermogenesis

We previously reported that higher body mass index (BMI) was associated with greater hippocampal glutamate+glutamine in people with bipolar disorder (BD), but not in non-BD healthy comparator subjects (HSs). In the current report, we extend these findings by examining the impact of BD diagnosis and BMI on hippocampal volumes and the concentrations of several additional neurochemicals in 57 early-stage BD patients and 31 HSs. Using 3-T magnetic resonance imaging and magnetic resonance spectroscopy, we measured bilateral hippocampal volumes and the hippocampal concentrations of four neurochemicals relevant to BD: N-acetylaspartate+N-acteylaspartylglutamate (tNAA), creatine+phosphocreatine (Cre), myoinositol (Ins) and glycerophosphocholine+phosphatidylcholine (Cho). We used multivariate factorial analysis of covariance to investigate the impact of diagnosis (patient vs HS) and BMI category (normal weight vs overweight/obese) on these variables. We found a main effect of diagnosis on hippocampal volumes, with patients having smaller hippocampi than HSs. There was no association between BMI and hippocampal volumes. We found diagnosis and BMI effects on hippocampal neurochemistry, with patients having lower Cre, Ins and Cho, and overweight/obese subjects having higher levels of these chemicals. In patient-only models that controlled for clinical and treatment variables, we detected an additional association between higher BMI and lower tNAA that was absent in HSs. To our knowledge, this was the first study to investigate the relative contributions of BD diagnosis and BMI to hippocampal volumes, and only the second to investigate their contributions to hippocampal chemistry. It provides further evidence that diagnosis and elevated BMI both impact limbic brain areas relevant to BD.

Topics: Adolescent; Adult; Aspartic Acid; Bipolar Disorder; Body Mass Index; Brain; Case-Control Studies; Creatine; Dipeptides; Female; Hippocampus; Humans; Image Processing, Computer-Assisted; Inositol; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Obesity; Organ Size; Overweight; Phosphatidylcholines; Phosphocreatine; Young Adult

Skeletal muscles require energy either at constant low (e.g., standing and posture) or immediate high rates (e.g., exercise). To fulfill these requirements, myocytes utilize the phosphocreatine (PCr)/creatine (Cr) system as a fast energy buffer and shuttle. We have generated mice lacking L-arginine:glycine amidino transferase (AGAT), the first enzyme of creatine biosynthesis. These AGAT(-/-) (d/d) mice are devoid of the PCr/Cr system and reveal severely altered oxidative phosphorylation. In addition, they exhibit complete resistance to diet-induced obesity, which is associated with a chronic activation of AMP-activated protein kinase in muscle and white adipose tissue. The underlying metabolic rearrangements have not yet been further analyzed. Here, we performed gene expression analysis in skeletal muscle and a serum amino acid profile of d/d mice revealing transcriptomic and metabolic alterations in pyruvate and glucose pathways. Differential pyruvate tolerance tests demonstrated preferential conversion of pyruvate to alanine, which was supported by increased protein levels of enzymes involved in pyruvate and alanine metabolism. Pyruvate tolerance tests suggested severely impaired hepatic gluconeogenesis despite increased availability of pyruvate and alanine. Furthermore, enzymes of serine production and one-carbon metabolism were significantly up-regulated in d/d mice, indicating increased de novo formation of one-carbon units from carbohydrate metabolism linked to NAD(P)H production. Besides the well-established function of the PCr/Cr system in energy metabolism, our transcriptomic and metabolic analyses suggest that it plays a pivotal role in systemic one-carbon metabolism, oxidation/reduction, and biosynthetic processes. Therefore, the PCr/Cr system is not only an energy buffer and shuttle, but also a crucial component involved in numerous systemic metabolic processes.

Topics: Adipose Tissue, White; Amidinotransferases; Amino Acid Metabolism, Inborn Errors; Animals; Developmental Disabilities; Intellectual Disability; Metabolome; Mice; Mice, Knockout; Muscle, Skeletal; Obesity; Oxidative Phosphorylation; Phosphocreatine; Speech Disorders; Transcriptome

