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

Enterocytes assemble dietary lipids into chylomicron particles that are taken up by intestinal lacteal vessels and peripheral tissues. Although chylomicrons are known to assemble in part within membrane secretory pathways, the modifications required for efficient vascular uptake are unknown. Here we report that the transcription factor pleomorphic adenoma gene-like 2 (PlagL2) is essential for this aspect of dietary lipid metabolism. PlagL2(-/-) mice die from postnatal wasting owing to failure of fat absorption. Lipids modified in the absence of PlagL2 exit from enterocytes but fail to enter interstitial lacteal vessels. Dysregulation of enterocyte genes closely linked to intracellular membrane transport identified candidate regulators of critical steps in chylomicron assembly. PlagL2 thus regulates important aspects of dietary lipid absorption, and the PlagL2(-/-) animal model has implications for the amelioration of obesity and the metabolic syndrome.
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PMID:Loss of the PlagL2 transcription factor affects lacteal uptake of chylomicrons. 1798 86

The term "reverse epidemiology" is used to indicate that such surrogates of cardiovascular risk and metabolic syndrome as obesity, hypercholesterolemia and hypertension are paradoxically associated with greater survival in individuals with chronic disease states and wasting, including dialysis patients, in whom the short-term survival is the issue at hand. It is being debated whether the crossing curves of the obesity-mortality association in dialysis patients vs. the general population reflect the residual confounding that needs to be controlled away statistically, or whether they have biological plausibility in sharp contradistinction to the currently dominating Framingham paradigm. In the rush to define the crossing curves as statistical artifact and to dismiss the term "reverse epidemiology" as a misnomer, we may miss the opportunity to gain information housed in those crossing lines and may miss the bigger picture, i.e., how to improve longevity in dialysis patients. Even though some of the survival paradoxes in dialysis patients appear to fulfill the Hill's criteria of causation, there are still two major drawbacks: (1) convincing pathophysiologic pathways to link dialysis patient survival to obesity, fat accumulation, higher serum lipoprotein levels or slightly higher than normal blood pressure values are yet to be verified in animal and other scientifically sound models; and (2) randomized controlled trials need to show that nutritional interventions resulting in weight gain can lead to greater survival in dialysis patients. Studying the survival paradoxes may lead to a paradigm shift by establishing targets beyond the Framingham guidelines for populations with chronic disease states.
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PMID:What is so bad about reverse epidemiology anyway? 1799 Dec 10

We analyzed the nutritional status of urban and rural schoolchildren from Mendoza (Argentina), but avoided rural and urban categorization by generating subpopulations as a function of their socioenvironmental characteristics. We transformed weight and height data into z-scores using the CDC/NCHS growth charts; defined underweight, stunting, and wasting by z-scores of less than -2 SD; and calculated overweight and obesity, according to the cutoff proposed by the International Obesity Task Force. Socioenvironmental characteristics included housing, public services, parental resources, and farming practices; we processed these variables by categorical principal-component analysis. The two first axes defined four subgroups of schoolchildren: three of these were associated with urban characteristics, while the remaining subgroup was considered rural. Nutritional status differed across groups, whereas overweight was similar among the groups and obesity higher in urban middle-income children. Urban differences were manifested mainly as underweight, but rural children exhibited the greatest stunting and wasting. Thus, the negative effects of environment on nutritional status in children are not restricted to poor periurban and rural areas, though these are indeed unfavorable environments for growth: some urban families provide children with sufficient quantity and diversity of foods to expose them to obesity. By contrast, the more affluent urban families would appear to have greater possibilities for allowing their children to adopt a healthy life-style. Although the causes of differences in nutritional status between middle- and high-income urban groups are not clear, these determinants probably involve economic as well as educational influences.
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PMID:Socioenvironmental conditions and nutritional status in urban and rural schoolchildren. 1825 61

