Leptin In Group Research Articles

Does gastric tissue Ghrelin and Leptin correlate with serum values? A pilot study of the Indian Obese population

BackgroundWhile serum Ghrelin and leptin has been studied over the last decades, there are very few human studies correlating the serum levels with the presence of the ghrelin and leptin cells in gastric tissue. MethodsWe have assessed the presence of leptin and ghrelin cells in the resected sleeve of stomach following Laparoscopic Sleeve Gastrectomy (LSG) and correlated the same with serum levels of ghrelin and leptin hormones before and after 6 months of surgery. The study was conducted at department of gastro-intestinal (GI) surgery of a tertiary care hospital from 2017–2019. ResultsForty-five patients participated in the study. Thirty-five of the specimens were negative for ghrelin cells and 29 were negative for leptin cells. While the levels of serum ghrelin in the ghrelin-negative specimen group were lower than normal, the levels in the ghrelin-positive specimen group were significantly higher, which reduced following LSG. In the leptin group, while the leptin-positive group had higher serum levels that dropped after surgery, the leptin-negative group also showed raised serum leptin levels, which further increased after surgery. Serum ghrelin levels showed a positive correlation with serum insulin levels but did not translate to statistically significant increased number of diabetic patients. ConclusionGhrelin and leptin cells are not universally present in the stomach in Indian population. Serum values of leptin and ghrelin correlates positively to the presence of their secreting cells in the Gastric sleeve. This study gives scope to evaluate the presence and distribution of these cells in the gastric sleeve.

Effects of Profortil® on Leptin-Induced Adverse Effects on Sperm Parameters in Sprague-Dawley Rats

Raised leptin levels induce oxidative stress, which negatively impacts male reproduction. Profortil® is an antioxidant formulation clinically used to improve sperm quality. Whether Profortil® supplementation can prevent the detrimental effects of leptin on spermatozoa is not known. Thus, the aim of this study was to examine the effects of Profortil® on leptin-induced adverse effects on rat spermatozoa. Adult Sprague-Dawley rats were given either normal saline (control), leptin (60 µg/kg/day), Profortil® (50 mg/kg/day), or Profortil® + leptin once daily for 2 weeks. Sperm count and abnormal morphology were recorded. Testicular levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), superoxide dismutase (SOD), and catalase (CAT) activities were measured. TUNEL and Comet assays were performed. The sperm count in the Profortil® + leptin group was comparable to that in controls but was significantly higher than that in the leptin group, which was significantly lower than that in controls. Sperm morphology was not different between leptin and Profortil® + leptin groups. 8-OHdG level was significantly lower in the Profortil® + leptin group than that in the leptin group but was comparable to that in controls. CAT activity was not different between leptin and Profortil® + leptin groups, although activity in the former was significantly lower than that in controls. SOD activity was not different between groups. The apoptotic index was significantly higher in the leptin and Profortil® + leptin groups than in the control and Profortil® groups. Sperm DNA fragmentation was not significantly different between leptin and Profortil® + leptin groups. In conclusion, Profortil®, when given at 50 mg/kg/day for 3 weeks, was only able to reduce some, but not all the adverse effects of leptin on sperm parameters.

The Potential Role of Leptin in the Regulation of Maternal Weight during Pregnancy and Its Impact on Neonate Weight and Apgar

Leptin is secreted by adipose tissue and expressed in several organs, including the placenta. We investigated the influence of leptin in maternal blood on leptin expression and concentration in the placenta and umbilical cord and its influence on fetal weight and conditions at the time of birth. Twenty-five parturients were recruited, and after childbirth, placental tissue fragments, umbilical arteries, and vein blood were collected. According to leptin concentration in maternal peripheral blood, parturients were divided into low and high leptin groups. Mothers in the high-leptin group had higher age, pre-pregnancy weight, pre-pregnancy BMI, and weight in late pregnancy than mothers in the low-leptin group. Children of mothers in the high-leptin group presented an Apgar score modestly lower than those of the low-leptin group. No differences were observed in leptin concentrations in the umbilical artery and vein. However, the leptin retained in the fetus increased in the high-leptin group compared to the low-leptin group. We observed a negative correlation between fetal leptin retained and maternal age in the low-leptin group. In the high-leptin group, placental leptin concentration was positively correlated with maternal weight in late pregnancy. Nonetheless, the expression of the leptin receptor (Ob-Rb) was negatively correlated with newborn length. In conclusion, this study found a positive correlation between maternal leptin levels and maternal pre-pregnancy weight, BMI, and fetal birth weight. These findings suggest a potential role of leptin in maternal weight regulation during pregnancy and fetal growth.

