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

Most progestogens in oral contraceptives are testosterone derivatives and have androgenic side effects such as weight increase, acne and hirsutism. They pose a problem to many women just like the clinical picture of the polycystic ovary syndrome (PCO) with obesity, hirsutism, acne and amenorrhea. The aim of this study was to evaluate androgenicity of the most used progestogens with special reference to desogestrel which is a new progestogen. Radioimmunoassay was used for hormone determination while serum proteins were determined with electroimmunoassay or in some studies for sex hormone binding globulin (SHBG) with capacity assays. Serum lipids and lipoproteins were determined in serum and after ultracentrifugation in HDL, LDL and VLDL fractions. In a comparative study on levonorgestrel/ethinylestradiol (EE) (n = 10) versus desogestrel/ethinylestradiol (n = 10) the latter combination gave increases in SHBG capacity while the former did not. Similar increases in estrogen-sensitive proteins cortisol binding globulin (CBG) and ceruloplasmin indicated that the estrogenicity and "antiestrogenicity" was the same for the two combinations whereas the androgenicity of levonorgestrel was greater giving a reduction in the EE-induced increase in SHBG (SHBG is increased by estrogens and suppressed by androgens). When giving desogestrel 0.125-0.500 mg and lynestrenol 5 mg alone in daily doses to a group of regularly menstruating women (n = 8) strong suppression of SHBG was achieved while ceruloplasmin, CBG and thyroxine binding globulin (TBG) did not change. TBG is decreased and prealbumin increased by androgenic/anabolic activity but only a moderate increase in prealbumin was found during lynestrenol treatment. The changes in SHBG are probably the result of a dose-dependent receptor interaction related to 17 alpha-alkylation in 19-norsteroids. Twenty women with PCO were treated for 8 months with 0.150 mg desogestrel/0.030 mg EE. Evaluation was done before treatment and after 3 and 8 "pill" cycles regarding androgens, estradiol, SHBG, hirsutism and body weight. Spontaneous menstrual cycles were assessed after treatment. Serum lipids and lipoproteins were studied before treatment and at the end of the third "cycle". In PCO the suppression of increased total and free testosterone levels (in comparison to 22 healthy women) was evident during treatment, concordant with increases in SHBG capacity. Hirsutism was suppressed and body weight was reduced in obese women.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Pharmacodynamic studies on desogestrel administered alone and in combination with ethinylestradiol. 316 Dec 65

Effects of obesity and age on copper, iron, zinc, sodium, potassium, and protein were compared in liver, kidney, brain, and muscle of obese (fa/fa) and nonobese (non-fa/fa) male Zucker rats. Blood plasma cerulopasmin, copper, zinc, sodium, and potassium were also determined. Mean brain weight of fa/fa rats was less than that of non-fa/fa rats at 12 weeks of age; mean brain protein concentration was greater in fa/fa than in non-fa/fa at 5 and 12 weeks of age. At 18-19 days of age, mean sodium concentration (mg/g protein) in liver of fa/fa was less than that of non-fa/fa. At 5 weeks of age, mean copper concentration (microgram/g protein) in kidney was greater in fa/fa. Mean total copper, iron, zinc, sodium, and potassium in liver and kidney were greater in fa/fa than in non-fa/fa at 5 weeks because of the larger livers and kidneys of fa/fa. Mean concentrations of copper, zinc, sodium, and potassium per gram of brain protein were slightly (6-10%) less in fa/fa than in non-fa/fa at 5 weeks. By 12 weeks, mean concentrations of copper in liver, kidney, (tibialis) muscle, and blood plasma, ceruloplasmin in blood plasma, zinc in liver and muscle, iron in muscle, and sodium in liver were greater in fa/fa than in non-fa/fa. However, total amount of each mineral in muscle at 12 weeks was less in fa/fa than in non-fa/fa because of the smaller mean muscle weight of fa/fa. Mean concentrations of copper and zinc in brain and of iron in liver and brain were less in fa/fa than in non-fa/fa at 12 weeks. The major age-related changes in fa/fa that were not observed in non-fa/fa were large increases in liver and kidney copper between 5 and 12 weeks of age. It seems that the abnormal mineral metabolism is a consequence of the obesity, but the mechanisms are not identified.
 ...
PMID:Developmental changes of selected minerals in Zucker rats. 319 37

