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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The treatment of obesity in companion animals frequently focuses on restriction of energy intake. One important question with this treatment is whether dietary energy restriction (ER) produces a sustained decrease in mass-adjusted energy expenditure (EE), which prevents further weight loss and promotes rapid regain of body weight during lapses in dietary ER. This review summarizes studies that investigated the effects of dietary ER on EE at the whole-animal, organ, and cellular level. Whole-animal studies indicate that long-term dietary ER either decreases or does not affect mass-adjusted EE. The reason for this discrepancy between studies is not entirely clear, although analysis of data pooled from multiple studies suggests that a reduction in mass-adjusted EE with long-term ER would be observed if the sample size were sufficiently large and appropriate methods were used to adjust EE for body size. At the organ level, attempts were made to determine whether alterations in organ mass can entirely explain changes in EE with dietary ER. However, these studies were not conclusive, and it remains to be determined whether changes in EE exceed those that would be predicted from ER-induced alterations in organ mass. At the cellular level, there is evidence that dietary ER may induce sustained decreases in substrate oxidation, mitochondrial proton, and Na+-K+-ATPase activity in at least some tissues. These results are consistent with the idea that dietary ER may induce decreases in cellular EE. However, future studies integrating measurements at the whole-animal, organ, and cellular level will be required to determine definitively whether dietary ER produces sustained decreases in tissue or cellular EE.
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PMID:Energy expenditure and restriction of energy intake: could energy restriction alter energy expenditure in companion animals? 1677 68

In spite of a progressive fall in the incidence of traditional risk factors of cardiovascular morbidity (cigarette smoking, high blood pressure, and hyperlipidemia), there is an upward trend in the prevalence of obesity and chronic kidney disease (CKD). Furthermore, there is a strong correlation between body mass indices and the relative risk of progression of CKD. The close biophysiological interaction between obesity and CKD is evident by a similar occurrence of comorbidities including insulin resistance, hyperlipidermia, endothelial dysfunction, and sleep disorders. Truncal obesity is a primary component of metabolic syndrome; unlike peripheral fat, the visceral adipocytes are more resistant to insulin. In addition, lipolysis results in a release of free fatty acid and TG, whereas hypertriglycedemia is potentiated by uremic activation of fatty acid synthase. Hypertriglycedemia and low HDL cholesterol increase the relative risk of progression of CKD. Furthermore, endothelial inflammation and premature atherosclerosis are promoted by hyperhomocysteinemia and oxidation of LDL, both of which are commonly observed in CKD and obesity. Predominance of oxidative stress in both obesity and azotemia stimulate synthesis of angiotensin II, which in turn increases TGF-B and plasminogen activator inhibitor-1, thereby propagating glomerular fibrosis. Furthermore, local synthesis of angiotensinogen by adipocytes, leptin activation of sympathetic nervous system, and hyperinsulinemia contribute to the development of hypertension in obesity and CKD. In addition, increased renal tubular expression of Na-K-ATPase and a blunted response to natiuretic hormones in obesity promote salt and water retention. Glomerular hyperfiltration from systemic volume load and hypertension results in mesangial cellular proliferation and progressive renal fibrosis. In addition, maternal nutritional deprivation increases the incidence of obesity, hypertension, and diabetes in adulthood. Reduced fetal protein synthesis contributes to oxidative glomerular injury and impairment of renal morphogenesis. Thus, kidneys are poorly equipped to handle physiologic stress that may result from the rapid body growth and programmed metabolic dysfunction later in life. Finally, in order to minimize morbidity of obesity-related kidney disease, preventive strategy must include optimal maternal health care, promotion of healthy nutrition and routine physical exercise, and early detection of CKD.
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PMID:The role of obesity and its bioclinical correlates in the progression of chronic kidney disease. 1704 21

Oxidative stress may play a role in the pathogenic mechanism of essential hypertension. Lipid peroxidation can alter the cellular structure of membrane-bound enzymes by changing the membrane phospholipids fatty acids composition. We investigated the relationship between (Na + K)-ATPase activity, lipid peroxidation, and erythrocyte fatty acid composition in essential hypertension. The study included 40 essential hypertensive and 49 healthy normotensive men (ages 35-60 years). Exclusion criteria were obesity, dyslipidemia, diabetes mellitus, smoking, and any current medication. Patients underwent 24-h ambulatory blood pressure monitoring and blood sampling. Lipid peroxidation was measured in the plasma and erythrocytes as 8-isoprostane or malondialdehyde (MDA), respectively. Antioxidant capacity was measured as ferric reducing ability of plasma (FRAP) in the plasma and as reduced/oxidized glutathione (GSH/GSSG ratio) in erythrocytes. (Na + K)-ATPase activity and fatty acids were determined in erythrocyte membranes. Hypertensives had higher levels of plasma 8-isoprostane, erythrocyte MDA, and relative percentage of saturated membrane fatty acids, but lower plasma FRAP levels, erythrocyte GSH/GSSG ratio, (Na + K)-ATPase activity and relative percentage of unsaturated membrane fatty acids, compared with normotensives. Day-time systolic and diastolic blood pressures correlated positively with lipid peroxidation parameters, but negatively with (Na + K)-ATPase activity. These findings suggest that the modulation of (Na + K)-ATPase activity may be associated with changes in the fatty acid composition induced by oxidative stress and provide evidence of a role for this enzyme in the pathophysiology of essential hypertension.
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PMID:Relationship between (Na + K)-ATPase activity, lipid peroxidation and fatty acid profile in erythrocytes of hypertensive and normotensive subjects. 1741 Apr 6

