Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A weight gain of 20-30% above baseline, induced by gastrostomy overfeeding of subhuman primates or gavage overfeeding of rats, was found to completely suppress voluntary food consumption. When overfeeding was discontinued, body weight and oral intake returned in a coordinated fashion to baseline or "set point" values. This regulatory response could have been due to a circulating peptide that was secreted by adipocytes in proportion to the total body energy store and that mediated satiety at the level of the central nervous system. To search for this factor, a subtractive cDNA cloning strategy was developed, permitting the isolation of primate adipocyte genes with augmented expression in the overfed state. A 1.8-kb cDNA clone prepared by subtraction was found to hybridize to a 5-kb message expressed preferentially in the adipose tissue of overfed macaques and rats. This message, which was restricted in distribution among nonadipose tissues, was also detected in human subcutaneous fat. Candidate genes for satiety factors identified by this approach could be used in further studies of body weight regulation and obesity.
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PMID:Identification of candidate genes for a factor regulating body weight in primates. 226 Jul 25

Data from the First Health and Nutrition Examination Survey (HANES), 1971-1974, were used to examine the relationship between blood pressure and the distribution of subcutaneous body fat in 5506 survey participants, ages 30-59. Triceps and subscapular skinfolds were used as approximations of peripheral and centrally located body fat. The effects of race, sex and age on the obesity-blood pressure relationship were analyzed. Subscapular skinfold was the better predictor of both systolic and diastolic blood pressure in each race-sex group, sharing all of the association of triceps with blood pressure and having significant predictive power unshared by triceps. The slopes of regression of subscapular skinfolds with systolic blood pressure for each race-sex group were not significantly different. A 1 mm increase in skinfold thickness increased the predicted mean systolic blood pressure by 0.63 +/- 0.03 mmHg (F = 519). Mean diastolic blood pressure rose 0.43 +/- 0.02 mmHg per unit increase of skinfold in whites (F = 549), and 0.14 +/- 0.04 mmHg less in blacks (F = 13), indicating a significant racial difference. Age and subscapular skinfold contributed independently to the variability in blood pressure in each race-sex group. These results demonstrate that the blood pressure of middle-aged Americans is more directly associated with centrally deposited body fat. This finding is true across race and sex groups, and is independent of age.
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PMID:Evidence for an increased risk for hypertension with centrally located body fat and the effect of race and sex on this risk. 671 42

The human adipocyte-specific apM-1 gene encodes a secretory protein of the adipose tissue and seems to play a role in the pathogenesis of obesity. A 1.3 kb amount of the proximal promoter region has been cloned and analyzed for the presence of putative transcription factor binding sites. Several binding sites known to be involved in adipogenesis and regulation of adipocyte-specific genes (C/EBP, SREBP) are present. No TATA box, but a classical CCAAT box could be identified. To confirm functionality and cell specificity of the 1.3 kb promoter, a series of 5'-deleted fragments were ligated in front of the luciferase gene and the constructs were transfected into 3T3-L1 adipocytes. The reporter gene was effectively transcribed, as demonstrated by the expression of enzyme activity. The 5'-end of the human cDNA was completed by 5'-RACE-PCR. Several alternative transcription start sites were detected by RNase protection assay and primer extension analysis. In addition, an exon/intron boundary was mapped at the extreme 5'-end of the cDNA sequence. Genomic Southern blotting suggests that the human apM-1 gene is a single copy gene.
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PMID:Identification and characterization of the human adipocyte apM-1 promoter. 976 95

Reduction in overweight and obesity management have been shown to be important in the treatment of diabetes. Even modest weight loss produces important metabolic benefits if maintained over the long term. Thus a pharmacotherapeutic agent that could produce a maintained weight loss, and had a good safety profile, would revolutionize the treatment of type II (non-insulin-dependent) diabetes. Two obesity management agents, orlistat and sibutramine, are expected shortly for the long-term treatment of obesity. These agents have been shown to be effective in 1-2-year-long studies in obese, non-diabetic patients. They produced significant improvements in weight loss compared with placebos. The efficacy of these obesity management agents has also been demonstrated in short-term studies in patients with type II diabetes. As yet, however, few studies have investigated the long-term effects of these treatments in diabetic patients. Obese patients with type II diabetes receiving 12 months of dexfenfluramine therapy showed greater reductions in weight, fasting blood glucose and HbA1c levels than the controls. A 1-year study of orlistat treatment for patients with type II diabetes revealed substantial benefits in glycaemic control, even though weight loss was only moderate. A 1-year treatment with orlistat also substantially prevented the conversion of impaired glucose tolerance into type II diabetes (conversion rate 2.6% in the orlistat group versus 10.4% in the placebo group). Encouraging results have also been reported from studies on orlistat and sibutramine in non-diabetics, with beneficial effects seen for weight loss and other diabetes risk factors. Antiobesity pharmacotherapy therefore appears to offer a realistic option for the prevention of diabetes, although further studies are required to determine its efficacy.
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PMID:Pharmacological intervention: the antiobesity approach. 977 25

