UMLS:C0028754 - FACTA Search

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

We have evaluated the effectiveness of a very low caloric content diet (VLCD) during 6 weeks in patients with severe obesity (grades II and III). Twenty-seven men and 61 women were selected for evaluation of anthropometric (weight, body mass index [BMI], waist, hip, C/c, fatty weight and intra-abdominal fatty area) and biochemical (creatinine-height index [CHI], albumin, transferrin, retinol binding protein [RBP], prealbumin, C3, and lymphocytes count) malnutrition parameters, at the beginning and after 6 weeks of treatment with VLCD. In men we found a significant decrease of weight, BMI, waist, hip, fatty weight, and intra-abdominal fatty area. In women the decrease of weight, BMI, hip, and fatty weight was also significant. We found baseline malnutrition in 7.4% of men and in 14.7% of women, and after the treatment in 22.2% of men and in 34.4% of women (p < 0.05). With regard to the biochemical parameters of protein malnutrition, only men showed significant decrease in the CHI and only women showed significant decrease in transferrin, RBP, prealbumin, and C3. In conclusion, we can state that different types of VLCD are effective for weight loss in severe obese subjects. However, within a period of follow-up of 6 weeks we have detected the presence of protein malnutrition, especially in women, being in these patients affected the visceral compartment while in men the muscular compartment is affected.
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PMID:[Malnutrition evaluation in obese patients of both sexes on a very low caloric content diet]. 1527 64

Oxidation of ethanol via alcohol dehydrogenase (ADH) explains various metabolic effects of ethanol but does not account for the tolerance. This fact, as well as the discovery of the proliferation of the smooth endoplasmic reticulum (SER) after chronic alcohol consumption, suggested the existence of an additional pathway which was then described by Lieber and DeCarli, namely the microsomal ethanol oxidizing system (MEOS), involving cytochrome P450. The existence of this system was initially challenged but the effect of ethanol on liver microsomes was confirmed by Remmer and his group. After chronic ethanol consumption, the activity of the MEOS increases, with an associated rise in cytochrome P450, especially CYP2E1, most conclusively shown in alcohol dehydrogenase negative deer mice. There is also cross-induction of the metabolism of other drugs, resulting in drug tolerance. Furthermore, the conversion of hepatotoxic agents to toxic metabolites increases, which explains the enhanced susceptibility of alcoholics to the adverse effects of various xenobiotics, including industrial solvents. CYP2E1 also activates some commonly used drugs (such as acetaminophen) to their toxic metabolites, and promotes carcinogenesis. In addition, catabolism of retinol is accelerated resulting in its depletion. Contrasting with the stimulating effects of chronic consumption, acute ethanol intake inhibits the metabolism of other drugs. Moreover, metabolism by CYP2E1 results in a significant release of free radicals which, in turn, diminishes reduced glutathione (GSH) and other defense systems against oxidative stress which plays a major pathogenic role in alcoholic liver disease. CYP1A2 and CYP3A4, two other perivenular P450s, also sustain the metabolism of ethanol, thereby contributing to MEOS activity and possibly liver injury. CYP2E1 has also a physiologic role which comprises gluconeogenesis from ketones, oxidation of fatty acids, and detoxification of xenobiotics other than ethanol. Excess of these physiological substrates (such as seen in obesity and diabetes) also leads to CYP2E1 induction and nonalcoholic fatty liver disease (NAFLD), which includes nonalcoholic fatty liver and nonalcoholic steatohepatitis (NASH), with pathological lesions similar to those observed in alcoholic steatohepatitis. Increases of CYP2E1 and its mRNA prevail in the perivenular zone, the area of maximal liver damage. CYP2E1 up-regulation was also demonstrated in obese patients as well as in rat models of obesity and NASH. Furthermore, NASH is increasingly recognized as a precursor to more severe liver disease, sometimes evolving into "cryptogenic" cirrhosis. The prevalence of NAFLD averages 20% and that of NASH 2% to 3% in the general population, making these conditions the most common liver diseases in the United States. Considering the pathogenic role that up-regulation of CYP2E1 also plays in alcoholic liver disease (vide supra), it is apparent that a major therapeutic challenge is now to find a way to control this toxic process. CYP2E1 inhibitors oppose alcohol-induced liver damage, but heretofore available compounds are too toxic for clinical use. Recently, however, polyenylphosphatidylcholine (PPC), an innocuous mixture of polyunsaturated phosphatidylcholines extracted from soybeans (and its active component dilinoleoylphosphatidylcholine), were discovered to decrease CYP2E1 activity. PPC also opposes hepatic oxidative stress and fibrosis. It is now being tested clinically.
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PMID:The discovery of the microsomal ethanol oxidizing system and its physiologic and pathologic role. 1555 33