Phosphorus magnetic resonance spectroscopy ((31)P-MRS) enables the non-invasive evaluation of muscle metabolism. Resting Pi-to-ATP flux can be assessed through magnetization transfer (MT) techniques, and maximal oxidative flux (Q(max)) can be calculated by monitoring of phosphocreatine (PCr) recovery after exercise. In this study, the muscle metabolism parameters of 13 overweight-to-obese sedentary individuals were measured with both MT and dynamic PCr recovery measurements, and the interrelation between these measurements was investigated. In the dynamic experiments, knee extensions were performed at a workload of 30% of maximal voluntary capacity, and the consecutive PCr recovery was measured in a quadriceps muscle with a time resolution of 2 s with non-localized (31)P-MRS at 3 T. Resting skeletal muscle metabolism was assessed through MT measurements of the same muscle group at 7 T. Significant linear correlations between the Q(max) and the MT parameters k(ATP) (r = 0.77, P = 0.002) and F(ATP) (r = 0.62, P = 0.023) were found in the study population. This would imply that the MT technique can possibly be used as an alternative method to assess muscle metabolism when necessary (e.g. in individuals after stroke or in uncooperative patients).

Topics: Adenosine Triphosphate; Adult; Exercise; Female; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Obesity; Oxidation-Reduction; Phosphocreatine; Phosphorus; Phosphorus Isotopes; Quadriceps Muscle; Rest; Sedentary Behavior; Time Factors; Young Adult

A reduced myocardial phosphocreatine/adenosine triphosphate (PCr/ATP) ratio is linked to both diastolic dysfunction and heart failure. Although obesity is well known to cause diastolic dysfunction a link to impaired cardiac energetics has only recently been established. We assessed whether or not long-term weight loss in obesity, which is known to reduce mortality, is accompanied by both improved cardiac energetics and diastolic function. Normal weight (BMI 22 ± 2; n = 18) and obese subjects (BMI 34 ± 4; n = 13) underwent cine-MRI (1.5 Tesla) to determine left ventricular diastolic function using volume-time curve analysis, and (31)P-MR spectroscopy (3 Tesla) to assess cardiac energetics (PCr/ATP ratio). Obese subjects (n = 13) underwent repeat assessment after 1 year of supervised weight loss. Obesity, in the absence of identifiable cardiovascular risk factors, was associated with significantly impaired myocardial high energy phosphate metabolism (PCr/ATP ratio, normal; 2.03 ± 0.27 vs. obese; 1.58 ± 0.47, p = 0.002) and significantly lower peak diastolic filling rate (normal; 4.8 ± 0.8 vs. obese; 3.8 ± 0.7 EDV/s, p = 0.01). Weight loss (on average 9 kg, 55% excess weight) over 1 year resulted in a 24% increase in PCr/ATP ratio (p = 0.01) and an 18% improvement in peak diastolic filling rate (p = 0.01). Myocardial PCr/ATP ratio remained positively correlated with peak diastolic filling rate after weight loss (r = 0.63, p = 0.02). In obesity, weight loss improves impaired cardiac energetics and myocardial relaxation. Improved myocardial energetics appear to play a key role in diastolic functional recovery accompanying weight loss.

Topics: Adenosine Triphosphate; Adiposity; Adult; Body Mass Index; Diastole; Energy Metabolism; Humans; Magnetic Resonance Imaging, Cine; Magnetic Resonance Spectroscopy; Middle Aged; Myocardium; Obesity; Phosphocreatine; Recovery of Function; Time Factors; Treatment Outcome; Ventricular Function, Left; Weight Loss

Obesity has become an epidemic in children, associated with an increase in insulin resistance and metabolic dysfunction. Mitochondrial function is known to be an important determinant of glucose metabolism in adults. However, little is known about the relationship between mitochondrial function and obesity, insulin resistance, energy expenditure, and pubertal development in children.. Seventy-four participants, 37 overweight (> or = 85th percentile body mass index for age and sex) and 37 normal-weight (< 85th percentile) without personal or family history of diabetes mellitus were enrolled. Subjects were evaluated with an oral glucose tolerance test, metabolic markers, resting energy expenditure, Tanner staging, and (31)P magnetic resonance spectroscopy of skeletal muscle for mitochondrial function.. Overweight and normal-weight children showed no difference in muscle ATP synthesis [phosphocreatine (PCr) recovery after exercise] (32.4 +/- 2.3 vs. 34.1 +/- 2.1, P = 0.58). However, insulin-resistant children had significantly prolonged PCr recovery when compared with insulin-sensitive children, by homeostasis model assessment for insulin resistance quartile (ANOVA, P = 0.04). Similarly, insulin-resistant overweight children had PCr recovery that was prolonged compared with insulin-sensitive overweight children (P = 0.01). PCr recovery was negatively correlated with resting energy expenditure in multivariate modeling (P = 0.03). Mitochondrial function worsened during mid-puberty in association with insulin resistance.. Reduced skeletal muscle mitochondrial oxidative phosphorylation, assessed by PCr recovery, is associated with insulin resistance and an altered metabolic phenotype in children. Normal mitochondrial function may be associated with a healthier metabolic phenotype in overweight children. Further studies are needed to investigate the long-term physiological consequences and potential treatment strategies targeting children with reduced mitochondrial function.

