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International Journal of Health Research
Abstract and Figures
Abstract
Purpose: To determine serum leptin and its ob mRNA
expression both in the PCOS and non-PCOS ovary,
endometrium and adipose tissue in normal or polycystic ovary
syndrome (PCOS) in South Indian population.
Methods: The regulation of ob gene expression in thin,
overweight, obese and morbidly obese PCOS (Polycystic
Ovary Syndrome) and non-PCOS subject’s endometrium,
ovary and adipose tissue were investigated using a reverse
transcription-competitive polymerase chain reaction method to
quantify the mRNA levels of leptin and compared with normal
weight control adipose tissue.
Results: Endometrium, ovary and adipose tissue ob mRNA
levels were highly correlated with serum leptin, BMI and body
fat distribution of 80 subjects (10 normal weight, 8 thin PCOS,
8 thin non-PCOS, 7 overweight PCOS, 7 overweight nonPCOS, 10 obese PCOS, 10 obese non-PCOS, 10 morbidly
obese PCOS and 10 morbidly obese non-PCOS). Ob mRNA
levels were positively correlated with serum levels of
dehydroepiandrosterone sulphate, free testosterone, luteinizing
hormone, and prolactin. Ob mRNA level was inversely
correlated with SHBG and androstenedione.
Conclusion: Here, we report for the first time in Indian
population, that endometrium, ovary, adipose tissue ob mRNA
levels and serum leptin are highly correlated and are different
in expression levels in thin, obese, morbidly obese PCOS and
non-PCOS, when compared to individuals with normal weight.
The leptin could be a novel, independent risk factor for PCOS.
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... It is most useful in controlling the involuntary functions such as gagging. 2 Journal of South Asian Association of Pediatric Dentistry, Volume 3 Issue 2 (July-December 2020) ...
... It is effective in bringing suggestions into the nervous system for the control of involuntary functions of the body. 2 Techniques used to reduce bias were • Crossover study was adopted so that the sequence effect would be diminished. • Children with age less than 6 years were excluded from the study, since the less developed cognition of the child would have created bias in the results of 5-point patient-reported scale. ...
Audiovisual translation (AVT) is the term used to refer to the transfer from one language to another of the verbal components contained in audiovisual works and products. Feature films, television programs, theatrical plays, musicals, opera, Web pages, and video games are just some examples of the vast array of audiovisual products available and that require translation. As the word suggests, audiovisuals are made to be both heard (audio) and seen (visual) simultaneously but they are primarily meant to be seen. We talk of “watching” a movie, a show, or even an opera; we “see” programs that are “shown” on television. However, while the verbal and visual codes in audiovisuals are linked to such an extent that the words naturally tend to rely heavily on the visuals, the translation of these products operates on a verbal level alone.
Aims
Obesity is associated with the increased prevalence of infertility and is also an independent risk factor in women with polycystic ovary syndrome (PCOS). The aim of this study was to examine the extent to which the ob gene product, leptin, alone or in combination with other metabolic and endocrinal parameters, may be correlated to infertility with the incidence of PCOS.
Methods
Serum leptin levels were measured in both PCOS and non-PCOS subjects of the following categories, such as thin, overweight, obese and morbidly obese, and compared with normal weight women. Female infertility is associated with body mass index, percentage of body fat, body fat distribution, and other biochemical and endocrinal parameters parameters.
Results
Women with PCOS and normally menstruating control women were analyzed by univariate analysis for body fat distribution. Serum leptin was positively correlated with body mass index, percentage of body fat, serum levels of dehydroepiandrosterone sulfate, testosterone, free testosterone, luteinizing hormone and prolactin. Serum leptin was inversely correlated with serum sex hormone-bi nding globulin concentration and androstenedione.
Conclusions
We report, for the first time in the Indian population, that leptin levels are different in thin and morbidly obese PCOS patients than in regularly menstruating normal weight subjects, and leptin could be a novel, independent risk factor for PCOS.
