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)

Infertility and hypercytolipidemic utero-ovarian involution are recognized consequences of the diabetes-obesity syndrome (DOS) in C57BL mice with either obese (ob/ob) or diabetes (db/db) single gene mutations. We have evaluated the interdependent deleterious influences of both mutation types and differences in the genomic background on utero-ovarian dysfunction in C57BL mice. Control ( +/?) C57BL mice were matched with littermate ob/ob and db/db mutants expressed on either the /KsJ or /6 background. Both ob/ob and db/db mutations increased body weights of /KsJ and /6 background strains relative to +/? groups. In contrast, uterine and ovarian weights were depressed by ob/ob and db/db mutations relative to +/?, regardless of the background strain, but especially when expressed on the /KsJ background. Functionally, both ob/ob and db/db mutations induced hyperglycemic-hyperinsulinemic states coupled with depressed serum estradiol-17-beta and progesterone concentrations when expressed on a /KsJ background. Microscopic analysis of utero-ovarian tissue samples revealed marked hypercytolipidemia in the follicular granulosa and endometrial epithelial tissue layers of both ob/ob and db/db mutant groups relative to normal +/? cytoarchitecture. The db/db mutation consistently promoted more severe hypercytolipidemic profiles than the ob/ob mutation, regardless of background strain. Thus, the severity of utero-ovarian hypercytolipidemia following the expression of ob/ob and db/db mutations in C57BL mice is influenced, or moderated, by the genomic background on which the mutation is expressed.
 ...
PMID:Genomic modulation of diabetes (db/db) and obese (ob/ob) mutation-induced hypercytolipidemia: cytochemical basis of female reproductive tract involution. 1502 41

This study was performed to investigate the serum levels of bisphenol A (BPA), an endocrine disruptor, in women with ovarian dysfunction and obesity. Fasting serum samples were obtained from 19 non-obese and 7 obese women with normal menstrual cycles: 7 patients with hyperprolactinemia, 21 patients with hypothalamic amenorrhea, and 13 non-obese and 6 obese patients with polycystic ovary syndrome (PCOS). BPA was measured by an enzyme-linked immunosorbent assay. BPA was detected in all human sera. Serum BPA concentrations were significantly higher in both non-obese and obese women with polycystic ovary syndrome (1.05 +/- 0.10 ng/ml, 1.17 +/- 0.16 ng/ml; p<0.05, respectively) and obese normal women (1.04 +/- 0.09 ng/ml, p<0.05) compared with those in non-obese normal women (0.71 +/- 0.09 ng/ml). There was no difference among women with hyperprolactinemia, women with hypothalamic amenorrhea, and non-obese normal women. There were significant positive correlations between serum BPA and total testosterone (r = 0.391, p<0.001), free testosterone (r = 0.504, p<0.001), androstenedione (r = 0.684, p<0.001), and DHEAS (r = 0.514, p<0.001) concentrations in all subjects. These findings show that there is a strong relationship between serum BPA and androgen concentrations, speculatively due to the effect of androgen on the metabolism of BPA.
 ...
PMID:Positive relationship between androgen and the endocrine disruptor, bisphenol A, in normal women and women with ovarian dysfunction. 1511 66

The current consensus on diagnostic criteria of polycystic ovary syndrome has concluded that it is a syndrome of ovarian dysfunction along with hyperandrogenism and morphology of polycystic ovary. The clinical manifestations may include irregular menses, androgen excess, and obesity, but insulin resistance is also a common feature. There is an increased risk of type 2 diabetes mellitus. Treatment of polycystic ovary includes ovulation induction, amelioration of androgen signs and correction of insulin resistance.
 ...
PMID:[Current criterion for diagnosing polycystic ovary syndrome]. 1546 47

