Leptin mRNA Expression In Adipose Tissue Research Articles

Elafin inhibits obesity, hyperglycemia, and liver steatosis in high-fat diet-treated male mice

Elafin is an antimicrobial and anti-inflammatory protein. We hypothesize that elafin expression correlates with diabetes. Among non-diabetic and prediabetic groups, men have significantly higher serum elafin levels than women. Men with type 2 diabetes mellitus (T2DM) have significantly lower serum elafin levels than men without T2DM. Serum elafin levels are inversely correlated with fasting blood glucose and hemoglobin A1c levels in men with T2DM, but not women with T2DM. Lentiviral elafin overexpression inhibited obesity, hyperglycemia, and liver steatosis in high-fat diet (HFD)-treated male mice. Elafin-overexpressing HFD-treated male mice had increased serum leptin levels, and serum exosomal miR181b-5p and miR219-5p expression. Transplantation of splenocytes and serum exosomes from elafin-overexpressing HFD-treated donor mice reduced food consumption and fat mass, and increased adipose tissue leptin mRNA expression in HFD-treated recipient mice. Elafin improved leptin sensitivity via reduced interferon-gamma expression and induced adipose leptin expression via increased miR181b-5p and miR219-5p expression. Subcutaneous and oral administration of modified elafin inhibited obesity, hyperglycemia, and liver steatosis in the HFD-treated mice. Circulating elafin levels are associated with hyperglycemia in men with T2DM. Elafin, via immune-derived miRNAs and cytokine, activates leptin sensitivity and expression that subsequently inhibit food consumption, obesity, hyperglycemia, and liver steatosis in HFD-treated male mice.

Maternal prolactin inhibition causes changes in leptin at 22- and 30-day-old pups.

Breastfeeding is associated with obesity prevention. We showed previously that prolactin inhibition at the end of lactation causes hyperleptinemia at weaning (PN21) and programs for obesity, insulin resistance, dyslipidemia, and leptin resistance (PN180). Here, we evaluate the source of neonatal hyperleptinemia and how it develops during the nutritional transition from milk through solid food. Lactating rats were treated with bromocriptine (BRO), a prolactin inhibitor, 0.5 mg twice a day, or saline (CON) for the last 3 days of lactation. All parameters were studied at PN22 and PN30. At PN22, BRO-treated rats showed lower food intake, body mass, and body length. At PN30, only body length and mesenteric fat mass were lower. Despite normal plasma leptin levels at PN22, the adipose tissue leptin mRNA expression was lower, while plasma leptin was higher in PN30, possibly due to a higher adipose mesenteric tissue production. At PN22, the hypothalamus seems to be more sensitive to leptin, since OBR and STAT3 are higher. Conversely, at PN30 leptin signaling pathway is suggestive of leptin resistance with lower STAT3 and higher SOCS3 in hypothalamus and consequently higher NPY. Glycemia was lower at PN22 and higher at PN30, without changes in plasma insulin levels. At PN30, BRO-treated rats had other metabolic changes such as higher plasma cholesterol, lower HDL-c, higher hepatic cholesterol and AST, suggesting a liver dysfunction. Our data show that milk supply can exert a crucial role in the imprinting of a second leptin peak, which is important for survival adaptation to adverse nutritional conditions.

Regulation of dietary energy level and oil source on leptin and its long form receptor mRNA expression of the adipose tissues in growing pigs

Two experiments were conducted to evaluate the effects of dietary energy level and source of oil on leptin mRNA and long form leptin receptor (Ob-Rl) mRNA expression in dorsal, abdominal and visceral adipose tissues in young growing pigs. In experiment one, 15 barrows (initial body weight 15.0 kg) were used to examine the effects of dietary energy levels on leptin mRNA and Ob-Rl mRNA expression. The pigs were randomly allotted to one of three dietary treatments ( n = 5 per treatment) containing 13.4, 15.1 or 16.7 MJ DE/kg diet for 28 days. Based on the results of experiment one, experiment two was designed to examine the effects of oil sources including soybean oil (rich in n-6 polyunsaturated fatty acids) or fish oil (rich in n-3 polyunsaturated fatty acids) on leptin mRNA and Ob-Rl mRNA expression in the same adipose tissues examined in experiment one. The energy content of these diets was 15.1 MJ/kg. Fourteen barrows (initial weight 20.5 kg) were allocated to either of the two dietary treatments ( n = 7 per treatment), which was supplemented with either soybean or fish oil (both 5.73% of the diet) and fed to the pigs for 21 days. At the end of both experiments, blood samples were collected to determine plasma leptin and insulin concentrations. Adipose tissues were sampled to determine leptin and Ob-Rl mRNA expression using real-time fluorescence quantification PCR. In experiment one, plasma leptin concentrations were enhanced ( P = 0.02), and insulin concentrations were decreased ( P < 0.01) in pigs fed the high-energy diet (16.7 MJ DE/kg). Dorsal adipose tissue leptin mRNA expression was increased by feeding the diet containing 15.1 MJ/kg DE compared with the diets containing 13.4 and 16.7 MJ/kg DE. There was no difference in leptin mRNA expression in abdominal and visceral adipose tissue. In experiment two, there were no differences in plasma leptin and insulin concentrations between pigs fed with either fish oil or soybean oil diets. Nevertheless, fish oil decreased both leptin mRNA and Ob-Rl mRNA expression in dorsal adipose tissues compared with soybean oil ( P < 0.01). These experiments indicate that the source of oil plays a more potent role in regulation of leptin mRNA expression relative to dietary energy levels by an insulin-independent mechanism. Plasma leptin concentrations may also be regulated by a post-transcriptional mechanism.