Genetic studies in mice have identified the ob gene product as a potential signaling factor regulating body weight homeostasis and energy balance. It is suggested that modulation of ob gene expression results in changes in body weight and food intake. Glucocorticoids are shown to have important metabolic effects and to modulate food intake and body weight. In order to test the hypothesis that these metabolic effects of glucocorticoids are linked to changes in the expression of the ob gene, ob mRNA levels were evaluated in rats treated with different glucocorticosteroids at catabolic doses and correlated to the kinetics of changes in body weight gain and food intake. Results from time course experiments demonstrate that adipose tissue ob gene expression is rapidly induced by glucocorticosteroids. This induction is followed by a concordant decrease in body weight gain and food consumption. These data suggest that the catabolic effects of corticosteroids on body weight mass and food intake might be mediated by changes in ob expression. Modulation of ob expression may therefore constitute a mechanism through which hormonal, pharmacological, or other factors control body weight homeostasis.
The sterility of male and female homozygous ob/ob mice is a recognized feature of the ob mutation (1). Whereas ob/ob males can occasionally reproduce if maintained on a restricted diet, ob/ob females are always sterile (2). Thinning of the ob/ob females to normal weight by diet-restriction failed to correct their sterility. Early sexual development is normal in ob/ob females; however, ovulation never follows and the mice remain prepuberal indefinitely with no occurrence of oestrus cycles. Reproductive hormones are reduced in ob/ob females (3) demonstrating a functional defect from the hypothalamic-pituitary axis (4-6). The ovaries of ob/ob females are capable of producing viable eggs when transplanted into lean female recipients (7). Reconstitution of reproductive functions in the ob/ob female necessitates delivery of hypothalamic extracts to the third ventricle (8) and administration of pituitary extract (9), gonadotropic hormones (10), progesterone (11) and relaxin (12). These previous findings demonstrate that the sterility of ob/ob females is caused by an insufficiency of hormones at the hypothalamic-pituitary level rather than physical hindrance of copulatory activity, pregnancy and parturition caused by excess adipose tissue. We show here that repeated administration of only the recombinant human ob protein, leptin, into homozygous female ob/ob mice can correct their sterility, thus resulting in ovulation, pregnancy and parturition.
The regulation of ob gene expression in abdominal subcutaneous adipose tissue was investigated using a reverse transcription-competitive PCR method to quantify the mRNA level of leptin. Leptin mRNA level was highly correlated with the body mass index of 26 subjects (12 lean, 7 non-insulin-dependent diabetic, and 7 obese patients). The effect of fasting on ob gene expression was investigated in 10 subjects maintained on a hypocaloric diet (1045 KJ/d) for 5 d. While their metabolic parameters significantly changed (decrease in insulinemia, glycemia, and resting metabolic rate and increase in plasma ketone bodies), the caloric restriction did not modify the leptin mRNA level in the adipose tissue. To verify whether insulin regulates ob gene expression, six lean subjects underwent a 3-h euglycemic hyperinsulinemic (846 +/- 138 pmol/liter) clamp. Leptin and Glut 4 mRNA levels were quantified in adipose tissue biopsies taken before and at the end of the clamp. Insulin infusion produced a significant threefold increase in Glut 4 mRNA while leptin mRNA was not affected. It is concluded that ob gene expression is not acutely regulated by insulin or by metabolic factors related to fasting in human abdominal subcutaneous adipose tissue.
The expression of leptin and its receptors was examined by reverse transcriptase-polymerase chain reaction and immunofluorescence in granulosa and cumulus cells of pre-ovulatory follicles and in meiotically mature oocytes obtained from women undergoing in-vitro fertilization. Leptin concentrations were measured in newly aspirated follicular fluids and in maternal serum before and after the administration of an ovulatory dose of human chorionic gonadotrophin. The findings demonstrate leptin expression at the mRNA and protein levels by granulosa and cumulus cells, and the presence of leptin in mature human oocytes. While an association between follicular leptin concentration and embryo development was not observed, a post-ovulatory increase in serum leptin concentration was associated with implantation potential. The results are discussed with respect to possible roles of leptin in early human development.