The sodium(Na)- and potassium(K)-activated adenosine-triphosphatase (Na,K-ATPase) is a membrane enzyme that energizes the Na-pump by hydrolysing adenosine triphosphate and wasting energy as heat, so playing a role in thermogenesis and energy balance. Na,K-ATPase regulation by insulin is controversial; in tissue of hyperglycemic-hyperinsulinemic ob/ob mice, we reported a reduction, whereas in streptozotocin-treated hypoinsulinemic-diabetic Swiss and ob/ob mice we found an increased activity, which is against a genetic defect and suggests a regulation by hyperinsulinemia. In human adipose tissue from obese patients, Na,K-ATPase activity was reduced and negatively correlated with body mass index, oral glucose tolerance test-insulinemic area and blood pressure. We hypothesized that obesity is associated with tissue Na,K-ATPase reduction, apparently linked to hyperinsulinemia, which may repress or inactivate the enzyme, thus opposing thyroid hormones and influencing thermogenesis and obesity development. Insulin action on Na,K-ATPase, in vivo, might be mediated by the high level of non-esterified fatty acids, which are circulating enzyme inhibitors and increase in obesity, diabetes and hypertension. In this paper, we analyse animal and human tissue Na,K-ATPase, its level, and its regulation and behaviour in some hyperinsulinemic and insulin-resistant states; moreover, we discuss the link of the enzyme with non-esterified fatty acids and attempt to interpret and organize in a coherent view the whole body of the exhaustive literature on this complicated topic.
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PMID:Animal and human tissue Na,K-ATPase in normal and insulin-resistant states: regulation, behaviour and interpretative hypothesis on NEFA effects. 1744 65

Carpenter syndrome is a pleiotropic disorder with autosomal recessive inheritance, the cardinal features of which include craniosynostosis, polysyndactyly, obesity, and cardiac defects. Using homozygosity mapping, we found linkage to chromosome 6p12.1-q12 and, in 15 independent families, identified five different mutations (four truncating and one missense) in RAB23, which encodes a member of the RAB guanosine triphosphatase (GTPase) family of vesicle transport proteins and acts as a negative regulator of hedgehog (HH) signaling. In 10 patients, the disease was caused by homozygosity for the same nonsense mutation, L145X, that resides on a common haplotype, indicative of a founder effect in patients of northern European descent. Surprisingly, nonsense mutations of Rab23 in open brain mice cause recessive embryonic lethality with neural-tube defects, suggesting a species difference in the requirement for RAB23 during early development. The discovery of RAB23 mutations in patients with Carpenter syndrome implicates HH signaling in cranial-suture biogenesis--an unexpected finding, given that craniosynostosis is not usually associated with mutations of other HH-pathway components--and provides a new molecular target for studies of obesity.
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PMID:RAB23 mutations in Carpenter syndrome imply an unexpected role for hedgehog signaling in cranial-suture development and obesity. 1750 33

Na,K-ATPase is the active transporter that maintains Na+ and K+ gradients across the cell membrane. The enzyme is composed of Alpha and Beta subunits and there are four Alpha and three Beta subunit isoforms. The enzyme is responsible for various physiological processes including housekeeping function of animal cells, and specific function has been allocated to each isoform during evolution. We found that the Na,K-ATPase Alpha2 subunit functions in concert with various transporters during ontogeny by analyses of phenotypes of mice with defective Alpha2 subunit. The homozygous mice die soon after birth without breathing and the heterozygous mice show late-onset obesity. We summarize here the specific functions of the Na,K-ATPase Alpha2 subunit and physiological roles in vivo.
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PMID:Modulation of neural activities by Na, K-ATPase alpha 2 subunit through functional coupling with transporters. 1753 42

We examined the role of epidermal growth factor (EGF) receptor in the pathogenesis of leptin-induced hypertension in the rat. Leptin, administered in increasing doses (0.1-0.5 mg/kg/day) for 10 days, increased phosphorylation levels of non-receptor tyrosine kinase, c-Src, EGF receptor and extracellular signal-regulated kinases (ERK) in aorta and kidney, which was accompanied by the increase in plasma concentration and urinary excretion of isoprostanes and H2O2. Blood pressure and renal Na+,K+-ATPase activity were higher, whereas urinary sodium excretion was lower in animals receiving leptin. The effects of leptin on renal Na+,K+-ATPase, natriuresis and blood pressure were abolished by NADPH oxidase inhibitor, apocynin, Src kinase inhibitor, PP2, EGF receptor inhibitor, AG1478, protein farnesyltransferase inhibitor, manumycin A, and ERK inhibitor, PD98059. In contrast, inhibitors of insulin-like growth factor-1 and platelet-derived growth factor receptors, AG1024 and AG1295, respectively, only slightly reduced ERK phosphorylation and had no effect on blood pressure in rats receiving leptin. These data indicate that: (1) experimental hyperleptinemia is associated with oxidative stress and c-Src-dependent transactivation of the EGF receptor, which stimulates ERK in vascular wall and the kidney, (2) overactivity of EGF receptor-ERK pathway contributes to leptin-induced hypertension by stimulating renal Na+,K+-ATPase and reducing sodium excretion, (3) inhibitors of c-Src, EGF receptor and ERK may be considered as a novel therapy for hypertension associated with hyperleptinemia, e.g. in patients with obesity and metabolic syndrome.
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PMID:Transactivation of epidermal growth factor receptor in vascular and renal systems in rats with experimental hyperleptinemia: role in leptin-induced hypertension. 1828 56