158 Materno-Fetal Transfer of 125-I-Leptin in The Dual in vitro Perfused Placenta Perfusion Model and Increased Leptin Mrna-Expression in Adipose Tissue of Pregnant Women

Background: Leptin is a growth factor for the fetus. The sources for maternal and fetal leptin plasma levels are the adipose tissue and the placenta. Placental leptin release elevates maternal leptin levels only about 15%. We hypothesize that activated adipose tissue is an additional source for the high leptin levels in pregnancy. However it is further not clear if maternal leptin reaches the fetal circulation and supports fetal growth by that way. Aim of the study: (1) Do maternal leptin arrive the fetal circulation and (2) is maternal adipose tissue leptin production activated during pregnancy ?Methods: Placentas and adipose tissue was obtained after written informed consent of the patients. (1) Dual in vitro perfusion of isolated cotyledons (n=7) for 3h. Addition of 125-I-leptin and unlabeled leptin (1+3, 22 ng/ml total leptin) to the maternal circulation. Control of vitality and integrity by measurement of glucose consumption, lactate production, creatinine- and antipyrin transfer. (2) Sampling of subcutaneous maternal adipose tissue during cesarean sections (n=10, no gestational pathology) and during other gynecological surgery (n=10, age matched, no malignancies). Measurement of leptin mRNA using Taqman real time PCR.Results: (1) Materno-fetal transfer rate of the labeled leptin was 4,5 ± 1,4% of the initial concentration. Permeability of 125-I-leptin accounted for 0,04 ± 0,02 ml min-1 g-1, and was 1,3 ± 0,1 ml min-1 g-1 normalized to creatinine transfer. Existence of free 125-iodine was excluded by comparison of dialysated and undialysated fetal perfusion medium. (2) Leptin mRNA was significant higher in adipose tissue of pregnant women than in the control group (1,0 ± 0,5 v. 0,5 ± 0,4 rel. Units; p<0,05)Conclusion: (1) We could show first, that leptin from the maternal circulation passes the placenta and enters the fetal blood. There seems to be an active transplacental transport from the maternal to the fetal circulation, due to molecular weight and calculated permeability. (2) Maternal adipose tissue leptin production is activated during pregnancy. A basic leptin supply in the beginning of fetal development seems to be guaranteed by the placenta and maternal adipose tissue and was supplemented by the own leptin production of the fetus during further maturation and growth.

Effects of estrous cycle and steroid replacement on the expression of leptin and uncoupling proteins in adipose tissue in the rat

