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)

Nutritional modulation of the immune response can be demonstrated both in nutritional deficiency and in obesity. A proportion of obese adolescents and adults showed a variable impairment of cell-mediated immune responses in vivo and in vitro and reduction of intracellular bacterial killing by polymorphonuclear leukocytes. Immunological changes correlated with subclinical deficiencies of iron and zinc, and therapy with these micronutrients for 4 weeks resulted in improvement in immunological responses. In genetically obese mice, the number of mononuclear cells and Thy 1.2-positive lymphocytes in the thymus and the spleen is less compared with that in lean controls. The plaque-forming antibody response is reduced. Natural killer cell activity is increased. Cytotoxic response of spleen cells of obese animals immunized in vivo was markedly lower than that of lean controls, whereas the same response after in vitro sensitization was normal. These data point to the importance of metabolic and nutritional factors in the pathogenesis of altered immunocompetence.
 ...
PMID:Immune response in overnutrition. 726 Sep 49

We have determined the effects of bilateral electrolytic lesions of the ventromedial hypothalamus (VMH) on activity in the hypothalamo-pituitary-adrenal (HPA) system. Acutely, during the first 5 days, lesions of the anterior-medial VMH caused loss of the diurnal rhythms in food intake and plasma corticosterone (B) levels. Plasma B concentrations were elevated during the time of the normal trough of the basal diurnal rhythm in HPA axis activity and the diurnal rhythm in food intake was abolished, in agreement with the results of others. Consistent with hyperactivity in the HPA axis, lesioned rats had increased adrenal weight, decreased thymus and body weights and decreased plasma transcortin concentrations. To determine how lesions of the VMH provoke these increases in activity of the HPA system, the sensitivity of ACTH in adrenalectomized, lesioned rats to replacement with exogenous B was determined under basal conditions during the trough (morning-AM) and peak (evening-PM) of the diurnal rhythm in HPA axis activity. ACTH in lesioned rats in the AM was insensitive to feedback over the very low range of plasma B of 1-4 micrograms/dl, whereas sham-lesioned controls exhibited the normal, high sensitivity of ACTH to B at this time of day. There was no difference between the sensitivity of ACTH to this low range of B in the PM in VMH- and sham-lesioned rats. Two to 5 weeks after VMH lesions, as found by others, mean daily plasma B levels did not differ from sham-lesioned controls; however, plasma B during the AM was still mildly elevated in these rats. Inhibition of plasma B in the PM by dexamethasone was less effective in lesioned rats. Although HPA system responses to hypoglycemia, corticotropin-releasing factor and ACTH were normal, the lesioned rats exhibited obesity, hyperinsulinemia, hyperglycemia, hypertension and tachycardia, all signs consistent with mild hyperactivity of the PHA axis. Occupancy of type I, high-affinity corticosteroid receptors is known to control basal activity of the HPA system during the trough of the diurnal rhythm and to interact with glucocorticoid receptors to affect basal activity during the peak of the diurnal rhythm and during AM stress. We conclude that VMH lesions disrupt transmission of inhibitory signals, mediated by occupancy of type I corticosteroid receptors, that are initiated by a B feed-back site.
 ...
PMID:Ventromedial hypothalamic lesions inhibit corticosteroid feedback regulation of basal ACTH during the trough of the circadian rhythm. 778 59

The metabolism of neutral lipids (free and ester-bound cholesterols, mono-, di- and triacylglycerides) was greatly impaired in liver, spleen, thymus tissues and ileocecal lymph nodes of BALB/c mice with subacute alloxan diabetes (content of sugar in blood was no less than 14 mmol/l) as shown by 3H-acetate and 14C-palmitate incorporation into the corresponding lipid fractions. The rate of neutral lipid turnover was specifically decreased in all the tissues studied. However, a considerable accumulation of these lipid fractions was found in thymus tissue. Incorporation of labelled palmitate into triacylglycerides was increased in the spleen but without obesity of the organ.
 ...
PMID:[Metabolism of neutral lipids in hemopoietic organs and in the liver of mice with alloxan diabetes]. 783 58

