Ob mRNA In Adipose Tissue Research Articles

Expression of Leptin (Ob Gene Product) in Reproductive System with Special Reference to Polycystic Ovary Syndrome

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. 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 non-PCOS, 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.Keywords: Ob mRNA, Serum leptin, body mass index, body fat distribution, infertility, ovary.

Swimming training down-regulates plasma leptin levels, but not adipose tissue ob mRNA expression

The aim of the present study was to assess the effects of endurance training on leptin levels and adipose tissue gene expression and their association with insulin, body composition and energy intake. Male Wistar rats were randomly divided into two groups: trained (N = 18) and sedentary controls (N = 20). The trained group underwent swimming training for 9 weeks. Leptin and insulin levels, adiposity and leptin gene expression in epididymal and inguinal adipose tissue were determined after training. There were no differences in energy intake between groups. Trained rats had a decreased final body weight (-10%), relative and total body fat (-36 and -55%, respectively) and insulin levels (-55%) compared with controls (P < 0.05). Although trained animals showed 56% lower leptin levels (2.58 +/- 1.05 vs 5.89 +/- 2.89 ng/mL in control; P < 0.05), no difference in leptin gene expression in either fat depot was demonstrable between groups. Stepwise multiple regression analysis showed that lower leptin levels in trained rats were due primarily to their lower body fat mass. After adjustment for total body fat, leptin levels were still 20% (P < 0.05) lower in exercised rats. In conclusion, nine weeks of swimming training did not affect leptin gene expression, but did lead to a decrease in leptin levels that was independent of changes in body fat.

The Obesity in Bilateral Ovariectomized Rats Is Related to a Decrease in the Expression of Leptin Receptors in the Brain

We investigated the expression levels of leptin receptors in the brain of ovariectomized (OVX) rats. The mean expression level of ob mRNA in adipose tissues of OVX rats was significantly ( P < 0.01) lower than that in the SHAM operation group rats, and the mean body weight of OVX rats was significantly ( P < 0.01) greater than that in the SHAM group rats. However, there were no differences between serum leptin concentrations in these two groups. The mean level of leptin receptor (OB-R) mRNA expression in the brain tissue and the mean level of long form type OB-R (OB-RL) mRNA expression in the hypothalamus of the OVX rats were significantly ( P < 0.05) lower than those in the SHAM group rats. These changes were cancelled by supplementation with 17 β-estradiol in OVX rats. These results suggested that not only changes in the expression level of ob mRNA in adipose tissue and the serum leptin concentration but also changes in the OB-R mRNA in the brain are involved in the body weight increase in OVX rats and that a decrease in OB-R makes transmission of signals to suppress the amount of food intake difficult, thus leading to an increase in body weight.

Adipose tissue ob mRNA expression in humans: discordance with plasma leptin and relationship with adipose TNFα expression

Elevated plasma leptin levels are found in obese humans, suggesting a defect in the function of leptin in regulating body weight and adiposity. In 53 subjects covering a broad range of adiposity, we examined the relationships between plasma leptin, adipose tissue ob mRNA levels, and adipose tissue TNF mRNA. There was a highly significant correlation between plasma leptin levels and every index of adiposity. In contrast, the relationship between ob mRNA levels and adiposity was weak. Adipose tissue from obese subjects demonstrated higher ob mRNA levels than adipose tissue from lean subjects (lean: 0.49 ± 0.05; obese 0.87 ± 0.09 arbitrary units, P < 0.05). However, there was no significant correlation between body fat and ob mRNA level. In addition, there was no significant relationship between ob mRNA levels and plasma leptin levels, which were measured in the same subjects. In addition to the measure of ob mRNA levels, adipose TNF mRNA levels were measured in 18 subjects. TNF mRNA levels varied with ob mRNA levels (r = 0.44, P = 0.06). These data show that plasma leptin levels are not directly related to adipose tissue ob mRNA levels, suggesting posttranscriptional regulation of leptin expression, either at the level of the adipocyte, or by alteration of plasma leptin degradation or clearance. In addition, the parallel changes in ob and TNF mRNA in adipose tissue suggest that these two important factors in the defense against obesity may be regulated similarly.—Ranganathan, S., M. Maffei, and P. A. Kern. Adipose tissue ob mRNA expression in humans: discordance with plasma leptin and relationship with adipose TNFα expression. J. Lipid Res. 1998. 39: 724–730.

Invited Editorial on “Acute and chronic effects of exercise on leptin levels in humans”

the discovery of the ob gene only a little over 2 yr ago provided new insight into the mechanisms through which body weight and composition are regulated ([14][1]). Simply put, leptin, the product of the ob gene, is a hormone that communicates to the brain the amount of adipose tissue in the body.

Plasma leptin concentrations and OB gene expression in subcutaneous adipose tissue are not regulated acutely by physiological hyperinsulinaemia in lean and obese humans.