Among other actions ,leptin has been suggested to increase energy expenditure and to modulate the menstrual cycle. In fact ,the main effect of leptin seems to be modulating the sympathetic nervous system and gonadotropin-releasing hormone pulsatility. We investigated whether changes in the plasma steroid concentrations during the estrous cycle and after ovariectomy and steroid replacement can modulate plasma leptin levels ,adipose tissue leptin mRNA expression ,and some of the candidates for mediating energy expenditure (uncoupling proteins (UCP) 1 ,2 ,and 3 mRNA) in white and brown adipose tissue. Rats in estrous cycle or ovariectomized rats with or without estradiol or progesterone replacement therapy for 18 days were studied. Plasma leptin ,insulin ,estradiol and progesterone were measured with radio-immunoassays. Leptin mRNA expression was measured in subcutaneous ,periovarian and mesenteric white adipose tissue and in interscapular brown adipose tissue. Expression of UCP 1 ,2 ,and 3 mRNA in periovarian white and brown adipose tissue was analyzed. Plasma leptin levels were significantly decreased in the estrous (1.1 ± 0.4 ng/ml) compared with the pro-estrous (1.7 ± 0.4 ng/ml ,F = 3.0 ,p = 0.046) phase of cycle. UCP1 mRNA levels in brown adipose tissue were more elevated during pro-estrus than during metestrus (F = 3.17 ,p = 0.039). Gene expressions of leptin ,UCP2 or UCP3 mRNA did not change significantly during the cycle. In ovariectomized rats ,estradiol and/or progesterone treatment had no effect on plasma leptin levels. Gene expression analysis of leptin and UCP1 ,2 and 3 in adipose tissue was not affected by steroid replacement. In conclusion ,the estrous cycle appears to have a minor effect on modulation of leptin and uncoupling proteins. Only plasma leptin levels and expression of UCP1 mRNA are modestly elevated during the estrous cycle in the rat. Since estrogen and/or progesterone substitution in ovariectomized rats does not affect circulating leptin concentration or expression of leptin and UCPs in adipose tissue ,it is unlikely that steroids play a major role in their regulation.

Effects of estrous cycle and steroid replacement on the expression of leptin and uncoupling proteins in adipose tissue in the rat

Among other actions ,leptin has been suggested to increase energy expenditure and to modulate the menstrual cycle. In fact ,the main effect of leptin seems to be modulating the sympathetic nervous systemand gonadotropin-releasing hormone pulsatility. We investigated whether changes in the plasma steroid concentrations during the estrous cycle and after ovariectomy and steroid replacement can modulate plasmaleptin levels ,adipose tissue leptin mRNA expression ,and some of the candidates for mediating energy expenditure (uncoupling proteins (UCP) 1 ,2 ,and 3 mRNA) in white and brown adipose tissue.Ratsin estrous cycle or ovariectomized rats with or without estradiol or progesterone replacement therapy for 18 days were studied. Plasma leptin ,insulin ,estradiol and progesterone were measured with radio-immunoassays.Leptin mRNA expression was measured in subcutaneous ,periovarian and mesenteric white adipose tissue and in interscapular brown adipose tissue. Expression of UCP 1 ,2 ,and 3 mRNA in periovarian white andbrown adipose tissue was analyzed. Plasma leptin levels were significantly decreased in the estrous (1.1 ± 0.4 ng/ml) compared with the pro-estrous (1.7 ± 0.4 ng/ml ,F = 3.0 ,p = 0.046)phase of cycle. UCP1 mRNA levels in brown adipose tissue were more elevated during pro-estrus than during metestrus (F = 3.17 ,p = 0.039). Gene expressions of leptin ,UCP2 or UCP3 mRNA did not changesignificantly during the cycle. In ovariectomized rats ,estradiol and/or progesterone treatment had no effect on plasma leptin levels. Gene expression analysis of leptin and UCP1 ,2 and 3 in adipose tissuewas not affected by steroid replacement.In conclusion ,the estrous cycle appears to have a minor effect on modulation of leptin and uncoupling proteins. Only plasma leptin levels and expression ofUCP1 mRNA are modestly elevated during the estrous cycle in the rat. Since estrogen and/or progesterone substitution in ovariectomized rats does not affect circulating leptin concentration or expressionof leptin and UCPs in adipose tissue ,it is unlikely that steroids play a major role in their regulation.

Leptin and tumor growth in rats.

We have examined the role of leptin in tumor-induced anorexia in 2 different tumor models. In rats bearing the Yoshida AH-130 ascites hepatoma, the reduction in food intake becomes important from day 6 after tumor inoculation. Interestingly, at day 4, when the animals do not show any anorectic behavior, circulating leptin levels were already reduced. Indeed, in all the tumor-bearing groups studied the levels of leptin were lower than in control animals. Moreover, the changes in the circulating levels paralleled changes in adipose tissue leptin mRNA expression, even at early stages following tumor inoculation when neither food intake nor fat stores were modified by the presence of a tumor. Interestingly, 7-day pair-fed controls showed changes similar to those present in tumor-bearing rats. These results agree with previous observations relating fasting to decreased leptin expression. Similar results were observed in another tumor model, the mouse Lewis lung carcinoma; i.e., at day 8 after tumor inoculation (when the animals did not show anorexia) both the circulating levels and the adipose leptin mRNA expression were also reduced. Our results suggest that experimental cancer-induced anorexia is not related to leptin changes.