An important gene involved in the pathogenesis of obesity is the product of the human homologue of the murine obese gene (gene symbol OBS). Using fluorescence in situ hybridization (FISH), we have localized the human OB gene to human chromosome 7, specifically to region 7q32.1. The FISH data of human OBS provide a gene-associated marker for genetic mapping. 8 refs., 1 fig.
Recent findings suggested that alterations in insulin receptor isoform expression might be involved in the molecular mechanism of insulin resistance. Using reverse transcription reaction followed by competitive polymerase chain reaction, we measured the level of the receptor mRNA variants in rat insulin-sensitive tissues, under conditions of decreased insulin effectiveness (fasting, aging, and diabetes). The liver expressed the mRNA variant with exon 11 predominantly, and the hind limb skeletal muscles expressed the mRNA without exon 11. The heart and epididymal adipose tissue expressed both variants. Fasting and streptozocin-induced diabetes increased the level of receptor mRNAs in the liver but did not modify the repartition between the two variants. The modification of the expression ratio, in favor of the form with exon 11, found by some authors in the skeletal muscle of insulin-resistant patients was not observed in rat muscles that expressed > 99% of the form without exon 11 under all the conditions tested. In adipose tissue, the proportion of both mRNA variants was never altered (45% of exon 11-positive [Ex11+]), while the total receptor mRNA concentration changed markedly during fasting or aging. The only modification observed in the isoform distribution was a significant decrease in Ex11+ mRNA concentration in the liver, muscle, and heart of old rats. We conclude that alternative splicing of insulin receptor mRNA is not involved in the impairment of insulin action during fasting or diabetes. Its potential role in the insulin resistance of old animals remains to be defined.
Leptin, the product of the ob gene, is a hormone secreted by adipocytes. Animals with mutations in the ob gene are obese and lose weight when given leptin, but little is known about the physiologic actions of leptin in humans.
Using a newly developed radioimmunoassay, wer measured serum concentrations of leptin in 136 normal-weight subjects and 139 obese subjects (body-mass index, > or = 27.3 for men and > or = 27.8 for women; the body-mass index was defined as the weight in kilograms divided by the square of the height in meters). The measurements were repeated in seven obese subjects after weight loss and during maintenance of the lower weight. The ob messenger RNA (mRNA) content of adipocytes was determined in 27 normal-weight and 27 obese subjects.
The mean (+/- SD) serum leptin concentrations were 31.3 +/- 24.1 ng per milliliter in the obese subjects and 7.5 +/- 9.3 ng per milliliter in the normal-weight subjects (P < 0.001). There was a strong positive correlation between serum leptin concentrations and the percentage of body fat (r = 0.85, P < 0.001). The ob mRNA content of adipocytes was about twice as high in the obese subjects as in the normal-weight subjects (P < 0.001) and was correlated with the percentage of body fat (r = 0.68, P < 0.001) in the 54 subjects in whom it was measured. In the seven obese subjects studied after weight loss, both serum leptin concentrations and ob mRNA content of adipocytes declined, but these measures increased again during the maintenance of the lower weight.
Serum leptin concentrations are correlated with the percentage of body fat, suggesting that most obese persons are insensitive to endogenous leptin production.
