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

Surgical removal of the olfactory bulbs (OB) was performed in mature male red-winged blackbirds, maintained under a short-day light regime. Bulbectomy caused hyperphagia, which was not accompanied by obesity. Bulbectomized (OBX) birds had incresaed thyroid follicular activity and had greater developed testes than sham-operated controls. In the adenohypophyses of the OB-removed birds there was an increase in the populations of 4 types of chromophils: alcianophils, PAS-positive basophils, orangeophils and PAS-positive acidophils. The possibility that the OB are involved in the photoperiodic regulation of the activity of the gonads and thyroids is discussed.
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PMID:The involvement of the olfactory bulbs in the regulation of gonadal and thyroidal activities of male red-winged blackbirds, exposed to short-day light regime. 48 90

The contribution of obesity and/or diabetes to liver pathology in the morbidly obese patient is controversial. We studied the liver biopsies of 100 consecutive patients undergoing gastric bypass surgery for morbid obesity. Multiple morphologic parameters were analyzed and graded independently, without knowledge of the clinical history, liver function tests, and oral glucose tolerance results of the patients. Six percent of the entire group demonstrated no fat, 42% mild fat, 20% moderate fat, and 24% severe fatty metamorphosis of the liver. Twenty-three percent of the patients had central vein fibrosis, 23% sinusoidal fibrosis, 19% bridging fibrosis, and 4% cirrhosis. Thirty-six percent of the patients had some degree of steatohepatitis, 66% possessed so-called glycogen nuclei of hepatocytes, 6% had PAS-positive thickening of blood vessels in the portal tracts, and 1% had lipogranulomas. The degree of fatty metamorphosis and fibrosis was analyzed in three separate groups, categorized by the glycemic status of the patient: 46 patients with normal glucose tolerance (NGT), 23 patients with impaired glucose tolerance (IGT), and 31 patients with non-insulin-dependent diabetes mellitus (NIDDM). Increasing severity of fatty metamorphosis from the normoglycemic obese to the diabetic obese patients was found, which was statistically significant by chi 2 analysis. Four of the six patients showing no fatty metamorphosis were normoglycemic. Glycogen nuclei and PAS-positive blood vessels were significantly more prevalent in the diabetic obese than in the normal obese. In conclusion, the distribution of significant liver histopathology in the morbidly obese patient correlates in severity with the degree of impaired glycemic status.
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PMID:Liver pathology in morbidly obese patients with and without diabetes. 153 87

Glycoregulation and insulin secretion abnormalities and micro-angiopathy were systematically investigated in 46 patients (6 men and 40 women; mean age 34.8) seeking medical attention for obesity. In all patients, a three-hour oral glucose tolerance test (OGTT) with 50 g glucose, with concomitant plasma insulin determinations, Hb A1c assay and skin biopsy (SB) at the medial aspect of the arm (optic microscopy study, PAS stain) were performed. We obtained 46 Hb A1c assays, 45 OGTT, 43 insulin determinations and 42 SB. In 40 patients, all four studies were available. We consider as abnormal blood glucose greater than 7.8 mmol at 120 mn with intermediate measurement greater than 10.1, insulin greater than 64 mcU with a maximum delayed after the 60th mn, Hb A1c greater than 6.3% and SB score greater than 10 (evaluating basement membrane thickness, endothelium swelling, aspect of pericytes, perivascular infiltration and percentage of capillaries involved). We observed 6 abnormal OGTT, 12 dysinsulinisms (DI), 5 Hb A1c greater than 6.3% and 17 SB greater than or equal to 10 with typical diabetic microangiopathy. Out of 40 fully investigated patients, 14 were normal for all criteria, 12 had only one abnormality (12 SB, 5 DI, 1 OGTT), 6 had 2 abnormalities (2 SB + DI, OGTT + DI, SB + OGTT, SB + Hb A1c, DI + Hb A1c) and 2 had 3 abnormalities (SB + DI + Hb A1c, OGTT + DI + Hb A1c).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Detection of diabetes in obese patients. Systematic study of induced hyperglycemia with assays of blood insulin, glycosylated hemoglobin A1c and cutaneous biopsy in 46 patients]. 632 Apr 20