The role of hormonal and metabolic alterations in HIV-associated lipodystrophy syndrome is not yet clear. In patients with HIV-1 undergoing antiretroviral treatment, lipodystrophy is associated with peripheral fat wasting and central adiposity, dyslipidemia, insulin resistance, and increased intramuscular fat accumulation. In HIV lipodystrophy, changes in fat distribution are heterogeneous and can include reduced subcutaneous fat as well as increased visceral fat. In the literature, there is evidence showing that overnight growth hormone (GH) secretion and pulse amplitude decrease in patients with HIV lipodystrophy, with rates of response to standardized GH stimulation being abnormal in at least 20% of these patients. Excess accumulation of visceral fat, central obesity, and increased intra-abdominal adiposity are also typical features of patients with GH deficiency. Recombinant human GH (rhGH) is a potential treatment to diminish excess visceral fat. Our group recently demonstrated that GH therapy in HIV-infected patients with syndromes of fat accumulation produced a significant decrease in body fat and a gain in lean tissue. In this article, we discuss the origin of lipodystrophy in HIV patients, and the use of rhGH treatment (benefits and adverse effects) in HIV-related lipodystrophy.
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PMID:Recombinant human growth hormone: rationale for use in the treatment of HIV-associated lipodystrophy. 1834 7

Loss of function mutations in the receptor tyrosine kinase TrkB pathway resulted in hyperphagia and morbid obesity in human and rodents. Conversely, peripheral or central stimulation of TrkB by its natural ligands BDNF or NT4 reduced body weight and food intake in mice, supporting the idea that TrkB is a key anorexigenic signal downstream of the melanocortin-4 receptor (Mc4r) system. Here we show that in non-human primates TrkB agonists were anorexigenic when applied centrally, but surprisingly orexigenic, leading to gain in appetite, body weight, fat deposits and serum leptin levels, when given peripherally. The orexigenic and pro-obesity effects of peripherally administered TrkB agonists appear to be dose dependent, not associated with fluid retention nor with evidence of receptor down regulation. Our findings revealed that TrkB signaling exerts dual control on energy homeostasis in the primates that could be targeted for the treatment of either wasting disorders or obesity.
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PMID:Appetite enhancement and weight gain by peripheral administration of TrkB agonists in non-human primates. 1838 75

Insulin resistance (IR) and its associated metabolic derangements are known complications of advanced chronic kidney disease (CKD). The etiology of IR in CKD is multifactorial with likely contributions from vitamin D deficiency, obesity, metabolic acidosis, inflammation, and accumulation of 'uremic toxins' leading to acquired defects in the insulin-receptor signaling pathway. An important consequence in end-stage renal disease (ESRD) is its role in the pathogenesis of uremic protein energy wasting, a commonly observed state of metabolic derangement characterized by loss of somatic and visceral protein stores not entirely accounted for by inadequate nutrient intake. In the general population, IR has been associated with accelerated protein catabolism. Among ESRD patients, enhanced muscle protein breakdown has been observed in patients with type 2 diabetes mellitus (DM) compared to ESRD patients without DM. In the absence of DM or severe obesity, IR is detectable in dialysis patients and strongly associated with increased muscle protein breakdown, even after controlling for inflammation. This process appears to be mediated by the ubiquitin-proteasome pathway. Given the high prevalence of protein energy wasting in ESRD and its unequivocal association with adverse clinical outcomes, IR may represent an important modifiable target for intervention in the ESRD population.
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PMID:Determinants of insulin resistance and its effects on protein metabolism in patients with advanced chronic kidney disease. 1845 70

Currently, there are 5 million individuals with chronic heart failure (CHF) in the United States who have poor clinical outcomes, including high death rates. Observational studies have indicated a reverse epidemiology of traditional cardiovascular risk factors in CHF; in contrast to trends seen in the general population, obesity and hypercholesterolemia are associated with improved survival. The temporal discordance between the overnutrition (long-term killer) and undernutrition (short-term killer) not only can explain some of the observed paradoxes but also may indicate that malnutrition, inflammation, and oxidative stress may play a role that results in protein-energy wasting contributing to poor survival in CHF. Diminished appetite or anorexia and nutritional deficiencies may be both a cause and a consequence of this so-called malnutrition-inflammation-cachexia (MIC) or wasting syndrome in CHF. Neurohumoral activation, insulin resistance, cytokine activation, and survival selection-resultant genetic polymorphisms also may contribute to the prominent inflammatory and oxidative characteristics of this population. In patients with CHF and wasting, nutritional strategies including amino acid supplementation may represent a promising therapeutic approach, especially if the provision of additional amino acids, protein, and energy includes nutrients with anti-inflammatory and antioxidant properties. Regardless of the etiology of anorexia, appetite-stimulating agents, especially those with anti-inflammatory properties such as megesterol acetate or pentoxyphylline, may be appropriate adjuncts to dietary supplementation. Understanding the factors that modulate MIC and body wasting and their associations with clinical outcomes in CHF may lead to the development of nutritional strategies that alter the pathophysiology of CHF and improve outcomes.
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PMID:Nutritional and anti-inflammatory interventions in chronic heart failure. 1851 34