Under- and over-nutrition in children in KwaZulu-Natal, South Africa was investigated comparing data collected from primary school children in a rural district (643 children aged 8-11 years in 1994) with secondary data from the National Schools Study (16,179 children, 4-11 years in 1994), the Vitamin A Consultative Group Study (408 children, 2-5 years in 1994) and the Income Dynamics Study (1,593 children, 2-11 years in 1998). Stunting and wasting (WHO/NCHS guidelines) and overweight and obesity (International Obesity Task Force guidelines) were retrospectively analysed from these studies and compared in the children aged 4-5 and 8-11 years. There was moderate stunting in 10-25%, wasting in 1-6%, 5-24% were overweight and 1-10% obese. Girls in the National Schools Study (p<0.005) and in the primary datasets (p=0.02) had a significantly higher prevalence of overweight than boys; girls (1.4%) were also more obese than boys (0.9%) in the Schools Study (p=0.002), and the boys significantly more stunted (p<0.005) and wasted (p<0.005). An increasing prevalence of overweight and obesity was seen in both the 4-5- and 8-11-year age-groups. The finding that moderate stunting co-exists with overweight and obesity suggests that patterns of under- and over-nutrition in South African children are changing and might indicate the early stages of a complex nutritional transition. Action is required to prevent the future risk of non-communicable diseases.
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PMID:Changing patterns of under- and over-nutrition in South African children-future risks of non-communicable diseases. 1581 43

Adipose tissue is an important retinoid depot and retinoids are known to influence white and brown adipocyte metabolism. Identifying nutrients that can affect the biological activity of the adipose organ would be of great medical interest in the light of the current obesity epidemic and related disorders in developed countries. The vast majority of mammal studies of chronic administration of oral beta-carotene have used murine models, while few have employed mammals exhibiting uptake and processing of intestinal beta-carotene similar to those of humans. While rodents transform practically all ingested beta-carotene into retinol, in ferrets, as in humans, part of the beta-carotene is absorbed and released into the circulation intact. We studied the effects of 6-month daily administration of two doses of oral beta-carotene (0.8 or 3.2 mg/kg/day) on ferret body weight, size of body fat depots, and, using morphological and morphometric methods, on subcutaneous (inguinal) white adipose tissue (WAT). Because of the oral mode of administration, liver, stomach, and small and large intestine were also studied. Control animals received the vehicle. Data show that at the end of treatment the higher dose induced significantly higher body weight compared with controls and significantly higher inguinal fat depot compared with animals treated with the lower dose. In addition, chronic treatment with beta-carotene induced a dose-dependent hypertrophy of white adipocytes and increased neoangiogenesis in subcutaneous WAT in all treated ferrets. Vasculogenesis was independent of adipocyte hypertrophy. We also found focally evident liver steatosis in the ferrets treated with the higher dose of beta-carotene. The other gastrointestinal tract organs studied were not significantly different from those of control animals.
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PMID:Morphology of ferret subcutaneous adipose tissue after 6-month daily supplementation with oral beta-carotene. 1589 57