We developed an animal model for non-insulin-dependent diabetes mellitus, a genetically obese rat strain, Wistar fatty. These rats show obesity-related features such as hyperinsulinemia and hyperlipemia, and only males develop diabetic features including hyperglycemia, glucoseuria and polyuria as they age. Histopathological study demonstrated a deposition of PAS-positive granules in the epithelial cells and a diffuse thickening of the mesangial area and moderate changes of the renal tubules. We found that ICAM-1 is expressed on the glomeruli of male Wistar fatty rats and the expression is associated with the development of nephropathy; it is weak at 5 weeks, becomes markedly strong at 15 weeks and progresses further at 29 weeks of age. We tried in vivo administration of monoclonal antibody, anti-ICAM-1 alone or together with anti-LFA-1 into male Wistar fatty rats during the period from 5 weeks to 17 weeks of age. The treatment, however, could not prevent the development of nephropathy. ICAM-1 expressed on the glomeruli of Wistar fatty rats seems not to play a key role in development of the nephropathy by mediating leukocyte infiltration. It will be a useful marker of the development of the disease.
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PMID:Expression of ICAM-1 on glomeruli is associated with progression of diabetic nephropathy in a genetically obese diabetic rat, Wistar fatty. 880 76

Previous studies showed that the 139H strain of scrapie injected intra-cerebrally in hamsters caused obesity, and extensive histopathological changes in islets of Langerhans and pituitaries. In the current study, we report that an abnormal granular substance, which stained positively with periodic acid-Schiff (PAS-positive substance; PPS), was found in the islets of Langerhans, pituitaries, adrenal glands, in the lumens of blood vessel cores (BVCs) and in blood vessels in 139H-infected hamsters, but not in either 263K-infected or control hamsters. This substance was found in the endocrine organs, forming grape-like or plaque-like structures, which were small, round to ovoid, and homogenous measuring up to 7 microns in diameter and usually grouped in clusters. PPS was not found in the brains of control or scrapie-infected hamsters. Using immunostaining for amyloid protein (PrP, beta A4), as well as Congo red and thioflavin-S stains, no evidence was found of amyloid plaque formation in the islets of Langerhans, the adrenal glands, or the pituitaries of 139H- or 263K-infected hamsters. PPS might relate to the pathological changes in the endocrine organs in 139H-infected hamsters.
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PMID:Abnormal periodic acid-Schiff (PAS)-positive substance in the islets of Langerhans, pituitaries and adrenal glands of 139H scrapie-infected hamsters. 1042 34

Studies of mice and humans have revealed a number of genes that when mutated result in severe obesity. We have studied a unique girl with early-onset obesity and a de novo balanced translocation between chromosomes 1p22.1 and 6q16.2. Her weight gain is most likely due to excessive food intake, since measured energy expenditure was normal. We cloned and sequenced both translocation breakpoints. The translocation does not appear to affect any transcription unit on 1p, but it disrupts the SIM1 gene on 6q. SIM1 encodes a human homolog of Drosophila Sim (Single-minded), a transcription factor involved in midline neurogenesis, and is a prototypical member of the bHLH-PAS (basic helix-loop-helix + period, aryl hydrocarbon receptor, Single-minded) gene family. Our subject's trans- location separates the 5' promoter region and bHLH domain from the 3' PAS and putative transcriptional regulation domains. The transcriptional targets of SIM1 are not known. Mouse Sim1 is expressed in the developing kidney and central nervous system, and is essential for formation of the supraoptic and paraventricular (PVN) nuclei of the hypothalamus. Previous neuroanatomical and pharmacological studies have implicated the PVN in the regulation of body weight: PVN neurons express the melanocortin 4 receptor and appear to be physiological targets of alpha-melanocyte-stimulating hormone, which inhibits food intake. We hypothesize that haploinsufficiency of SIM1, possibly acting upstream or downstream of the melanocortin 4 receptor in the PVN, is responsible for severe obesity in our subject.
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PMID:Profound obesity associated with a balanced translocation that disrupts the SIM1 gene. 1058 84

The bHLH-PAS transcription factor SIM1 is required for the development of the paraventricular nucleus (PVN) of the hypothalamus. Mice homozygous for a null allele of Sim1 (Sim1(-/-)) lack a PVN and die perinatally. In contrast, we show here that Sim1 heterozygous mice are viable but develop early-onset obesity, with increased linear growth, hyperinsulinemia and hyperleptinemia. Sim1(+/-) mice are hyperphagic but their energy expenditure is not decreased, distinguishing them from other mouse models of early-onset obesity such as deficiencies in leptin and melanocortin receptor 4. Quantitative histological comparison with normal littermates showed that the PVN of Sim1(+/-) mice contains on average 24% fewer cells without a selective loss of any identifiable major cell type. Since acquired lesions in the PVN also induce increased appetite without a decrease in energy expenditure, we propose that abnormalities of PVN development cause the obesity of Sim1(+/-) mice. Severe obesity was described recently in a patient with a balanced translocation disrupting SIM1. Pathways controlling the development of the PVN thus have the potential to cause obesity in both mice and humans.
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PMID:Sim1 haploinsufficiency causes hyperphagia, obesity and reduction of the paraventricular nucleus of the hypothalamus. 1144 38