Obesity is a complex multifactorial disorder that is often associated with cardiovascular diseases. Research on experimental models has suggested that cardiac dysfunction in obesity might be related to alterations in myocardial intracellular calcium (Ca2+) handling. However, information about the expression of Ca2+-related genes that lead to this abnormality is scarce. We evaluated the effects of obesity induced by a high-fat diet in the expression of Ca2+-related genes, focusing the L-type Ca2+ channel (Cacna1c), sarcolemmal Na+/Ca2+ exchanger (NCX), sarcoplasmic reticulum Ca2+ ATPase (SERCA2a), ryanodine receptor (RyR2), and phospholamban (PLB) mRNA in rat myocardium. Male 30-day-old Wistar rats were fed a standard (control) or high-fat diet (obese) for 15 weeks. Obesity was defined as increased percent of body fat in carcass. The mRNA expression of Ca2+-related genes in the left ventricle was measured by RT-PCR. Compared with control rats, the obese rats had increased percent of body fat, area under the curve for glucose, and leptin and insulin plasma concentrations. Obesity also caused an increase in the levels of SERCA2a, RyR2 and PLB mRNA (P < 0.05) but did not modify the mRNA levels of Cacna1c and NCX. These findings show that obesity induced by high-fat diet causes cardiac upregulation of Ca2+ transport_related genes in the sarcoplasmic reticulum.
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PMID:Obesity induces upregulation of genes involved in myocardial Ca2+ handling. 1871 44

The aim was to investigate low-density lipoprotein (LDL) composition and Na(+)/K(+) adenosine triphosphatase (ATPase) and Ca(2+) ATPase activities and membrane fluidity measured by 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH) in platelets from obese patients and controls in order to identify, if any, platelet membrane's chemical-physical and/or functional modifications associated with compositional modification of circulating lipoproteins. Moreover, we studied the in vitro effect on both platelet transmembrane cationic transport and fluidity, by incubating LDL from 30 obese subjects with platelets from 30 control subjects. The analysis of the chemical composition of LDL from obese patients showed a significant increase in the percent content of total cholesterol (TC) and triglycerides (TGs) and in the mean levels of lipid hydroperoxides compared to controls' LDL. Platelet Na(+)/K(+) ATPase and Ca(2+) ATPase activities showed, respectively, a significant decrease and increase in patients compared to controls; minor significant, respectively, decreases and increases are shown also in control platelets incubated with LDL from obese patients. Anisotropy tested with TMA-DPH probe was significantly increased both in platelets from obese patients and in control platelets incubated with LDL from obese patients compared to control platelets. This study highlights that obesity induces remarkable modifications both in lipoproteins and platelets. Both platelet hyperfunction and quantitative/qualitative alterations in plasma lipoproteins, as well as an altered interaction between circulating lipoproteins and platelets, might play a relevant role in the increased prevalence of the early atherosclerotic lesions development in obese subjects. The present data point out that obesity might represent a major potentially modifiable risk factor for the onset of numerous complications, in particular cardiovascular ones.
Obesity (Silver Spring) 2009 Jul
PMID:Interactions between lipoproteins and platelet membranes in obesity. 1919 63

P4 ATPases (type 4 P-type ATPases) are multispan transmembrane proteins that have been implicated in phospholipid translocation from the exoplasmic to the cytoplasmic leaflet of biological membranes. Studies in Saccharomyces cerevisiae have indicated that P4 ATPases are important in vesicle biogenesis and are required for vesicular trafficking along several intracellular vesicular transport routes. Although little is known about mammalian P4 ATPases, some members of this subfamily appear to be associated with human disease or mouse pathophysiology. ATP8B1, a phosphatidylserine translocase, is the most extensively studied mammalian P4 ATPase. This protein is important for maintaining the detergent resistant properties of the apical membrane of the hepatocyte. Mutations in ATP8B1 give rise to severe liver disease. Furthermore, a role for Atp8b3 in mouse sperm cell capacitation has been suggested, whereas deficiency of Atp10a and Atp10d leads to insulin resistance and obesity in mice. Here we review the present status on the pathophysiological consequences of P4 ATPase deficiency.
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PMID:P4 ATPases - lipid flippases and their role in disease. 1925 79


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