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

Estrogen biosynthesis in adipose tissue increases with age and obesity, and has been implicated in the development of endometrial cancer and breast cancer. In normal human adipose tissue, expression of the CYP19 gene which encodes aromatase P450, the enzyme responsible for estrogen biosynthesis, is regulated by a distal promoter, namely promoter I.4. Stimulation of expression in adipose stromal cells by members of the type 1 cytokine family, i.e. interleukin (IL)-6, IL-11, leukemia inhibitory factor (LIF) and oncostatin M (OSM), is mediated via a Jak-STAT3 signaling pathway and a GAS element upstream of promoter I.4. In contrast, aromatase expression in breast adipose tissue proximal to tumor is increased three- to four-fold to the utilization of another promoter, namely promoter II, proximal to the translation initiation site. In the present report, we show that prostaglandin (PG) E2 is the most potent factor which stimulates aromatase expression via cyclic AMP and promoter II. PGE2 acts via EP1 and EP2 receptor subtypes to stimulate both the PKC and PKA pathways. The combined stimulation of both of these pathways results in the maximal expression of promoter II-specific CYP19 transcripts. Because PGE2 is a major secretory product both of breast tumor epithelial cells and fibroblasts, as well as of macrophages infiltrating the tumor site, then this could be the mechanism whereby estrogen biosynthesis is stimulated in breast sites adjacent to a tumor, leading in turn to increased growth and development of the tumor itself.
J Steroid Biochem Mol Biol 1997 Apr
PMID:Transcriptional regulation of CYP19 gene (aromatase) expression in adipose stromal cells in primary culture. 936 91

Obesity is a highly prevalent disease that carries enormous human and economic costs in western nations. The complexity and diversity of the paths leading to an overweight or an obesity status are enormous. The etiology, causes, associated morbidity, treatment, benefits versus risks of weight loss, prevention, and other aspects of obesity are all highly complex and intimately associated with other diseases, the prevalence of which is augmented by our present way of life. This article gives a brief overview of the current status of knowledge of the genetic basis of human obesity from a genetic epidemiology, experimental genetic and molecular biology perspective. It appears likely that the susceptibility to obesity depends, to a large extent, on several autosomal genes.
Mol Med Today 1995 Apr
PMID:The genetics of obesity: from genetic epidemiology to molecular markers. 941 38

The effects of both dietary obesity and a food deprivation period of 24 hours on fatty acid composition of brown adipose tissue have been investigated. Long time exposure to a hypercaloric high-fat diet such as the cafeteria diet induced an important tissue fatty acid accumulation, mainly for the major saturated and monounsaturated fatty acids. Notable metabolic differences have been observed in the behaviour of control and obese rats facing a food deprivation period: a preferential utilization of the most abundant saturated fatty acids in control rats and a minor response in obese rats, with a greater fat accumulation in the interscapular brown adipose tissue.
Biochem Mol Biol Int 1997 Dec
PMID:Fatty acid composition of brown adipose tissue in dietary obese rats. 941 22

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a transcription factor implicated in adipocyte differentiation, lipid and glucose metabolism. A polymorphism corresponding to a silent C-->T substitution was detected in exon 6 of the PPAR gamma gene. We analysed the relationships between this genetic polymorphism and various markers of the obesity phenotype (body weight, body mass index, waist:hip ratio and plasma leptin levels) in a representative sample of 820 men and women living in northern France. The frequencies of the C and T alleles were 0.860 and 0.140 respectively. In the whole sample no association of the polymorphism with the markers tested was observed but a statistically significant interaction ( P < 0.03) existed between this polymorphism and body mass index for plasma leptin levels. This result suggested that the impact of the PPAR gamma gene polymorphism on plasma leptin levels differed according to the BMI of the subjects. Indeed, obese subjects (BMI >30 kg/m2) bearing at least one T allele ( CT + TT ) had higher plasma leptin levels than subjects who did not (35.0 +/- 17.4 ng/ml versus 28.3 +/- 14.8 ng/ml respectively; P < 0.001). This effect existed in both genders, despite the higher plasma leptin levels observed in women. The plasma leptin level increase was not associated with elevation of body mass index, even though these two variables were highly correlated. Thus for a given leptin level the BMI was relatively lower in obese subjects carrying at least one T allele than in obese CC homozygotes. Our results show that in obese subjects variability within the PPAR gamma gene locus is associated with circulating leptin levels and may modify the relationship between leptin levels and adipose tissue mass.
Hum Mol Genet 1998 Mar
PMID:A genetic polymorphism of the peroxisome proliferator-activated receptor gamma gene influences plasma leptin levels in obese humans. 946 1

1. Studies of the regulation of neurosecretory cell gene expression suffer from the lack of suitable cell lines. Two approaches have been used to overcome this deficit: transfection of neuropeptide genes into heterologous cell lines and generation of transgenic animals. 2. Studies with heterologous cell lines have revealed the potential involvement of nuclear hormone receptors, POU proteins, and fos/jun/ATF family members in the regulation of the vasopressin and oxytocin genes. Although limited in their scope, these studies have contributed greatly to the dissection of basic properties of elements in the vasopressin and oxytocin gene promoters. 3. Transgenic mice, and more recently rats, have been used to elucidate genomic regions governing cell specificity and physiological regulation of neurosecretory gene expression. The genes encoding the neuropeptides vasopressin and oxytocin have been used in many transgenic studies, due to the well-defined expression patterns and physiology of the endogenous neuropeptides. Cell-specific and physiologically regulated expression of these transgenes has been achieved, demonstrating the action of putative repressor elements and regulation of the expression of one gene by sequences present in the other gene. 4. Appropriate expression and translation of transgenes have resulted in the production of several useful systems. Expression of oncogene sequences in gonadotropin-releasing hormone neurons has allowed the development of cell lines from the resulting tumors, overproduction of corticotropin-releasing factor has produced animal models of anxiety and obesity, and directed ectopic expression of growth hormone has generated a potentially useful rat model of dwarfism. These and other animal models of human disease will provide important avenues for the development of therapeutic strategies.
Cell Mol Neurobiol 1998 Apr
PMID:Transgenic and transcriptional studies on neurosecretory cell gene expression. 953 88