To determine the effects of obesity on fasting plasma leptin levels and assess the effects of feeding on plasma leptin and OB gene expression in subcutaneous adipose tissue in non-diabetic subjects. Blood and subcutaneous adipose tissue needle biopsy samples were obtained after an overnight fast and 1, 2 and 3 h following a mixed meal (606 kcal). Eighteen female subjects: eight lean with a mean age of 40.1 yr (range 20-65) and mean body mass index of 22.24 kg/m2 (range 18.6-26.6) and ten obese subjects with a mean age of 48.6 yr (range 29-71) and body mass index of 33.53 kg/m2 (range 28.7-41.7). Apart from obesity the only significant difference between groups was a 2.6 fold higher fasting plasma leptin concentration in obese subjects compared to leans (26.9 +/- 2.9 vs 10.2 +/- 2.22 (P < 0.05) respectively). Adipose tissue OB mRNA levels were not significantly higher in the obese group. Plasma leptin correlated with BMI and visceral fat weight in lean subjects only. No significant association between plasma leptin and adiposity was evident in obese patients. In addition, there was no association between plasma leptin and the insulin: glucose ratio (an index of insulin sensitivity). Following a mixed meal, post-prandial plasma insulin levels were significantly increased, with a concomitant significant reduction in plasma NEFA levels in both groups. Despite the large increase in plasma insulin, there were no post-prandial changes in either plasma leptin concentrations or subcutaneous adipose tissue OB mRNA levels in either lean or obese subjects. The data indicate that plasma leptin levels are correlated with the degree of adiposity, especially in lean subjects, and confirm that circulating leptin levels are greater in obese subjects than lean subjects. The present study also failed to show a significant association between plasma leptin and insulin sensitivity in lean and obese women. Furthermore, plasma leptin and subcutaneous adipose tissue OB gene expression are not under short term regulation following feeding in fasted lean or obese female subjects.

Obese gene expression: reduction by fasting and stimulation by insulin and glucose in lean mice, and persistent elevation in acquired (diet-induced) and genetic (yellow agouti) obesity.

Mutations in the obese (ob) gene lead to obesity. This gene has been recently cloned, but the factors regulating its expression have not been elucidated. To address the regulation of the ob gene with regard to body weight and nutritional factors, Northern blot analysis was used to assess ob mRNA in adipose tissue from mice [lean, obese due to diet, or genetically (yellow agouti) obese] under different nutritional conditions. ob mRNA was elevated in both forms of obesity, compared to lean controls, correlated with elevations in plasma insulin and body weight, but not plasma glucose. In lean C57BL/6J mice, but not in mice with diet-induced obesity, ob mRNA decreased after a 48-hr fast. Similarly, in lean C57BL/6J controls, but not in obese yellow mice, i.p. glucose injection significantly increased ob mRNA. For up to 30 min after glucose injection, ob mRNA in lean mice significantly correlated with plasma glucose, but not with plasma insulin. In a separate study with only lean mice, ob mRNA was inhibited >90% by fasting, and elevated approximately 2-fold 30 min after i.p. injection of either glucose or insulin. These results suggest that in lean animals glucose and insulin enhance ob gene expression. In contrast to our results in lean mice, in obese animals ob mRNA is elevated and relatively insensitive to nutritional state, possibly due to chronic exposure to elevated plasma insulin and/or glucose.

Intracerebroventricular administration of neuropeptide Y to normal rats increases obese gene expression in white adipose tissue

The aim of this work was to determine the possible inter-relationship between neuropeptide Y (NPY, a hypothalamic stimulator of feeding) and adipose tissue expression of the ob protein (a novel potent inhibitor of feeding). Such a relationship could be of importance in the maintenance of normal body weight. To this end, normal rats were intracerebroventricularly (i.c.v.) infused for 6 days with NPY. NPY infusion resulted in hyperphagia and a marked increase in adipose tissue ob mRNA levels. The effect of NPY on ob expression persisted when hyperphagia was prevented by pair-feeding, and was reversed following cessation of NPY infusion. Basal and glucose-stimulated insulinaemia were increased by i.c.v. NPY infusion compared to control values, regardless of whether animals were ad libitum-fed or pair-fed. Cessation of NPY infusion was accompanied by normalisation of insulinaemia. These changes in insulinaemia produced by i.c.v. NPY infusion paralleled the observed changes in ob expression. When normal rats were made hyperinsulinaemic-euglycaemic for 24 h, such hyperinsulinaemia also resulted in increased ob mRNA levels in white adipose tissue. This suggested that NPY-induced hyperinsulinaemia could be responsible for the upregulation of ob mRNA levels of NPY-infused rats. It is concluded that central (i.c.v.) NPY infusion increases adipose tissue ob expression, a functional relationship that is linked, at least in part, via NPY-induced hyperinsulinaemia.

The ob gene and insulin. A relationship leading to clues to the understanding of obesity.

Obesity and non-insulin-dependent diabetes are estimated to affect millions of people in the world. This pathology is multifactorial, comprising complex interactions of genetic and environmental factors and lacking a specific therapy. Great interest arose from the recent discovery of the ob gene expressed only in adipose tissue and coding for a protein that appears to regulate adiposity, potentially by acting as a satiety factor. We report here that in normal rats, ob mRNA is respectively up- or downregulated by a rise in insulinemia (induced by 2-day insulin infusion while maintaining euglycemia) or a decrease in insulinemia (induced by a 3-day fast). Our results also show that in genetically obese fa/fa rats studied longitudinally, white adipose tissue ob mRNA levels increase in parallel with early occurring and steadily increasing hyperinsulinemia. This results in adult obese animals having markedly higher ob mRNA levels than age-matched normoinsulinemic lean rats. Furthermore, in adult obese rats, ob mRNA escapes down-regulation as normalization of hyperinsulinemia due to fasting fails to reduce the high ob mRNA levels.