Experiments were conducted to determine if food intake and adrenalectomy influenced abnormal antioxidant defense mechanisms observed in obese mice. Paired male C57BL/6J mice of two genotypes, obese (ob/ob) and lean (+/?), were fed a nonpurified diet ad libitum or restricted (2.5 g/d) until 3 mo old. Obese mice had larger livers and kidneys but smaller brains than lean mice. Plasma ceruloplasmin activity of obese mice was 240% of that of lean mice. Restricting food intake but not adrenalectomy reduced this difference, but ceruloplasmin activity of obese mice was still 150% of that of restricted-fed lean mice. Glutathione peroxidase (GSH-Px) activity in liver of obese mice was 70% of that in control lean mice; however, in kidney GSH-Px activity was 135% of that in obese mice. Both liver and kidney GSH-Px differences were eliminated by food restriction but not by adrenalectomy. Blood and brain GSH-Px activity was not influenced by the mutation. Liver and kidney copper-zinc superoxide dismutase activity was lower in obese mice than in lean littermates, 30 and 20%, respectively. Food restriction eliminated this difference in liver but not in kidney. Glutathione S-transferase activity using 1-chloro-2,4-dinitrobenzene as substrate was 55% lower in liver (not kidney) of obese mice than in lean mice and this difference was not markedly influenced by food restriction. Obese mice have marked changes in the steady-state activities of a number of protective enzymes that are organ dependent and, in part, due to the hyperphagia associated with this mutation.
 ...
PMID:Influence of genetic obesity, food intake and adrenalectomy in mice on selected trace element-dependent protective enzymes. 337 40

The concentrations (micrograms/gram dry wt) of four essential trace metals in various tissues from C57BL/6J lean (+/?) and obese (ob/ob) mice were determined. Lower concentrations of zinc were found in liver, femur, small intestine and muscle from obese mice than in those from lean mice at 22 wk of age. The concentrations of copper in liver, femur, small intestine, muscle and testes, iron in liver, femur, muscle and plasma, and manganese in liver, femur and small intestine from adult obese mice were also significantly below the concentrations present in tissues from age-matched lean mice. Hepatic concentrations of zinc, copper and manganese in obese mice were also lower than those in lean mice when the different amounts of neutral lipid in obese and lean liver were considered. In contrast with the trend towards lower concentrations of trace metals in tissues from adult obese mice, plasma zinc and copper levels and ceruloplasmin activity were higher in adult obese mice than in lean controls. The effect of genetic obesity on tissue trace metals concentrations was similar in male and female mice. Several tissues from young (5-6 wk of age) obese mice also had lower concentrations of the trace metals than age-matched lean mice, although the differences were not as great as in adults. These data demonstrate that chronic obesity in the genetically obese (ob/ob) mouse is associated with lower concentrations, but not necessarily lower total quantities, of several inorganic micronutrients in tissues. The possibility tht chronic obesity alters the nutritional requirements for these trace metals is discussed.
 ...
PMID:Influence of genetic obesity on tissue concentrations of zinc, copper, manganese and iron in mice. 376 Oct