Leptin Mediates Prostate Stromal Cell Proliferation, Smooth Muscle Contraction, and Mitochondrial Function in Benign Prostate Hyperplasia.

Leptin is a metabolic peptide hormone produced by adipocytes, with proven roles in proliferation of prostate cancer cells and of prostate cells in animal models of benign prostatic hyperplasia (BPH). Thus, the role of leptin as a molecular link connecting BPH and lower urinary tract symptoms (LUTS) suggestive of BPH with metabolic symptoms appears feasible but is still unknown. In fact, a connection between metabolic syndrome and BPH is becoming increasingly evident from epidemiologic studies. Key factors of Lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH/LUTS) are increased prostate smooth muscle tone, and prostate enlargement. Here, we examined the effects of leptin on contraction of human prostate smooth muscle and on growth of stromal cells. We performed microarray analysis to identify genes (fold change ≥ 1.5) associated with BPH/LUTS progression, such as those involved in proliferation, apoptosis, and mitochondrial metabolism, in rat prostate tissue (data from GSE129561). We then used electric field stimulation (EFS) to induce frequency-dependent, neurogenic contractions of human prostate strips, which were enhanced by leptin. We also examined the effect of leptin on human prostate stromal cells (WPMY-1) and found increased cell proliferation and viability upon exposure. To explore the underlying mechanism, we conducted mitochondrial stress assay using near-infrared (NIR) fluorescent dye and flow cytometry (FACS) analysis and observed reduced cellular apoptosis and preserved mitochondrial membrane potential (∆ψM) after leptin treatment. Microarray analysis reveals that leptin regulates prostate smooth muscle contraction and stromal cell proliferation, shedding new light on its involvement in BPH/LUTS pathogenesis and mitochondrial function. We found that leptin enhanced the proliferation rate of prostate stromal cells relative to the control group (0.67 ± 0.05 vs 0.54 ± 0.08, p-value= 0.024). Moreover, leptin (100 ng/mL) potentiated the frequency-dependent, neurogenic contractions of prostate strips elicited by EFS (p= 0.047 between leptin and control group). We also show that leptin treatment increased the mitochondrial membrane potential of prostate stromal cells and inhibited mitochondrial apoptosis. Our results indicate that leptin stimulates the contractility and proliferation of smooth muscle and stromal cells in the human prostate, implying a potential role for leptin in exacerbating BPH/LUTS in obese men. Leptin modulation may be a beneficial therapeutic strategy for patients with metabolic syndrome and BPH/LUTS. Further studies are warranted to elucidate the mechanisms and implications of the leptin system in BPH/LUTS.

Leptin as predictor of cardiovascular events and high platelet reactivity in patients undergoing percutaneous coronary intervention

Leptin is a hormone involved in the regulation of food intake. Previous studies suggested an interplay between leptin, platelet aggregation, and cardiovascular outcome but this issue was not investigated invivo in patients treated with percutaneous coronary intervention (PCI). We designed a study to evaluate the possible relation between leptin, cardiovascular outcome, and platelet reactivity (PR) in patients undergoing PCI. 155 PCI patients had preprocedural measurements of PR and leptin plasma levels. The latter were assessed by ELISA. Hyperleptinemia was defined as leptin levels ≥14ng/ml. PR was evaluated by the VerifyNowP2Y12 assay and expressed as P2Y12 reaction units (PRU). Patients were divided into three groups based on PR values and defined as low (LPR), normal (NPR), and high (HPR). Patients were followed for up 8 years. The primary endpoint was the incidence of Major Acute Cardiac Events (MACE) at long-term follow-up according to leptin groups. Secondary endpoints were the evaluation of leptin levels according to PR groups and the incidence of periprocedural myocardial infarction (PMI) according to leptin groups. Long-term follow-up was completed in 140 patients. Patients with hyperleptinemia experienced a higher MACE rate than the normoleptinemic group (HR 2.3; CI 95% 1.14-4.6, P=0.02). These results remained unchanged after adjusting for Body Mass Index, hypertension, and gender. Leptin levels were significantly different among groups of PR (P=0.047). Leptin levels were higher in the HPR group (12.61±16.58ng/ml) compared to the LPR group (7.83±8.87ng/ml, P=0.044) and NPR group (7.04±7.03ng/ml, P=0.01). The rate of PMI was higher in hyperleptinemia patients (15.1% vs. 6.5%, P=0.22). This study suggests that high leptin levels are associated with a worse clinical outcome in patients undergoing PCI and with HPR. Further studies are needed to define better the pathophysiological pathways underlying this association.