Increased life expectancy leads to increased age-associated health issues in both sexes. For menopausal women the most important of these appear to result from the severe estrogen deficiency caused by ovarian dysfunction. The consequences among others include hot flashes, osteoporosis, obesity, impaired memory, higher incidence of Alzheimer's disease and cardiovascular disease. Ovarian function and steroidogenesis are influenced by pituitary gonadotropins, including follicle-stimulating hormone (FSH), whose actions are mediated through ovarian receptors. This article highlights our recent data pertinent to aging as derived from a novel genetically modified animal model [the FORKO mouse (FOllitropin Receptor KnockOut) lacking the FSH receptor. FORKO female mice experience a chronic depletion of estrogen (E2) from early development, and have phenotypes similar to aging women, with ovarian failure, obesity, skeletal changes, and ovarian tumors. A variety of findings support the conclusion that E2 deficiency in FORKO mice is responsible for their neural impairments associated with glial cell hypertrophy, region-specific brain cells loss, and abnormal behavior. Findings from mice with FSH receptor haploinsufficiency mice ('menopausal mice') are also shedding light on the molecular basis of menopausal conditions that include degeneration of the hippocampus. Many phenotypes noted in the null condition also occur in +/- females but in an age related manner. Thus, the FORKO mouse becomes an excellent model to investigate mechanisms underlying age-related changes especially when these events are accelerated, as in menopausal women. Opportunities abound to assess the potential benefits/adverse effects of hormone replacement regimen on various targets.
 ...
PMID:Perspectives on reproductive senescence and biological aging: studies in genetically altered follitropin receptor knockout [FORKO] mice. 1558 83

In mammals, triacylglycerol (TAG) accumulation in nonadipose tissue, termed lipotoxicity, develops with obesity and can provoke insulin resistance, overt diabetes, and ovarian dysfunction. Leptin, an adipose tissue hormone, may mediate these effects. Feed-satiated broiler breeder hens manifest lipotoxicity-like symptoms. Changes in body and organ weights, hepatic and plasma TAG, nonesterified fatty acids (NEFA), ovarian morphology, and egg production in response to acute voluntary increases of feed intake were measured in 2 studies with Cobb 500 broiler breeder hens provided with either 145 or > or = 290 g of feed/d per hen for 10 d. In both studies, no hen fed 145 g of feed/d exhibited ovarian abnormalities, whereas approximately 50% of feed-satiated hens did. Egg production in feed-satiated hens was reduced from 73.3 to 55.8% (P = 0.001). Morphology indicated that apoptosis-induced atresia occurred in the hierarchical follicles. Fractional weight of yolk increased from 29.3 to 30.6% (P = 0.016) and no longer correlated to egg weight. Body, liver, and abdominal adipose weights were significantly greater (P < 0.05) in feed-satiated hens, as were plasma concentrations of glucose, NEFA, TAG, insulin, and leptin (P < 0.05). Feed-satiated hens with abnormal ovaries had significantly more liver and abdominal fat, greater plasma leptin and TAG concentrations, and more saturated fatty acids in plasma NEFA than did feed-satiated hens with normal ovaries. Differences in severity of lipotoxic metabolic and hormonal responses among feed-satiated hens were closely linked to the incidence of ovarian abnormalities and granulosa cell susceptibility to apoptosis and necrosis.
 ...
PMID:Overfeeding-induced ovarian dysfunction in broiler breeder hens is associated with lipotoxicity. 1649 48

Common features of polycystic ovary syndrome (PCOS), including hyperandrogenism, ovarian dysfunction and obesity, can be highly distressing. We compared 40 women with PCOS to women with infertility but not PCOS, and to women with neither PCOS nor infertility, on measures of depression and body image. Women with PCOS reported higher depression scores and greater body dissatisfaction (p < .001) than comparison group women. Body image was strongly associated with depression overall, even after controlling body mass. Among women with PCOS, body dissatisfaction measures and education explained 66 percent of the variance in depression, suggesting explanations of the PCOS-depression link should consider the role of potentially mediating psychosocial variables.
 ...
PMID:Depression and body image among women with polycystic ovary syndrome. 1676 40