The serum viscosity of diabetic patients has been found to be increased. The elevation averaged 8% above healthy subjects and 6% above nondiabetic patients. The serum viscosity elevation was greater when diabetic sequelae associated with microangiopathy were present. No relation of serum viscosity to age, sex, obesity, duration of disease, or type of treatment was demonstrated. Serum total protein and glucose levels were found to be correlated with serum viscosity, and increases in their serum concentrations were observed in diabetes. Analysis demonstrated that their elevation did not explain either the viscosity increase or the difference in viscosity between diabetics with and without sequelae.Intrinsic viscosity, abbreviated [eta], is a concentration-independent solute property related to molecular shape. [eta] was found to be 7% higher in diabetic than in normal serum. The [eta] difference accounted for at least half of the serum viscosity elevation. The rest of the increase was due to increased serum protein level and increased nonprotein solids, presumably glucose and lipid. Associated with increased [eta] was a decline in albumin: globulin ratio and elevation of the acute phase reactant proteins, alpha(1)-acid glycoprotein, alpha(1)-antitrypsin, haptoglobin, and ceruloplasmin. Studies comparing diabetic and normal serum fractionated by using 21.5% sodium sulfate showed that changes in [eta] were attributable to changes in serum protein composition rather than an inherent qualitative disturbance of protein present in one of the fractions. Since serum viscosity is elevated in early diabetes, it may be a part of the metabolic disturbance of diabetes and could play a role in the development of diabetic microangiopathy.
 ...
PMID:Disturbance of serum viscosity in diabetes mellitus. 420 23

Abnormalities of copper distribution in tissues and serum has been described in obese subjects. In this prospective study, we evaluated the seric level of copper by atomic absorption in a group of 32 obese (BMI > or = 30 kg/m2) compared to a group of 32 healthy subjects. We have noted an elevation of serum copper in obese with a middle level of 133 mg/dl significantly superior to the middle level of serum copper of healthy subjects, 108 mg/dl (p < 0.001). In another hand, we have noticed that the levels of serum cooper rise with the BMI. In fact, 58.3% of the obese that have a BMI > or = 40 kg/m2 show a high concentration of serum copper although only 5% of obese with BMI < 40 kg/m2 show this high concentration. This work must be completed by the determination of ceruloplasmin levels in a larger group of obese in order to establish correlations between the serum ceruloplasmin levels, the serum copper levels and the obesity.
 ...
PMID:[Serum copper levels in obesity: a study of 32 cases]. 1177 33

The presence of steatosis and inflammatory infiltrate in liver biopsies is essential for the diagnosis of non-alcoholic steatohepatitis (NASH). These findings are similar to those with alcoholic liver disease. However, in the NASH-situation alcohol doesn't play an important role. Risk factors for the development of NASH are obesity and diabetes. Most of the patients are clinically asymptomatic. This means, that a diagnosis of NASH is a diagnosis of exclusion: Viral induced, autoimmune, metabolic and toxic liver disease have to be excluded. The disease has a benign clinical course. The risk of cirrhosis is low. So far, there is no established treatment. Preliminary reports suggest a positive effect of weight-loss and ursodeoxycholic acid. Wilson's disease, a copper storage disorder, in which biliary copper excretion is reduced, is inherited as an autosomal recessive trait. Most patients with Wilson disease become symptomatic between the ages of 6 and 15. In about 90% of patients serum ceruloplasmin levels and serum copper concentrations are reduced. Copper excreation is increased. Histologic examination of liver biopsy specimens reveals fatty infiltration, Mallory bodies and ballooned glycogen nuclei, abnormalities which are also found in alcoholic liver disease. The definitive diagnostic parameter is the quantitative determination of liver copper content (> 250 micrograms/g dryweight). Untreated Wilson disease is always fatal. Lifelong treatment with anti-copper drugs are essential, D-penicillamine being the firstline therapy. Hereditary hemochromatosis (HH) is an iron overload disease inherited as an autosomal recessive trait. The frequency of the disease is high. The first symptoms usually can be found at the age of 20-50 years. Arthralgia develops in up to 50% of the patients. Many organs are involved, most often the liver. The organ is usually enlarged, transaminases are always moderately elevated. Laboratory findings disclose a marked elevation in serum ferritin and transferrin saturation. More than 80% of HH-patients are homozygous for the C282Y-mutation in the HFE-gene. The firstline treatment of HH is phlebotomy. Treatment is lifelong. When serum ferritin drops below 50 micrograms/l, the frequency of phlebotomy should be reduced (4-12 per year). If the patient already has cirrhosis, the risk of HCC is very high.
 ...
PMID:[Rare, but important chronic liver diseases]. 1250 71