Leptin and melatonin's effects on OVX rodents' bone metabolism.

This study aims to examine the effects of leptin and melatonin intervention on bone metabolism in ovariectomize (OVX) rodents, as well as their potential mechanisms of action. Prepare an OVX model of osteoporosis in rodents and validate the model by collecting bilateral tibia samples for Micro-CT scanning and histological analysis. A control group of normal size, the OVX group, the OVX+Sema4D (Semaphorin 4D) group, the OVX+Sema4D+Leptin group, the OVX+Sema4D+ Melatonin(MT) group and the OVX+Sema4D+Leptin+ MT group were the experimental groups. Adenovirus vector construction and tibial medullary injection validation were conducted in accordance with the aforementioned experimental groups. Four groups of rats were injected with the Sema4D overexpression adenovirus vector into the tibial medullary cavity, and two groups were injected with the Leptin overexpression adenovirus vector. The repair of osteoporosis was observed using micro-CT and histological analysis. Immunohistochemical detection of bone morphogenetic protein-2 (BMP-2) expression in bone tissue was employed to ascertain the amount of osteoclasts in the upper tibial metaphysis, utilizing TRAP(tartrate-resistant acid phosphatase) staining. Increased levels of BV/TV, Tb.N, BMD, and BMC were seen in the OVX+ Sema4D+Leptin, OVX+ Sema4D+MT, and OVX+ Sema4D+Leptin+ MT groups compared to the OVX group, whereas Tb. Sp levels were lowered. When compared to the Sema4D overexpression group, the trabecular bone structure of the OVX + Sema4D + Leptin, OVX + Sema4D + MT, and OVX + Sema4D + Leptin + MT groups is largely intact, tends to be closer, and the amount of trabecular bone increases. The OVX + Sema4D + Leptin + MT group in particular.The expression of BMP-2 was dramatically upregulated (p<0.05), the number of TRAP-stained osteoclasts was significantly reduced (p<0.05), and BALP(bone-derived alkaline phosphatase) and TRAP-5b(tartrate-resistant acid phosphatase-5b) activities were significantly downregulated (p<0.05). In rats with osteoporosis, leptin and melatonin can be seen to augment the trabecular microstructure of the bone, augment bone growth, diminish trabecular harm, and mend the bone. The combined effect is more powerful.

Changes in Lipid Metabolism Enzymes in Rat Epididymal Fat after Chronic Central Leptin Infusion Are Related to Alterations in Inflammation and Insulin Signaling.

Leptin inhibits food intake and reduces the size of body fat depots, changing adipocyte sensitivity to insulin to restrain lipid accrual. This adipokine may modulate the production of cytokines that could diminish insulin sensitivity, particularly in visceral adipose tissue. To explore this possibility, we examined the effects of chronic central administration of leptin on the expression of key markers of lipid metabolism and its possible relationship with changes in inflammatory- and insulin-signaling pathways in epididymal adipose tissue. Circulating non-esterified fatty acids and pro- and anti-inflammatory cytokines were also measured. Fifteen male rats were divided into control (C), leptin (L, icv, 12 μg/day for 14 days), and pair-fed (PF) groups. We found a decrease in the activity of glucose-6-phosphate dehydrogenase and malic enzyme in the L group, with no changes in the expression of lipogenic enzymes. A reduction in the expression of lipoprotein lipase and carnitine palmitoyl-transferase-1A, together with a decrease in the phosphorylation of insulin-signaling targets and a low-grade inflammatory pattern, were detected in the epididymal fat of L rats. In conclusion, the decrease in insulin sensitivity and increased pro-inflammatory environment could regulate lipid metabolism, reducing epididymal fat stores in response to central leptin infusion.