Topics: Adolescent; Body Weight; Calorimetry, Indirect; Child; Dyslipidemias; Energy Metabolism; Feeding Behavior; Female; Glycemic Index; Humans; Insulin; Insulin Resistance; Lipids; Magnetic Resonance Spectroscopy; Male; Mitochondria; Obesity; Overweight; Phenotype; Phosphocreatine; Puberty; Surveys and Questionnaires

Mitochondrial activity is altered in skeletal muscle of obese, insulin-resistant or type 2 diabetic patients. We hypothesized that this situation was associated with profound adaptations in resting muscle energetics. For that purpose, we used in vivo (31)P-nuclear magnetic resonance ((31)P-NMR) in male sedentary Wistar rats fed with obesogenic diets known to induce alterations in muscle mitochondrial activity.. Two experimental diets (high sucrose and high fat) were provided for 6 weeks at two levels of energy (standard, N and high, H) and compared to control diet. The rates of the adenosine triphosphate (ATP) exchange between phosphocreatine (PCr) and gamma-ATP (k(a)) and beta-adenosine diphosphate (beta-ADP) to beta-ATP (k(b)) were evaluated using (31)P-NMR in resting gastrocnemius muscle. Muscle contents in phosphorylated compounds as well as creatine, were assessed using (31)P-NMR and biochemical assays, respectively.. ATP content increased by 6.7-8.5% in standard-energy high-sucrose (NSU), high-energy high-fat (HF) and high-energy high-sucrose (HSU) groups compared to control (P < 0.05), whereas PCr content decreased by 4.2-6.4% (P < 0.01). Consequently, PCr to ATP ratio decreased in NSU, HF, and HSU groups, compared to control (P < 0.01). Furthermore in high-energy groups (HF and HSU) compared to control, creatine contents were decreased by 14-19% (P < 0.001), whereas k(a) and k(b) fluxes were increased by 89-133% (P < 0.001) and 243-277% (P < 0.01), respectively.. Our in vivo data showed adaptations of resting skeletal muscle energetics in response to high-energy diets. Increased activity of enzymes catalyzing ATP production may reflect a compensatory mechanism to face impaired mitochondrial ATP synthesis in order to preserve intracellular energy homeostasis.

Topics: Adaptation, Physiological; Adenosine Diphosphate; Adenosine Triphosphate; Animals; Dietary Fats; Dietary Sucrose; Disease Models, Animal; Energy Metabolism; Hydrogen-Ion Concentration; Kinetics; Magnetic Resonance Spectroscopy; Male; Mitochondria, Muscle; Muscle, Skeletal; Obesity; Phosphocreatine; Phosphorus Isotopes; Rats; Rats, Wistar

Mitochondrial dysfunction and increased intramyocellular lipid (IMCL) content have both been implicated in the development of insulin resistance and type 2 diabetes mellitus, but the relative contributions of these two factors in the aetiology of diabetes are unknown. As obesity is an independent determinant of IMCL content, we examined mitochondrial function and IMCL content in overweight type 2 diabetes patients and BMI-matched normoglycaemic controls.. In 12 overweight type 2 diabetes patients and nine controls with similar BMI (29.4 +/- 1 and 29.3 +/- 0.9 kg/m(2) respectively) in vivo mitochondrial function was determined by measuring phosphocreatine recovery half-time (PCr half-time) immediately after exercise, using phosphorus-31 magnetic resonance spectroscopy. IMCL content was determined by proton magnetic resonance spectroscopic imaging and insulin sensitivity was measured with a hyperinsulinaemic-euglycaemic clamp.. The PCr half-time was 45% longer in diabetic patients compared with controls (27.3 +/- 3.5 vs 18.7 +/- 0.9 s, p < 0.05), whereas IMCL content was similar (1.37 +/- 0.30 vs 1.25 +/- 0.22% of the water resonance), and insulin sensitivity was reduced in type 2 diabetes patients (26.0 +/- 2.2 vs 18.9 +/- 2.3 mumol min(-1) kg(-1), p < 0.05 [all mean +/- SEM]). PCr half-time correlated positively with fasting plasma glucose (r (2) = 0.42, p < 0.01) and HbA(1c) (r (2) = 0.48, p < 0.05) in diabetic patients.. The finding that in vivo mitochondrial function is decreased in type 2 diabetes patients compared with controls whereas IMCL content is similar suggests that low mitochondrial function is more strongly associated with insulin resistance and type 2 diabetes than a high IMCL content per se. Whether low mitochondrial function is a cause or consequence of the disease remains to be investigated.