Adiponectin, the most abundantly synthesized protein in adipose tissue, has plieotropic effects on liver, muscle, endothelium, placenta, and other tissues. We examined direct effects of recombinant porcine adiponectin on porcine ovarian granulosa cells in vitro. We demonstrate that adiponectin, at physiologically relevant levels (10-25 microg/ml), provokes expression of genes associated with periovulatory remodeling of the ovarian follicle over a time frame of 6-24 h. These include cyclooxygenase-2, prostaglandin E synthase, and vascular endothelial growth factor. Adiponectin modulates steroid synthetic protein gene expression, increasing steroidogenic acute regulatory protein transcript abundance and reducing cytochrome P450aromatase. Adiponectin has antidiabetic properties and sensitizes tissues to insulin. We show that it interacts with both LH and insulin in inducing expression of cyclooxygenase-2 transcripts in granulosa cells. We determined that the MAPK pathway, via phosphorylation of ERK1/2, is involved in mediation of the adiponectin signal in ovarian granulosa cells, rather than protein kinase A or the classic adiponectin transducer, AMP-activated protein kinase. Adiponectin synthesis is reduced in obesity, and our findings suggest that this reduction plays a role in obesity-related ovarian dysfunction.
 ...
PMID:Adiponectin induces periovulatory changes in ovarian follicular cells. 1691 53

The insulin resistance syndrome, also referred to as the metabolic syndrome or syndrome X, is associated with a primary cellular defect in insulin action (insulin resistance) and a compensatory increase in insulin secretion. The combination of insulin resistance and subsequent hyperinsulinaemia causes a number of metabolic and cardiovascular changes that result in a syndrome typically characterised by type 2 diabetes, obesity, dyslipidaemia, coronary artery disease and hypertension. Moreover, disturbances in sleep (sleep apnoea) and ovarian dysfunction are also characterised by insulin resistance. The pathophysiological basis for these disturbances reflects the impact of variable genetic and environmental influences. At a molecular level, insulin resistance involves defects of insulin signalling such as reduced insulin receptor tyrosine kinase activity and reduced post-receptor phosphorylation steps that impinge on metabolic and vascular effects of insulin.
 ...
PMID:The insulin resistance syndrome: physiological considerations. 1746 39

Polycystic ovary syndrome (PCOS) is the most common endocrine cause of hirsutism, acne, and pattern alopecia. It is a heterogeneous syndrome of hyperandrogenic anovulation that is typically due to intrinsic ovarian dysfunction, which is often aggravated by insulin-resistant hyperinsulinemia with its risks of diabetes mellitus and metabolic syndrome and their complications. Because there are many pitfalls to androgen assays, evaluation for hyperandrogenemia is suggested in women with moderate or severe hirsutism or hirsutism equivalents, menstrual irregularity, acanthosis nigricans, or intractable obesity. An endocrinologic work-up is necessary to rule out other hyperandrogenic disorders that require specific therapy (e.g., virilizing tumors, nonclassic congenital adrenal hyperplasia, hyperprolactinemia, and Cushing's syndrome). Ultrasonography helps in the differential diagnosis and may demonstrate the polycystic ovaries that have recently been vetted as an alternative to oligo-anovulation as a diagnostic criterion. Management of PCOS is determined by symptomatology. For those women not desiring pregnancy, the most common therapies are oral contraceptive pills, antiandrogens (contraindicated in the absence of adequate contraception), and insulin-lowering treatments (which have little effect on hirsutism).
 ...
PMID:What every physician should know about polycystic ovary syndrome. 1884 13

Hirsutism represents a primary clinical indicator of androgen excess. The most common endocrine condition causing hirsutism is polycystic ovary syndrome (PCOS). Diagnosing PCOS is not easy as the signs and symptoms are heterogenous. The newest diagnostic guideline made by the Androgen Excess and PCOS Society in 2006, claims the presence of hyperandrogenism, and ovarian dysfunction (oligo / anovulation and / or polycystic ovaries). Obesity associated reproductive and metabolic dysfunctions may aggravate the symptoms of PCOS. PCOS might be underdiagnosed in non obese women because lean PCOS phenotypes might be underestimated for the syndrome. Effective medical treatment of PCOS and associated hirsutism depends on the endocrinological expertise and experience of the therapist in each individual case. An algorithm for the treatment has not been established yet.
 ...
PMID:Endocrinology of hirsutism. 2118 21


<< Previous 1 2 3 4 5 Next >>