A 1:1 matched case-control study was conducted to investigate the risk factors for NIDDM in 1995. A total of 100 pairs of case and controls matched on sex, age and hopital of admission. Bivariate analysis revealed 7 factors significantly associated with NIDDM. Conditional logistic regression analysis showed that 3 of the 7 fectors: obesity, greasy and family history of diabetes were risk factors for NIDDM. That might play important roles in the etiology of NIDDM.
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PMID:[A study on the risk factors of none-insulin-dependent type diabetes mellitus]. 1032 33

Abdominally obese individuals have reduced 24-h plasma GH concentrations. Their normal plasma IGF-I levels may reflect GH hypersensitivity. Alternatively, obesity-associated hyposomatotropism may cause less biological effect in target tissues. We therefore determined whole-body responsiveness to the anabolic effects of GH in abdominally obese (OB) and normal weight (NW) premenopausal women. A 1-h iv infusion of GH or placebo was randomly administered to six NW (body mass index, 21.1 +/- 1.9 kg/m(2)) and six OB (body mass index, 35.5 +/- 1.5 kg/m(2)) women in a cross-over design. Endogenous insulin, glucagon and GH secretion was suppressed by infusion of somatostatin. Whole-body protein turnover was measured using a 10-h infusion of [(13)C]-leucine. GH administration induced a similar plasma GH peak in NW and OB women (49.8 +/- 10.4 vs. 45.1 +/- 5.6 mU/liter). GH, compared with placebo infusion, increased nonoxidative leucine disposal, P < 0.0001) and endogenous leucine appearance (R(a), P = 0.0004) but decreased leucine oxidation (P = 0.0051). All changes were similar in both groups. Accordingly, whole-body GH responsiveness, defined as the maximum response of nonoxidative leucine disposal, leucine R(a), and oxidation per unit of GH, was not different in OB and NW women (0.25 +/- 0.18 vs. 0.19 +/- 0.17 micro mol/kg.h, 0.21 +/- 0.23 vs. 0.13 +/- 0.17 micro mol/kg.h, and -0.10 +/- 0.08 vs. -0.08 +/- 0.05 micro mol/kg.h, respectively). These results indicated that whole-body tissue responsiveness to the net anabolic effect of GH is similar in OB and NW women. Hence, we inferred that hyposomatotropism may promote amino acid oxidation and blunt protein turnover in abdominal obesity. However, hyposomatotropism cannot account for all anomalous features of protein metabolism in abdominally obese humans.
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PMID:Growth hormone blunts protein oxidation and promotes protein turnover to a similar extent in abdominally obese and normal-weight women. 1246 70

Excessive consumption of energy and fat increases the risk for obesity. Snacks containing sucrose polyesters (SPE) as a dietary fat replacer are on the market in the United States. SPE products have been shown to lower concentrations of serum carotenoids in short-term studies. Experimental studies on the longer-term effects on health of decreased carotenoid concentrations are lacking. A 1-y randomized, double-blind, placebo-controlled parallel trial was performed. Subjects (n = 380) with a habitual low or high fruit and vegetable intake were assigned to the treatments (0, 7, 10 or 17 g/d SPE). SPE was given in the form of spreads, chips or both. The groups were compared for serum carotenoids, vitamins and markers of oxidative damage, eye health, cardiovascular health and immune status. After 1 y, serum lipid-adjusted carotenoids showed the largest decrease in the SPE chips and spread group (17 g/d) compared with the control group [alpha-carotene 33%; beta-carotene 31%, lycopene 24%, beta-cryptoxanthin 18%, lutein 18% (all P < 0.001) and zeaxanthin 13% (P < 0.05)]. Consumption of SPE spread (10 g/d SPE) decreased carotenoid concentrations by 11-29% (all P < 0.05). SPE chips (7 g/d SPE) decreased zeaxanthin (11%), beta-carotene (12%) and alpha-carotene (21%; all P < 0.05). Serum lipid adjusted alpha-tocopherol decreased significantly by 6-8% (all P < 0.001) in all SPE groups. No negative effects were observed on markers of oxidation, eye health, cardiovascular health or immune status. This study shows that decreases in serum carotenoid concentrations do not affect possible markers of disease risk.
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PMID:Decreased carotenoid concentrations due to dietary sucrose polyesters do not affect possible markers of disease risk in humans. 1261 43