Topics: Aged; Blood Glucose; Body Mass Index; Case-Control Studies; Diabetes Mellitus, Type 2; Humans; Insulin; Insulin Resistance; Lipid Metabolism; Magnetic Resonance Spectroscopy; Male; Middle Aged; Mitochondria, Muscle; Muscle, Skeletal; Obesity; Phosphocreatine; Phosphorus Isotopes

To determine whether skeletal muscle energetics, measured by in vivo (31)P-nuclear magnetic resonance spectroscopy during plantar flexion exercise, differ between multiethnic, prepubertal girls with or without a predisposition to obesity.. Cross-sectional study.. Girls (mean age and body fat+/-s.d.=8.6+/-0.3 y and 22.6+/-4.2%) were recruited according to parental leanness or obesity defined as follows: LN (n=22), two lean parents, LNOB (n=18), one lean and one obese parent; and OB (n=15), two obese parents.. A 3 min, rest-exercise-recovery plantar flexion protocol was completed. Work was calculated from the force data. Spectra were analyzed for inorganic intracellular phosphate (P(i)), phosphocreatine (PCr), P(i)/PCr (ratio of the low and high energy phosphates indicating the bioenergetic state of the cell), intracellular pH, and adenosine triphosphate (ATP). Magnetic resonance imaging was used to determine calf muscle volume.. BMI was lower in the girls in the LN group (15.9+/-1.5 kg/m(2)) compared to the OB group (16.7+/-1.3 kg/m(2)) of girls (P<0.05), with no difference with the LNOB group (16.7+/-1.9 kg/m(2)). Adjusted for muscle volume and cumulative work, no differences in P(i), PCr, P(i)/PCr, pH, or ATP were observed among the LN, LNOB and OB groups at rest, the end of exercise, and after 60 and 300 s of recovery. From rest to the end of exercise, P(i) and P(i)/PCr (mean+/-s.d.: 0.2+/-0.1 vs 1.5+/-1.0) increased, whereas PCr and pH (7.04+/-0.06 vs 6.95+/-0.10) decreased (all P<0.001). By 60 s of recovery, P(i) and P(i)/PCr decreased, whereas PCr and pH increased (all P<0.001).. Skeletal muscle energetics, specifically P(i)/PCr and pH measured during plantar flexion exercise, do not differ between prepubertal girls with or without a familial predisposition to obesity.

Topics: Body Composition; Body Mass Index; Calorimetry, Indirect; Child; Cross-Sectional Studies; Energy Metabolism; Exercise; Female; Genetic Predisposition to Disease; Humans; Hydrogen-Ion Concentration; Magnetic Resonance Imaging; Muscle, Skeletal; Obesity; Oxygen Consumption; Parents; Phosphates; Phosphocreatine; Phosphorus Isotopes

The use of magnetic resonance spectroscopy (MRS) to monitor cellular bioenergetics during weight loss may provide novel insights regarding metabolic functioning.. Changes were noted in 18 sedentary, moderately overweight women following a 7-week program consisting of a low-fat, 422-428 MJ/day (1010-1025 kcal/day) diet, a progressive walking program, a vitamin-mineral-fortified, isolated-protein meal supplement drink and a weekly group meeting. Mitochondrial energy production and utilization were assessed by measuring the concentrations of inorganic phosphate (Pi) and phosphocreatine (PCr) through magnetic resonance spectroscopy. Anthropometric changes were also monitored.. Dietary analysis of subjects' pre-intervention food records showed intakes of numerous vitamins and minerals below 100% of the Recommended Dietary Allowances (RDA), most commonly for folic acid, vitamin E, magnesium, iron and zinc. Relative to pre-intervention levels, final measurements showed that all women lost body weight, ranging from 2.6 to 10.0 kg. Body mass index declined in all subjects, from 0.55 to 3.86 kg/m2. All subjects lost fat mass, ranging from 0.9 to 10.4 kg. Seventeen of 18 women showed a decline in their percentage of body fat, ranging from 2.3 to 10.1%. Twelve of 18 subjects showed an increase of 0.1-3.5 kg of fat-free mass, with half of these values increasing by > 1.0 kg. No changes from baseline levels were found in the Pi/PCr ratio over 7 weeks under resting, exercise or recovery conditions, suggesting a preservation in muscle energy function over the course of the study while the subjects were losing fat mass and total body weight.. The possible metabolic advantage associated with a program that employs moderate energy restriction, repletion of vitamin and mineral intakes to RDA levels, and a regular aerobic exercise program is proposed.

