Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.21 (CPT)
 4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Unequivocal demarcation between immature, nonmigratory yellow eels and migratory silver eels of greater sexual maturity is possible by measuring eye diameter and retinal capillary length, which undergo a 1.5- and 2.3-fold increase during metamorphosis, respectively. Anatomical arrangement of trunk musculature is similar in the two groups except for an increased depth of slow muscle in silver eel. Histochemical analysis reveals a progressive increase in numbers of "displaced" fast fibres within slow muscle of the lateral line triangle in maturing eels, although these are unlikely to affect recruitment pattern of muscle fibre types. Previous studies have suggested greater involvement of fast muscle in locomotion of migratory eels. In contrast, estimates of enzyme activity in fast muscle suggest an inadequate aerobic capacity to fuel sustained activity. Myoglobin content is extremely low, around 0.4 nM g wet wt-1. Prolonged anaerobic metabolism is also discounted as a migratory strategy. Increased energy provision for migration is apparently derived from increased capacity for both aerobic carbohydrate metabolism and mitochondrial fatty acid oxidation within slow muscle of silver eels. Activity of hexokinase (HK) shows a 1.6-fold increase (to 0.51 microM g wet wt-1) and carnitine palmitoyltransferase (CPT) a 3.1-fold increase (to 0.22 microM g wet wt-1 min-1), suggesting a maximal flux through these pathways of 18 and 14 ATP equivalents, respectively. However, the fatty acyl transferase system of skeletal muscle mitochondria displays up to threefold greater activity with palmitoleoyl CoA (C16:1) as substrate than with the usual palmitoyl CoA (C16:0). Slow muscle of silver eel is therefore capable of deriving aerobic energy from free fatty acids and carbohydrate in the ratio 2.3:1. Differences in aerobic enzyme activities are not paralleled by myoglobin content of slow muscle, being 15 and 16 nM g wet wt-1 for yellow and silver eel, respectively. Structural reorganization of muscle fibres during metamorphosis, however, results in a twofold elevation of cytoplasmic myoglobin concentration in silver eel. It would appear that dramatic differences in metabolic capacity between life history stages of eel is required to overcome locomotory inefficiency of yellow eels and to "preadapt" silver eels for migratory activity. This increased locomotory capacity may be amplified by a subsequent training response.
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PMID:Metamorphosis of the American eel, Anguilla rostrata LeSeur: I. Changes in metabolism of skeletal muscle. 395 May 63

A potential role for fatty acid metabolism in the regulation of energy balance in the brain or in the periphery has been considered only recently. Fatty acid synthase (FAS) catalyzes the synthesis of long-chain fatty acids, whereas the breakdown of fatty acids by beta-oxidation is regulated by carnitine palmitoyltransferase-1, the rate-limiting enzyme for the entry of fatty acids into the mitochondria for oxidation. While the question of the physiological role of fatty acid metabolism remains to be resolved, studies indicate that inhibition of FAS or stimulation of carnitine palmitoyltransferase-1 using cerulenin or synthetic FAS inhibitors reduces food intake and incurs profound and reversible weight loss. Several hypotheses regarding the mechanisms by which these small molecules mediate their effects have been entertained. Centrally, these compounds alter the expression of hypothalamic neuropeptides, generally reducing the expression of orexigenic peptides. Whether through central, peripheral, or combined central and peripheral mechanisms, these compounds also increase energy consumption to augment weight loss. In vitro and in vivo studies indicate that at least part of C75's effects is mediated by modulation of adenosine monophosphate-activated protein kinase, a member of an energy-sensing kinase family. These compounds, with chronic treatment, also alter gene expression peripherally to favor a state of enhanced energy consumption. Together, these effects raise the possibility that pharmacological alterations in fatty acid synthesis/degradation may serve as a target for obesity therapeutics.
Obesity (Silver Spring) 2006 Aug
PMID:Fatty acid metabolism, the central nervous system, and feeding. 1702 67

Beta-Aminoisobutyric acid (BAIBA), a thymine catabolite, increases fatty acid oxidation (FAO) in liver and reduces the gain of body fat mass in Swiss (lean) mice fed a standard chow. We determined whether BAIBA could prevent obesity and related metabolic disorders in different murine models. To this end, BAIBA (100 or 500 mg/kg/day) was administered for 4 months in mice totally deficient in leptin (ob/ob). BAIBA (100 mg/kg/day) was also given for 4 months in wild-type (+/+) mice and mice partially deficient in leptin (ob/+) fed a high-calorie (HC) diet. BAIBA did not limit obesity and hepatic steatosis in ob/ob mice, but reduced liver cytolysis and inflammation. In ob/+ mice fed the HC diet, BAIBA fully prevented, or limited, the gain of body fat, steatosis and necroinflammation, glucose intolerance, and hypertriglyceridemia. Plasma beta-hydroxybutyrate was increased, whereas expression of carnitine palmitoyltransferase-1 was augmented in liver and white adipose tissue. Acetyl-CoA carboxylase was more phosphorylated, and de novo lipogenesis was less induced in liver. These favorable effects of BAIBA in ob/+ mice were associated with a restoration of plasma leptin levels. The reduction of body adiposity afforded by BAIBA was less marked in +/+ mice. Finally, BAIBA significantly stimulated the secretion of leptin in isolated ob/+ adipose cells, but not in +/+ cells. Thus, BAIBA could limit triglyceride accretion in tissues through a leptin-dependent stimulation of FAO. As partial leptin deficiency is not uncommon in the general population, supplementation with BAIBA may help to prevent diet-induced obesity and related metabolic disorders in low leptin secretors.
Obesity (Silver Spring) 2008 Sep
PMID:Beta-aminoisobutyric acid prevents diet-induced obesity in mice with partial leptin deficiency. 1918 30