Protein tyrosine phosphatase 1B (PTP1B) plays a key role as a negative regulator of insulin and leptin signalling and is therefore considered to be an important molecular target for the treatment of type 2 diabetes and obesity. Detailed structural information about the structure of PTP1B, including the conformation and flexibility of active-site residues as well as the water-molecule network, is a key issue in understanding ligand binding and enzyme kinetics and in structure-based drug design. A 1.95 A apo PTP1B structure has been obtained, showing four highly coordinated water molecules in the active-site pocket of the enzyme; hence, the active site is highly solvated in the apo state. Three of the water molecules are located at positions that approximately correspond to the positions of the phosphate O atoms of the natural substrate phosphotyrosine and form a similar network of hydrogen bonds. The active-site WPD-loop was found to be in the closed conformation, in contrast to previous observations of wild-type PTPs in the apo state, in which the WPD-loop is open. The closed conformation is stabilized by a network of hydrogen bonds. These results provide new insights into and understanding of the active site of PTP1B and form a novel basis for structure-based inhibitor design.
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PMID:Water-molecule network and active-site flexibility of apo protein tyrosine phosphatase 1B. 1533 22

This study surveyed all cardiologists in a large coalition of cardiology groups. A 1-page, 25-item anonymous questionnaire containing 3 sections (demographics, medical history, and current medications and supplements) was used. Data from returned questionnaires were analyzed and compared with those in national databases. Eight hundred surveys were sent, and complete data were available for analysis on 471 (59%). The average age of the participants was 48.6 years; 7.1% were women. The average body mass index (BMI) was 25 kg/m(2), and 8% were obese (BMI > or =30 kg/m(2)); 1.3% were active smokers; 89% exercised > or =1 time/week; and 72% had > or =1 alcoholic drink/week. Red wine was the most frequently consumed alcoholic beverage. Associated cardiovascular risks included dyslipidemia (28%), hypertension (14%), and diabetes mellitus (0.6%). Four percent had experienced coronary events. Compared with matched cohorts from the United States (US) population, cardiologists reported lower rates of hypertension, dyslipidemia, and diabetes mellitus, and the rates of smoking and obesity were 1/18 and 1/3 those of the US population, respectively. Aspirin and statins were each taken daily by about 1/3 of the participants. A cardiologist with dyslipidemia was 5 times as likely to be treated and a cardiologist with hypertension was almost twice as likely to be treated as an American adult man with either of these disorders, respectively. In conclusion, cardiologists appear to follow healthier lifestyles than the general adult US population.
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PMID:Personal health habits of American cardiologists. 1656 24

Pseudohypoparathyroidism is a parathyroid hormone resistance condition, characterised by biochemical findings of hypocalcaemia or normocalcaemia with inappropriately elevated parathyroid hormone level and usually with a typical osteodystrophy feature. We report an infant with pseudohypoparathyroidism type Ia, who presented with obesity and calcinosis cutis as a clue to diagnosis. A 1-year-old female infant presented with suspected Cushing syndrome. She had round face, flushed cheeks, short nose and low nasal bridge. The infant was normotensive and not virilised. Investigations for Cushing syndrome were all negative. Calcinosis cutis was detected over both legs and the abdominal wall. Parathyroid hormone level was inappropriately elevated with a slightly high calcium level. Her mother was also noted to have Albright's hereditary osteodystrophy features with normal calcium and parathyroid hormone levels. Therefore, the diagnoses of infantile pseudohypoparathyroidism type Ia and maternal pseudopseudohypoparathyroidism were made. This infant presented with an early manifestation of Albright's hereditary osteodystrophy. Diagnosis of pseudohypoparathyroidism should be considered as an unusual cause of obesity in infants, particularly in the differential diagnosis of Cushing syndrome when tall stature rather than growth failure is present.
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PMID:Early manifestation of obesity and calcinosis cutis in infantile pseudohypoparathyroidism. 1709 21


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