SIM1 and ARNT2 are two basic helix-loop-helix/PAS (Per-Arnt-Sim) transcription factors that control the differentiation of neuroendocrine lineages in the mouse hypothalamus. Heterozygous Sim1 mice also develop early onset obesity, possibly due to hypodevelopment of the hypothalamus. Although SIM1 and ARNT2 form heterodimers to direct the same molecular pathway, knowledge of this pathway is limited. To facilitate the identification of their downstream genes, we combined an inducible gene expression system in a neuronal cell line with microarray analysis to screen for their transcriptional targets. This method identified 268 potential target genes of SIM1/ARNT2 that displayed >1.7-fold induced expression. 15 of these genes were subjected to Northern analysis, and a high percentage of them were confirmed to be up-regulated. In vivo, several of these genes showed neuroendocrine hypothalamic expression correlating with that of Sim1. Furthermore, we found that expression of two of these potential targets, the Jak2 and thyroid hormone receptor beta2 genes, was lost in the neuroendocrine hypothalamus of the Sim1 mutant. The expression and predicted functions of many of these genes provide new insight into both the Sim1/Arnt2 action in neuroendocrine hypothalamus development and the molecular basis for the Sim1 haplo-insufficient obesity phenotype.
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PMID:Identification of the downstream targets of SIM1 and ARNT2, a pair of transcription factors essential for neuroendocrine cell differentiation. 1294 13

Obesity, which results from adipose differentiation and adipocyte hypertrophy, is a primary risk factor of these life-style-diseases. Obesity, is primary risk factor of these life-style-diseases, results from adipose differentiation and adipocyte hypertrophy. Adipose differentiation is regulated by several transcriptional factors, and we have focused here on the roles played by endothelial PAS domain protein1 (EPAS1) in adipogenesis. EPAS1 was identified as a factor responsible for hypoxia responses, such as angiogenesis, here we demonstrated that EPAS1 is highly induced during adipose differentiation in vivo and in vitro. We then analyzed EPAS1 promoter activity during adipose differentiation in 3T3-L1 cells. We showed that the sequence -478/-445 is responsible for the up-regulation of EPAS1 expression during adipose differentiation and that the activity of this region is controlled by Sp1 and Sp3. To examine whether EPAS1 exerts an influence on adipogenesis, we overexpressed dominant negative form of EPAS1 in 3T3-L1 cells. The expression of EPAS1 (1-485) allowed cells to accumulate only a minimum amount of lipid droplets. Therefore, induction of EPAS1 expression is necessary for execution of adipose differentiation program. The mechanism involves the direct transcriptional regulation of Glut1, Glut4 and IRS3 genes by EPAS1. These results also confirmed that the protein level of EPAS1 was increased by insulin stimulation in adipocytes. Taken together, this result also indicated that EPAS1 plays a role in the part of insulin action. Therefore, these results suggest that the quantitative and functional alteration of EPAS1 are involved in metabolic syndrome occurrence.
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PMID:[Transcription factor EPAS1 regulates insulin signaling pathway]. 1720 95

Fatty liver in obese patients is emerging as one of the most common causes of chronic liver disease. Obese patients are at risk of developing type 2 diabetes mellitus (DM), and aggravating non-alcoholic fatty liver disease (NAFLD), developing into steatohepatitis (NASH) and hepatic fibrosis. Little is known of the possible impact on liver fibrogenesis of diabetes type 2 associated with obesity and NAFLD. Fifty-two morbidly obese patients were evaluated with complete clinical and laboratory medical assessment. Liver biopsy material was fixed in formalin, routinely processed to paraffin blocks, cut into 4-microm sections, stained with HE, PAS, Masson's trichrome and reticulin. Immunohistochemical stains included collagen IV, SMA and laminin. Within the initial group of 52, 25 patients had DM type 2, mean age 45.8 years. Patients with diabetes were older; had higher BMI, liver enzyme tests, glucose, cholesterol, and triglycerides; and lower albumin concentration. Livers of diabetics had significantly more severe steatosis and rich perisinusoidal collagen IV, laminin and SMA accumulation without histologically detectable NASH and irrespective of the degree of steatosis. Obese patients with type 2 DM and insulin resistance develop more severe NAFLD and early sinusoidal fibrosclerosis.
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PMID:Fibrogenesis in fatty liver associated with obesity and diabetes mellitus type 2. 1784 88


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