No specific treatment for nonalcoholic hepatic fatty liver disease has been defined. We followed the spontaneous evolution of liver steatosis and tested the therapeutic usefulness of metformin and fenofibrate in a model of steatosis, the Zucker diabetic fatty (ZDF) rat. ZDF and control rats were studied at 7, 14, and 21 weeks. After initial study at 7 weeks, ZDF rats received no treatment, metformin or fenofibrate until studies at 14 or 21 weeks. ZDF rats were obese, hypertriglyceridemic, insulin resistant at 7 weeks, type 2 diabetic at 14, diabetic with insulin deficiency at 21. They had steatosis at 7 weeks with increased hepatic expression and activity of lipogenesis. Steatosis was unchanged at 14 and 21 weeks despite lower expression and activity of lipogenesis. Metformin and fenofibrate did not modify energy intake or expenditure or the evolution of diabetes. Both compounds decreased plasma triacylglycerol (TAG) concentrations. Hepatic TAG content was reduced by fenofibrate at 14 and 21 weeks but only at 21 weeks by metformin. Metformin had no significant effects on the expression in liver of genes of fatty acids metabolism. The beneficial effect of fenofibrate occurred despite increased expression of genes involved in the uptake and activation of fatty acids. Acyl-CoA oxidase (ACO) and carnitine palmitoyltransferase I (CPTI) mRNA levels were increased by fenofibrate showing evidence of increased lipid oxidation. To conclude, metformin had only moderate effects on liver steatosis. The effects of fenofibrate was more marked but remained mild.
Obesity (Silver Spring) 2009 Jul
PMID:Nonalcoholic hepatic steatosis in Zucker diabetic rats: spontaneous evolution and effects of metformin and fenofibrate. 1955 25

Skeletal muscle fat is greater in African ancestry individuals compared with whites, is associated with diabetes, and is a heritable polygenic trait. However, specific genetic factors contributing to skeletal muscle fat in humans remain to be defined. Muscle carnitine palmitoyltransferase-1B (CPT1B) is a key enzyme in the regulation of skeletal muscle mitochondrial beta-oxidation of long-chain fatty acids, and as such is a reasonable biological candidate gene for skeletal muscle fat accumulation. Therefore, we examined the association of three nonsynonymous coding variants in CPT1B (G531L, I66V, and S427C; a fourth, A320G, could not be genotyped) and quantitative computed tomography measured tibia skeletal muscle composition and BMI among 1,774 Afro-Caribbean men aged > or =40, participants of the population-based Tobago Health Study. For all variants, no significant differences were observed for BMI or total adipose tissue. Among individuals who were homozygous for the minor allele at G531L or I66V, intermuscular adipose tissue (IMAT) was 87% (P = 0.03) and 54% lower (P = 0.03), respectively. In contrast, subcutaneous adipose tissue (SAT) was 11% (P = 0.017) and 7% (P = 0.049) higher, respectively, than among individuals without these genotypes. These associations were independent of age, body size, and muscle area. Finally, no individuals with type 2 diabetes were found among those who were homozygous for the minor allele of either at G531L and I66V whereas 14-18% of men with the major alleles had type 2 diabetes (P = 0.03 and 0.007, respectively). Our results suggest a novel association between common nonsynonymous coding variants in CPT1B and ectopic skeletal muscle fat among middle-aged and older African ancestry men.
Obesity (Silver Spring) 2009 Jul
PMID:Association of the CPT1B gene with skeletal muscle fat infiltration in Afro-Caribbean men. 1955 26

The standard treatment of partial-thickness burns includes topical silver products such as silver sulfadiazine (SSD) cream and enclosed dressings including silver-impregnated foam (Mepilex Ag; Molnlycke Health Care, Gothenburg, Sweden) and silver-laden sheets (Aquacel Ag; ConvaTec, Skillman, NJ). The current state of health care is limited by resources, with an emphasis on evidence-based outcomes and cost-effective treatments. This study includes a decision analysis with an incremental cost-utility ratio comparing enclosed silver dressings with SSD in partial-thickness burn patients with TBSA less than 20%. A comprehensive literature review was conducted to identify clinically relevant health states in partial-thickness burn patients. These health states include successful healing, infection, and noninfected delayed healing requiring either surgery or conservative management. The probabilities of these health states were combined with Medicare CPT reimbursement codes (cost) and patient-derived utilities to fit into the decision model. Utilities were obtained using a visual analog scale during patient interviews. Expected cost and quality-adjusted life years (QALYs) were calculated using the roll-back method. The incremental cost-utility ratio for enclosed silver dressing relative to SSD was $40,167.99/QALY. One-way sensitivity analysis of complication rates confirmed robustness of the model. Assuming a maximum willingness to pay $50,000/QALY, the complication rate for SSD must be 22% or higher for enclosed silver dressing to be cost effective. By varying complication rates for SSD and enclosed silver dressings, the two-way sensitivity analysis demonstrated the cost effectiveness of using enclosed silver dressing at the majority of complication rates for both treatment modalities. Enclosed silver dressings are a cost-effective means of treating partial thickness burns.
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PMID:Cost-effectiveness comparison between topical silver sulfadiazine and enclosed silver dressing for partial-thickness burn treatment. 2412 6