Many important lessons have been learned from studies of autoimmune diseases in chicken models. It is now quite clear that both cellular and humoral immune responses are important in developing the final picture of autoimmune disease. In the case of the amelanosis of Smyth line (SL) chickens, antibody appears to play the primary role, whereas the sclerosis of University of California/Davis line-200 (UCD-200) birds is mainly mediated by T cells. Chronic thyroiditis of the OS chicken is due to both humoral and cellular effector mechanisms. The Obese strain (OS) chicken is particularly valuable for studies of genetics. Multiple genetic factors converge in producing maximal susceptibility to the development of autoimmune thyroiditis. They include MHC genes responsible for immune recognition; genes affecting thymus development, critical for regulation of the immune response; and genes that control thyroid function, influencing the vulnerability of the target organ to autoimmune attack. The importance of environmental factors, such as dietary iodine, is also strongly supported by studies in the OS chicken. Thus, the birds have provided valuable clues to our understanding of human autoimmune disorders in the past and are expected to do so in the future.
 ...
PMID:Avian models of autoimmune disease: lessons from the birds. 793 87

The thymic microenvironment (composed of the lymphoepithelial stroma and the secretory products of the thymic epithelium) provides the required milieu for the development of the thymus-derived lymphocytes (T cells). There is limited information characterizing or identifying the active secretory components of the avian thymus. The work discussed here has focused on examination of the presence, regulation, and activity of one of the thymic hormones (thymulin) in the chicken. A thymulin-like product has been shown to exist in chicken serum as assessed by the mammalian bioassay and an ELISA immunoassay; thymectomy removes this product from the serum. Serum thymulin activity has been shown to be directly related to the thyroid status of the chick with the functionally hypothyroid Cornell sex-linked dwarf strain having lower levels than the euthyroid K strain. Alterations in circulating thymulin concentrations produced by daily thymulin injections resulted in an altered profile of the major peripheral blood T cell subpopulations and produced significant changes in the autoimmune pathology present within the Obese strain chicken. These approaches represent preliminary attempts to study the role of thymulin in avian immune development and in immune-neuroendocrine interactions.
 ...
PMID:The humoral activity of the avian thymic microenvironment. 834 55

Although obese animals are more susceptible to infection, the underlying causes are not fully known. In this study, long-term measurements were made of lymphocyte subsets in peripheral blood, spleen, and thymus in genetically obese Zucker (fa/fa) rats. Blastogenic response of splenocytes to mitogens was also examined. fa/fa rats developed obesity, hyperlipidemia, and hyperinsulinemia after 5 weeks of age. Flow cytometric analysis revealed that T cells in peripheral blood, spleen, and thymus were all reduced significantly in obese rats after 8 weeks of age compared to nonobese (Fa/-) littermates. All T-cell subsets examined, including CD4+ and CD8+ T cells, were similarly reduced in spleen and thymus as well as in peripheral blood with advance in age. In addition, proliferative responses of splenocytes to mitogens were significantly low in obese rats. These results indicate that long-term obesity may reduce the size of the T-cell pool and impair the responsiveness of splenocytes in rats.
 ...
PMID:T lymphopenia in genetically obese rats. 947 85

According to our concept, the development of autoimmune disease depends on the presence of two sets of essential genes, one coding for an abnormal autoreactivity of the immune system, the other for a primary susceptibility of the target organ/structure for the immune attack. The final outcome of the disease in a given individual is then fine tuned by modulatory factors, such as diet or hormones. With regard to the latter, the immuno-endocrine interaction via the hypothalamo-pituitary-adrenal (HPA) axis has proven to be of special importance. Investigating the so-called Obese strain (OS) of chickens, an animal model with a spontaneously occurring Hashimoto-like autoimmune thyroiditis, we have first shown an impaired surge of glucocorticoid hormones after stimulation of the HPA axis by antigens or certain cytokines (glucocorticoid-increasing factors--GIFs). More recently, we have found a similar behavior in models with systemic autoimmune diseases, that is, murine lupus erythematosus and avian scleroderma. More detailed studies have, however, proven that the mechanisms underlying this altered immuno-endocrine communication via the HPA axis differs in different models. Finally, recent data point to the possibility that the classical pathways of glucocorticoid-T-cell interactions also take place in the thymus itself, which has been shown to be a site of steroid hormone production.
 ...
PMID:Neuroendocrine-immune disturbances in animal models with spontaneous autoimmune diseases. 962 86