In obesity and type 2 diabetes, expression of the GLUT4 glucose transporter is decreased selectively in adipocytes. Adipose-specific Glut4 (also known as Slc2a4) knockout (adipose-Glut4(-/-)) mice show insulin resistance secondarily in muscle and liver. Here we show, using DNA arrays, that expression of retinol binding protein-4 (RBP4) is elevated in adipose tissue of adipose-Glut4(-/-) mice. We show that serum RBP4 levels are elevated in insulin-resistant mice and humans with obesity and type 2 diabetes. RBP4 levels are normalized by rosiglitazone, an insulin-sensitizing drug. Transgenic overexpression of human RBP4 or injection of recombinant RBP4 in normal mice causes insulin resistance. Conversely, genetic deletion of Rbp4 enhances insulin sensitivity. Fenretinide, a synthetic retinoid that increases urinary excretion of RBP4, normalizes serum RBP4 levels and improves insulin resistance and glucose intolerance in mice with obesity induced by a high-fat diet. Increasing serum RBP4 induces hepatic expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) and impairs insulin signalling in muscle. Thus, RBP4 is an adipocyte-derived 'signal' that may contribute to the pathogenesis of type 2 diabetes. Lowering RBP4 could be a new strategy for treating type 2 diabetes.
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PMID:Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. 1603 6

The aim of this study was to determine whether there is an association between the nutritional status of the mother and that of her 2-year-old to 5-year-old child in a rural village in South Africa where there is a high prevalence of childhood malnutrition (in particular, deficiencies of vitamin A and iron) and of maternal obesity. A blood sample and anthropometric measurements were obtained for 118 child-mother pairs. There was a positive mother-child correlation for serum ferritin (R=0.2304, P<0.05) and haemoglobin (R=0.2664, P<0.01) concentrations, respectively. The child of an anaemic mother had a relative risk of 1.632 of also being anaemic. There was no mother-child association for either serum retinol concentration or anthropometric measurements. Serum retinol concentrations showed a positive correlation with both serum ferritin (mothers only; R=0.2161, P<0.01) and haemoglobin (R=0.2807, P<0.01 for mothers; and R=0.2710, P < 0.01 for children) concentrations. The mother-child association for iron status is probably because of an inadequate dietary intake and low bioavailability of dietary iron, which are major causes of iron deficiency. The lack of mother-child association for serum retinol concentration could probably be ascribed to the fact that children are more susceptible to vitamin A deficiency than adults because of childhood diseases.
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PMID:Is there an association between the nutritional status of the mother and that of her 2-year-old to 5-year-old child? 1609 35

Vitamin A (retinoid) is required in the adult brain to enable cognition, learning, and memory. While brain levels of retinoid diminish over the course of normal ageing, retinoid deficit is greater in late onset Alzheimer disease (LOAD) brains than in normal-aged controls. This paper reviews recent evidence supporting these statements and further suggests that genes necessary for the synthesis, transport and function of retinoid to and within the ageing brain are appropriate targets for treatment of LOAD. These genes tend to be clustered with genes that have been proposed as candidates in LOAD, are found at chromosomal regions linked to LOAD, and suggest the possibility of an overall coordinated regulation. This phenomenon is termed Chromeron and is analogous to the operon mechanism observed in prokaryotes. Suggested treatment targets are the retinoic-acid inactivating enzymes (CYP26)s, the retinol binding and transport proteins, retinol-binding protein (RBP)4 and transthyretin (TTR), and the retinoid receptors. TTR as a LOAD target is the subject of active investigation. The retinoid receptors and the retinoid-inactivating enzymes have previously been proposed as targets. This is the first report to suggest that RBP4 is an amenable treatment target in LOAD. RBP4 is elevated in type-2 diabetes and obesity, conditions associated with increased risk for LOAD. Fenretinide, a novel synthetic retinoic acid (RA) analog lowers RBP4 in glucose intolerant obese mice. The feasibility of using fenretinide either as an adjunct to present LOAD therapies, or on its own as an early prevention strategy should be determined.
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PMID:Retinoid receptors, transporters, and metabolizers as therapeutic targets in late onset Alzheimer disease. 1700 93