Cross-sectional studies have associated obesity and other components of the so-called metabolic syndrome with low-grade inflammation. The temporal and causal relations of this association have not been fully explored. This study explored whether elevated levels of inflammation-sensitive plasma proteins (ISPs) (fibrinogen, orosomucoid, alpha1-antitrypsin, haptoglobin, and ceruloplasmin) are associated with future weight gain. Five ISPs were measured in 2,821 nondiabetic healthy men (38-50 years of age) who were reexamined after a mean follow-up of 6.1 years. Future weight gain was studied in relation to the number of elevated ISPs (i.e., in the top quartile). The proportion with a large weight gain (75th percentile >/= 3.8 kg) was 21.0, 25.9, 26.8, and 28.3%, respectively, among men with none, one, two, and three or more ISPs in the top quartile (P for trend 0.0005). This relation remained significant after adjustments for weight at baseline, follow-up time, height (at baseline and follow-up), physical inactivity (at baseline and follow-up), smoking (at baseline and follow-up), high alcohol consumption, and insulin resistance. The relations were largely similar for all individual ISPs. Elevated ISP levels predict a large weight gain in middle-aged men. This relation could contribute to the relation between inflammation, the metabolic syndrome, and cardiovascular disease.
 ...
PMID:Inflammation-sensitive plasma proteins are associated with future weight gain. 1288 28

Oxidative stress and inflammation are involved in the initiation and progression of obesity and diabetes mellitus. The aim of our study was to find out some markers of oxidative stress in twenty obese patients with type 2 diabetes mellitus (group D) and twenty age-matched obese subjects (group O) and compare the results with the control values from twenty matched healthiy subjects (group H). Spectrophotometric methods were used. For the following plasma parameters: ceruloplasmin, d-ROM (determinable Reactive Oxygen Metabolites), alpha-dicarbonyls, the values were modified in the same way for the groups of patients versus healthy subjects. The patients had higher alpha-dicarbonyls levels than the controls (for D versus H, p<0.047 and for O versus H, p<0.043). There were not significant differences for plasma ceruloplasmin and d-ROM levels. Comparing group O versus D, all the above parameters had very close values. The antioxidant capacity (AC) was higher in group O versus group H (p<0.001) and higher in group O versus D (p<0.02). The high AC for obese patients may be due to hyperuricemia. A negative correlation between AC and d-ROM concentrations and a positive correlation between ceruloplasmin and AC levels was observed for group D. Our data underline that in type 2 diabetes mellitus and obesity, the plasma markers of oxidative stress are modified in the same way. Oxidative stress may be a "connector" between these two diseases. Probably body fat reduction (for obese individuals) diminishes oxidant formation and, in its turn, the incidence of obesity related diseases, such as diabetes mellitus.
 ...
PMID:A comparative oxidative stress study--obesity with and without diabetes mellitus. 1681 85

There are several cofactors which affect body iron metabolism and accelerate iron overload. Alcohol and hepatic viral infections are the most typical examples for clarifying the role of cofactors in iron overload. In these conditions, iron is deposited in hepatocytes and Kupffer cells and reactive oxygen species (ROS) produced through Fenton reaction have key role to facilitate cellular uptake of transferrin-bound iron. Furthermore, hepcidin, antimicrobial peptide produced mainly in the liver is also responsible for intestinal iron absorption and reticuloendothelial iron release. In patients with ceruloplasmin deficiency, anemia and secondary iron overload in liver and neurodegeneration are reported. Furthermore, there is accumulating evidence that fatty acid accumulation without alcohol and obesity itself modifies iron overload states. Ineffective erythropoiesis is also an important factor to accelerate iron overload, which is associated with diseases such as thalassemia and myelodysplastic syndrome. When this condition persists, the dietary iron absorption is increased due to the increment of bone marrow erythropoiesis and tissue iron overload will thereafter occurs. In porphyria cutanea tarda, iron is secondarily accumulated in the liver.
 ...
PMID:Iron overload and cofactors with special reference to alcohol, hepatitis C virus infection and steatosis/insulin resistance. 1772 91


1 2 3 Next >>