Approximately one-third of Americans are classified as obese. There has long been an interest in drug therapies for obesity. Interest in obesity research and in drug interventions in obesity has greatly increased since the discovery of a protein named leptin, one of apparently many competing biological signals in energy metabolism. The complexity of the obesity problem demands new non-invasive and non-destructive methods for monitoring lipid metabolism and energy expenditure to study the competing biological signals and their effects. A new computer algorithm for spectrometric imaging of living subjects is used to remove artifacts arising from subject motion from spectra and images. The algorithm is sufficiently simple to be implemented easily in hardware for real-time video processing. Because the algorithm can be applied to images, thermogenesis and lipid metabolism in interscapular adipose tissue can be observed directly in unrestrained and unanesthetized subjects using an InSb focal plane array video camera. The accuracy and precision of temperature and spectral measurements are established using laboratory references and prototype drugs in test subjects.
Cell Mol Biol (Noisy-le-grand) 1998 Feb
PMID:Near-IR and IR imaging in lipid metabolism and obesity. 955 37

Protein-tyrosine phosphatases (PTPases) have been implicated in the physiological regulation of the insulin signalling pathway. In cellular and molecular studies, the transmembrane, receptor-type PTPase LAR and the intracellular, non-receptor enzyme PTP1B have been shown to have a direct impact on insulin action in intact cell models. Since insulin signalling can be enhanced by reducing the abundance or activity of specific PTPases, pharmaceutical agents directed at blocking the interaction between individual PTPases and the insulin receptor may have potential clinical relevance to the treatment of insulin-resistant states such as obesity and Type II diabetes mellitus.
Mol Cell Biochem 1998 May
PMID:Regulation of the insulin signalling pathway by cellular protein-tyrosine phosphatases. 960 18

The pathophysiologic importance of insulin resistance in diseases such as obesity and diabetes mellitus has led to great interest in defining the mechanism of insulin action as well as the means to overcome the biochemical defects responsible for the resistance. Vanadium compounds have been discovered to mimic many of the metabolic actions of insulin both in vitro and in vivo and improve glycemic control in human subjects with diabetes mellitus. Apart from its direct insulinmimetic actions, we found that vanadate modulates insulin metabolic effects by enhancing insulin sensitivity and prolonging insulin action. All of these actions appear to be related to protein tyrosine phosphatase (PTP) inhibition. However, in contrast to its stimulatory effects, vanadate inhibits basal and insulin-stimulated system A amino acid uptake and cell proliferation. The mechanism of these actions also appears to be related to PTP inhibition, consistent with the multiple roles of PTPs in regulating signal transduction. While the precise biochemical pathway of vanadate action is not yet known, it is clearly different from that of insulin in that the insulin receptor and phosphatidylinositol 3'-kinase do not seem to be essential for vanadate stimulation of glucose uptake and metabolism. The ability of vanadium compounds to 'bypass' defects in insulin action in diseases characterized by insulin resistance and their apparent preferential metabolic versus mitogenic signaling profile make them attractive as potential pharmacological agents.
Mol Cell Biochem 1998 May
PMID:Multifunctional actions of vanadium compounds on insulin signaling pathways: evidence for preferential enhancement of metabolic versus mitogenic effects. 960 20

While the causes of obesity remain elusive, the relationship between obesity and insulin resistance is a well-established fact [1]. Insulin resistance is defined as a smaller than normal response to a certain dose of insulin, and contributes to several pathological problems of obese patients such as hyperlipidemia, arteriosclerosis and hypertension. Several pieces of evidence indicate that the cytokine tumor necrosis factor a (TNF-alpha) is an important player in the state of insulin resistance observed during obesity. In this review we will try to summarize what is known about the function of TNF-alpha in insulin resistance during obesity and how TNF-alpha interferes with insulin signaling.
Mol Cell Biochem 1998 May
PMID:TNF-alpha and insulin resistance: summary and future prospects. 960 26

Leptin affects food intake and body weight by actions on the hypothalamus. Although leptin resistance is common in obesity, mechanisms have not been identified. We examined the effect of leptin on expression of the suppressors-of-cytokine-signaling (SOCS) family of proteins. Peripheral leptin administration to ob/ob, but not db/db mice, rapidly induced SOCS-3 mRNA in hypothalamus, but had no effect on CIS, SOCS-1, or SOCS-2. A leptin-dependent increase of SOCS-3 mRNA was seen in areas of hypothalamus expressing high levels of the leptin receptor long form. In mammalian cell lines, SOCS-3, but not CIS or SOCS-2, blocked leptin-induced signal transduction. Expression of SOCS-3 mRNA in the arcuate and dorsomedial hypothalamic nuclei is increased in Ay/a mice, a model of leptin-resistant murine obesity. In conclusion, SOCS-3 is a leptin-inducible inhibitor of leptin signaling, and a potential mediator of leptin resistance in obesity.
Mol Cell 1998 Mar
PMID:Identification of SOCS-3 as a potential mediator of central leptin resistance. 966 Sep 46


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