Insulin resistance constitutes a pathophysiologic link between obesity, atherosclerosis, and/or cardiovascular complications. Retinol binding protein 4 (RBP4) is a newly discovered adipocyte product that modulates glucose metabolism and consequently induces insulin resistance. We investigated the association between serum RBP4 levels and insulin resistance in obese and nonobese adolescents. A total of 87 nonobese (60 males and 27 females) and 85 obese (62 males and 23 females) apparently healthy adolescents, 12 to 18 years old, were included in this study. A questionnaire was used to obtain participant medical history and lifestyle information, such as smoking and alcohol ingestion habits. Subjects' anthropometric measurements were taken to calculate for body mass index and waist-to-hip ratio. Serum RBP4 levels were measured by an enzyme immunoassay kit. High-sensitivity C-reactive protein, fasting glucose, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and fasting insulin were measured. Low-density lipoprotein cholesterol level and homeostatic model assessment of insulin resistance (HOMA-IR) were calculated. Males had significantly higher RBP4 levels than females. Serum RBP4 levels were significantly higher in the obese group compared with the nonobese group. In all subjects, RBP4 was positively correlated with adiposity index (body mass index, waist circumference, waist-to-hip ratio), systolic and diastolic blood pressures, glucose tolerance index (fasting glucose, insulin, HOMA-IR), lipid profile (total cholesterol, triglycerides), and inflammatory indices (high-sensitivity C-reactive protein, white blood cell count). In multiple linear regression analysis, RBP4 was independently associated with age, HOMA-IR, and triglyceride levels in the nonobese group and with sex and triglyceride levels in the obese group. These results suggest that serum RBP4 might have clinical implications for lipid metabolism and insulin action in adolescents.
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PMID:Association of serum retinol binding protein 4 and insulin resistance in apparently healthy adolescents. 1729 20

DNA microarrays have provided medical researchers with a powerful tool to study the mechanisms of complex diseases, including obesity and type 2 diabetes (T2D). The technology has been used to dissect virtually every aspect of the genetic and molecular basis of these two diseases. Gene expression profiling is the major application of DNA microarrays so far. Subcutaneous fat, visceral fat, adipocyte and preadipocyte, muscle, liver, pancreas and specific nuclei in the hypothalamus under normal and disease conditions are used in addressing the profile of gene expression in obesity and T2D. Comparisons of fat depots in humans and animal models - including ob/ob and db/db mice, diet-induced obese mice, fa/fa Zucker rats, gene knockout (plin (-/-), GLUT4 (-/-)) and transgenic mice (GLUT4-Tg) - have been employed in microarray experiments. The effects of various interventions, such as hormonal and drug treatments, exercise, and surgery, have been studied to determine the expression profile of different developmental stages in cells and the effect of treatment on the two diseases. In this review, the application of microarrays in elucidating the role of retinol binding protein 4 as a link between obesity and T2D is discussed. The possible role in obesity of a common genetic variant near the INSIG2 gene and the discovery of the BBS9 gene are also discussed. The problems and challenges are summarized under eight categories and suggestions for the future direction of research in this area are proposed.
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PMID:Application of DNA microarrays in the study of human obesity and type 2 diabetes. 1741 94

The metabolism of vitamin A and the diverse effects of its metabolites are tightly controlled by distinct retinoid-generating enzymes, retinoid-binding proteins and retinoid-activated nuclear receptors. Retinoic acid regulates differentiation and metabolism by activating the retinoic acid receptor and retinoid X receptor (RXR), indirectly influencing RXR heterodimeric partners. Retinoic acid is formed solely from retinaldehyde (Rald), which in turn is derived from vitamin A. Rald currently has no defined biologic role outside the eye. Here we show that Rald is present in rodent fat, binds retinol-binding proteins (CRBP1, RBP4), inhibits adipogenesis and suppresses peroxisome proliferator-activated receptor-gamma and RXR responses. In vivo, mice lacking the Rald-catabolizing enzyme retinaldehyde dehydrogenase 1 (Raldh1) resisted diet-induced obesity and insulin resistance and showed increased energy dissipation. In ob/ob mice, administrating Rald or a Raldh inhibitor reduced fat and increased insulin sensitivity. These results identify Rald as a distinct transcriptional regulator of the metabolic responses to a high-fat diet.
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PMID:Retinaldehyde represses adipogenesis and diet-induced obesity. 1755 31

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