The livers of 531 captive wild birds necropsied at the Zoological Society of London were examined histologically. Marked fatty infiltration of the liver was found in 13 cases. Seven of the 13 cases were from the order Psittaciformes indicating that some species (cockatoos, parakeets and parrots) in this order may be particularly susceptible to fatty infiltration of the liver. Affected livers were commonly swollen or enlarged, pale, white or yellow in colour and soft, friable or fatty at post mortem examination. Histologically, marked fatty infiltration of the liver was characterised by the presence of intracytoplasmic fat vacuoles within hepatocytes without zonal or lobular distribution throughout the sections examined. Reticulolysis and fibrosis of the hepatic parenchyma were found in association with marked fatty liver in a proportion of cases. Macroscopic or histological evidence of hepatic haemorrhages was not found in affected birds. In psittacine birds, obesity was frequently seen at post mortem examination and it was considered that nutritional and/or metabolic factors were important causes of fatty liver in this group. Fatty liver was found in association with chronic wasting diseases caused by mycotic infection in two cases.
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PMID:Fatty liver in birds at the Zoological Society of London. 1876 40

The CB1 cannabinoid receptor and its endogenous ligands, the endocannabinoids, are involved in energy balance control, stimulating appetite and increasing body weight in wasting syndromes. Different studies have investigated the relationship between polymorphisms of the cannabinoid receptor 1 (CNR1) gene and obesity with conflicting results. In the present study, we investigated the 1359G/A (rs1049353), 3813A/G (rs12720071) and 4895A/G (rs806368) polymorphisms in the CNR1 gene in a Brazilian population of European descent. To verify the association between these variants and obesity-related traits in this population, 756 individuals were genotyped by PCR-RFLP methods. The 4895G allele was associated with waist to hip ratio (WHR) (P = 0.014; P = 0.042 after Bonferroni correction). An additive effect with the GAA haplotype was associated with WHR (P = 0.028), although this statistical significance disappeared after Bonferroni correction (P = 0.084). No significant association was observed between the genotypes of the 1359G/A and 3813A/G polymorphisms and any of the quantitative variables investigated. Our findings suggest that CNR1 gene polymorphism is associated with central obesity in this Brazilian population of European ancestry.
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PMID:Cannabinoid type-1 receptor gene polymorphisms are associated with central obesity in a Southern Brazilian population. 1877 93

Optimal health and well-being are now considered the true measures of human development. Integrated strategies for infant, child and adult nutrition are required that take a life-course perspective to achieve life-long health. The major nutrition challenges faced today include: (a) addressing the pending burden of undernutrition (low birth weight, severe wasting, stunting and Zn, retinol, Fe, iodine and folic acid deficits) affecting those individuals living in conditions of poverty and deprivation; (b) preventing nutrition-related chronic diseases (obesity, diabetes, CVD, some forms of cancer and osteoporosis) that, except in sub-Saharan Africa, are the main causes of death and disability globally. This challenge requires a life-course perspective as effective prevention starts before conception and continues at each stage of life. While death is unavoidable, premature death and disability can be postponed by providing the right amount and quality of food and by maintaining an active life; (c) delaying or avoiding, via appropriate nutrition and physical activity interventions, the functional declines associated with advancing age. To help tackle these challenges, it is proposed that the term 'malnutrition in all its forms', which encompasses the full spectrum of nutritional disorders, should be used to engender a broader understanding of global nutrition problems. This term may prove particularly helpful when interacting with policy makers and the public. Finally, a greater effort by the UN agencies and private and public development partners is called for to strengthen local, regional and international capacity to support the much needed change in policy and programme activities focusing on all forms of malnutrition with a unified agenda.
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PMID:Conference on "Multidisciplinary approaches to nutritional problems". Rank Prize Lecture. Global nutrition challenges for optimal health and well-being. 1901 8


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