Polycystic ovary syndrome (PCOS) is associated with chronic anovulation, hyperandrogenemia, insulin resistance (IR)/hyperinsulinemia, and a high incidence of obesity. Thus, PCOS serves as a useful model to assess the role of IR and chronic endogenous insulin excess on leptin levels. Thirty-three PCOS and 32 normally cycling (NC) women of similar body mass index (BMI) were studied. Insulin sensitivity (S(I)) was assessed by rapid ivGTT in a subset of 28 PCOS and 29 NC subjects; percent body fat was determined by dual-energy x-ray absorptiometry (DEXA) in 14 PCOS and 17 NC. Fasting (0800 h) and 24-h mean hourly insulin levels were 2-fold higher (P < 0.0001), and S(I) was 50% lower (P = 0.005) in PCOS than in NC, while serum androstenedione (A), testosterone (T), 17-alpha hydroxyprogesterone (17OHP), and estrone (E1) levels were elevated (P < 0.0001), and sex hormone-binding globulin (SHBG) levels were decreased (P < 0.01). Twenty-four hour LH pulse frequency, mean pulse amplitude, and mean LH levels were elevated in PCOS (P < 0.001) as compared with NC. Serum leptin levels for PCOS (24.1 +/- 2.6 ng/mL) did not differ from NC (21.5 +/- 3.5 ng/mL) and were positively correlated with BMI (r = 0.81) and percent body fat (r = 0.91) for the two groups (both P < 0.0001). Leptin levels for PCOS and NC correlated positively with fasting and 24-h mean insulin levels (r = 0.81, P < 0.0001 for both PCOS and NC) and negatively with S(I) and SHBG levels. Leptin concentrations for PCOS, but not NC, correlated positively with 24-h mean glucose levels and inversely with 24-h mean LH levels and 24-h mean LH pulse amplitude. Leptin levels were not correlated with estrogen or androgen levels for either PCOS or NC, although leptin levels were positively related to the ratios of E1/SHBG and E2/SHBG for both PCOS and NC and to the ratio of T/SHBG for PCOS only. In stepwise multivariate regression with forward selection, only 24-h mean insulin levels contributed significantly (P < 0.01) to leptin levels independent of BMI and percent body fat for both PCOS and NC. Given this relationship and the presence of 2-fold higher 24-h mean insulin levels in PCOS, the expected elevation of leptin levels in PCOS was not found. This paradox may be explained by the presence of adipocyte IR specific to PCOS, which may negate the stimulatory impact of hyperinsulinemia on leptin secretion, a proposition requiring further study.
The polycystic ovary syndrome (PCOS) is characterized by menstrual disturbances, chronic anovulation and hyperandrogenism and is associated with insulin resistance and hyperinsulinemia. Leptin, the product of the ob gene, is an adipocyte-secreted molecule that signals the magnitude of energy stores to the brain and has been recently shown to have important effects on the reproductive axis of rodents. To assess the potential contribution of leptin to the pathogenesis of PCOS, we measured leptin levels in 24 obese women with PCOS and 12 weight- and age-matched controls and determined whether alterations in hyperinsulinemia produced by administration of the insulin-sensitizing agent troglitazone had an effect on serum leptin levels. Leptin concentrations at baseline were not different in women with PCOS (38.1 +/- 2.15 ng/mL) and controls (33.12 +/- 2.39 ng/mL). Moreover, leptin concentrations remained unchanged after treatment with troglitazone (38.1 +/- 2.15 vs. 39.21 +/- 2.65 ng/mL). Baseline leptin correlated strongly with body mass index in both controls (r = 0.59; P < 0.05) and women with PCOS (r = 0.70; P = 0.0004). Leptin levels were not associated with baseline insulin, testosterone, non-sex hormone-binding globulin (SHBG)-bound testosterone, dehydroepiandrosterone sulfate, estradiol, or SHBG. Finally, despite significantly reduced insulin, non-SHBG-bound testosterone, and estradiol levels after troglitazone treatment of women with PCOS, their leptin levels remained unchanged. We conclude that circulating leptin levels in patients with PCOS do not differ from those in age- and weight-matched controls. Furthermore, increased circulating insulin due to insulin resistance does not appear to alter circulating leptin levels in women with PCOS.