Plasmolipin is a membrane protein and belongs to the tetraspan molecule (4TM) family, an expanding group of myelin proteins many of which could be linked to human hereditary demyelinating neuropathies. We have cloned and sequenced the mouse plasmolipin gene, revealing the common organization of the 4TM gene group with four exons and a large first intron. Western blot analysis with an antibody raised against the C-terminal intracellular part of the protein showed that plasmolipin is expressed not only in the nervous system and kidney, but also in a number of other tissues such as thymus, testis, lung, and thyroid gland. By means of radiation hybrid mapping and FISH analysis, we could localize the human plasmolipin gene to Chromosome 16q13 within the putative region of the Bardet-Biedl syndrome type 2 (BBS2) gene locus. BBS2 is a clinically and genetically heterogeneous group of disorders resulting in rod-cone dystrophy, obesity, postaxial polydactyly, renal dysfunction, and mental retardation, which were very recently associated with a novel gene designated BBS2. With respect to intrafamiliar variations in the manifestation of BBS, we suggest that plasmolipin might be either another candidate gene or a modifier of the BBS2 phenotype.
 ...
PMID:Plasmolipin: genomic structure, chromosomal localization, protein expression pattern, and putative association with Bardet-Biedl syndrome. 1170 81

The implication of regulatory T cells in self-tolerance induction was shown in experimental models based on construction of thymic chimera and peripheric T cell transfers. The role played by the epithelial stroma of the thymus in CD4+ regulatory T cell selection was demonstrated. In the NOD (Non Obese Diabetic) strain, protection again diabetes was obtained by grafting supplementary thymuses injected with allogeneic pancreatic islets. This result suggest that the NOD thymuses are defective in the production of T regulatory cells.
 ...
PMID:[Regulatory phenomena in tolerance induction]. 1264 91

Small size at birth has been associated with an increased risk of central obesity and reduced lean body mass in adult life. This study investigated the time of onset of prenatally induced obesity, which occurs after maternal feed restriction, in the guinea pig, a species that, like the human, develops substantial adipose tissue stores before birth. We examined the effect of maternal feed restriction [70% ad libitum intake from 4 wk before to midpregnancy, then 90% until day 60 gestation (term approximately 69 days)] on fetal growth and body composition in the guinea pig. Maternal feed restriction reduced fetal (-39%) and placental (-30%) weight at 60 days gestation and reduced liver, biceps muscle, spleen, and thymus weights, relative to fetal weight, while relative weights of brain, lungs, and interscapular and retroperitoneal fat pads were increased. In the interscapular depot, maternal feed restriction decreased the volume density of multilocular fat and increased that of unilocular fat, resulting in an increased relative weight of interscapular unilocular fat. Maternal feed restriction did not alter the relative weight of perirenal fat or the volume density of adipocyte populations within the depot but increased unilocular lipid locule size. Maternal feed restriction in the guinea pig is associated with decreased weight of major organs, including liver and skeletal muscle, but increased adiposity of the fetus, with relative sparing of unilocular adipose tissue. If this early-onset obesity persists, it may contribute to the metabolic and cardiovascular dysfunction that these offspring of feed-restricted mothers develop as adults.
 ...
PMID:Chronic maternal feed restriction impairs growth but increases adiposity of the fetal guinea pig. 1547 10


<< Previous 1 2 3 4 5 6 7 Next >>