Topics: Adipose Tissue; Adult; Anthropometry; Body Composition; Diet, Reducing; Energy Metabolism; Exercise; Female; Food, Formulated; Humans; Magnetic Resonance Spectroscopy; Mitochondria, Muscle; Obesity; Phosphates; Phosphocreatine; Phosphorus; Weight Loss

The purpose of this study was to investigate the energetic metabolism in obese Zucker rats, using phosphorus nuclear magnetic resonance spectroscopy at rest and during a 2-Hz muscle stimulation and subsequent recovery. Animals were anesthetized with ketamine (150 mg/kg ip). Fed obese rats and 2-day-fasted obese rats were compared with their normally fed and 2-day-fasted lean litter mates. No differences were found between the two groups for ATP, total creatine, phosphocreatine (PCr), and intracellular pH. Starvation in lean rats resulted in a significant fall in inorganic phosphate (Pi), increased resting ADP level, and decreased PCr and ADP recovery after stimulation. The obese rats exhibited a decreased PCr/Pi and increased ADP at rest and a decreased PCr resynthesis and ADP metabolization rate after stimulation. Muscle stimulation in fasted obese rats induced higher PCr depletion and more pronounced acidosis. These results suggest an in vivo mitochondrial metabolism dysfunction in fasted lean as well as in fed and fasted obese rats.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Analysis of Variance; Animals; Electric Stimulation; Energy Metabolism; Female; Magnetic Resonance Spectroscopy; Muscle Contraction; Muscles; Obesity; Phosphates; Phosphocreatine; Rats; Rats, Zucker

Most of the energy required for muscle contraction is generated by the splitting of ATP. Catabolism of carbohydrates to pyruvate and lactate by glycolysis (anaerobic) produces ATP needed during exercise of high intensity and short duration but the energy release is incomplete. The first step in the release of the remaining energy is the conversion of pyruvate to acetyl-CoA which is also formed from the oxidation of fatty acids particularly during sustained exercise. Acetyl-CoA is next oxidized in the tricarboxylic acid cycle producing the reduced forms of pyridine and flavin nucleotides. The hydrogens of the reduced nucleotides are transported in the form of electrons through the electron transport (respiratory) chain to molecular O2 to form H2O. The resulting free energy change is used to phosphorylate ADP to ATP. Enzymes of fatty acid oxidation, tricarboxylic acid cycle and respiration are located inside mitochondria. Energy status of cells can be described by the relative concentrations of adenine nucleotides (ATP, ADP and AMP) since the nucleotides act as allosteric modifiers of several key enzymes of energy metabolism. Energy is expended to synthesize and store fuel nutrients in utilizable forms (glycogen, triglycerides and proteins) and to maintain the storage forms in a dynamic steady state. The energy cost of such postprandial metabolic processes is defined as the "thermic" effect of food. Storage of dietary carbohydrates as adipose tissue triglycerides expends more energy than that of dietary fats. Overfeeding of certain individuals is known to burn more energy over and above that expected from the "thermic" effect and the process is referred to as "luxus consumption."(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine Triphosphate; Cells; Citric Acid Cycle; Energy Metabolism; Enzymes; Fatty Acids; Glycolysis; Humans; Mitochondria; Obesity; Oxidation-Reduction; Oxidative Phosphorylation; Phosphocreatine; Physical Exertion

Using experimental models of various disease states, the ability of the isolated perfused working rat heart to withstand and recover from a period of severe ischemia was investigated. The results revealed that the coexistence of a diabetic state, obesity, or left ventricular hypertrophy increased the susceptibility of the hearts to ischemic damage and reduced the rate or the extent of postischemic recovery. In contrast, hearts obtained from moderately hypertensive rats exhibited a greater resistance to, and a superior recovery from, ischemia than did hearts obtained from normotensive controls.

Topics: Adenosine Triphosphate; Animals; Cardiac Output; Cardiomegaly; Coronary Circulation; Coronary Disease; Diabetes Mellitus, Experimental; Disease Models, Animal; Electrolytes; Heart Arrest, Induced; Hypertension; Male; Myocardial Contraction; Myocardium; Obesity; Phosphocreatine; Procaine; Rats; Triglycerides