Association between sedentary time and plasma leptin levels in middle-aged and older adult population in Taiwan: A community-based, cross-sectional study.

Association of sedentary behavior and plasma leptin levels is a popular topic in recent research. Aged populations often suffer from cardiometabolic diseases, and leptin is considered a novel marker for many cardiometabolic diseases. To further explore this topic, our research investigates the relationship between sedentary time and serum leptin levels in middle-aged and older populations. A total of 396 middle-aged and older adult Taiwanese participants were included in this study. We recorded their self-reported sitting time as sedentary time. Participants were categorized into low leptin, medium leptin group, and high leptin groups according to the tertile of serum leptin level in the study. We also analyzed the anthropometric and cardiometabolic parameters between the three groups. Spearman's correlation coefficient was used to analyze the correlation between leptin level, sedentary time, and other cardiometabolic risk factors. The relationsip between leptin and sedentary time was also shown in a scatter plot. Multivariate linear regression was performed to determine the association between serum leptin levels and sedentary time after adjusting for age, sex, alcohol consumption, smoking, triglycerides, body mass index (BMI), fasting plasma glucose, systolic blood pressure, uric acid, creatinine, and alanine transaminase (ALT). In our study, data from a total of 396 participants were analyzed. The average age of participants was 64.75 (±8.75) years, and ~41.4% were male. A longer period of sedentary time was observed in the high leptin group. A positive correlation was found between serum leptin level and sedentary time in Spearman's correlation, in all BMI groups. Serum leptin levels were positively associated with sedentary time (B = 0.603, p = 0.016) in the multivariate linear regression after adjusting for age, sex, alcohol consumption, smoking, triglycerides, BMI, fasting plasma glucose, systolic blood pressure, uric acid, creatinine, and ALT. Prolonged sedentary time can be an independent risk factor for high serum leptin levels, and high leptin levels can be a novel marker in future healthcare to screen the individual with prolonged sedentary time. Furthermore, based on our study, future research can further explore the relationship between leptin levels and health promotion, especially decreasing sedentary time in the middle-aged and elder population, which is vulnerable to cardiometabolic diseases.

Leptin alleviated ovarian ischemia-reperfusion injury in rats via modulation of Sirt-1/Nrf2 and TLR4/NF-kB/caspase-3 signaling pathways.

Objective. Ovarian torsion is a gynecological emergency that occurs mostly during the female reproductive years due to ovarian masses or surgical manipulation. This work aims to explore the probable protective effect of leptin on rat ovaries due to ischemia-reperfusion (IR) injury. Methods. Wistar albino rats were divided into four groups: 1) control group; 2) ovarian IR group (OVIR); 3) leptin group I [OVIR + leptin (10 µg/kg body weight, b.w.)]; and 4) leptin group II (OVIR + leptin (100 µg/kg b.w.)]. Serum levels of estradiol and anti-Mullerian hormone (AMH) were measured. Levels of oxidative stress and inflammatory markers in ovarian tissue were determined along with the expression of sirtuin 1 (Sirt1), nuclear erythroid factor-2 (Nrf2), cyclooxygenase-2 (COX-2), nuclear factor kappa (NF-κB), toll like receptor-4 (TLR4), and caspase-3. Results. Serum estradiol and AMH levels were decreased with increased expression of COX-2, TLR4, caspase-3, and NF-κB and decreased expression of Sirt1and Nrf2 in ovary of the OVIR group, which were improved by exogenous administration of both leptin doses. Conclusion. Leptin administration dose-dependently reduced the severity of OVIR injury via modulation of Sirt-1/Nrf2 and TLR4/NF-kB/caspase-3 signaling pathways. Thus, leptin may be used as an adjuvant measure to prevent ovarian damage and improve the outcomes. However, clinical studies are needed to evaluate these results in humans.

Relationships of body composition and adipocytokines with outcomes in metastatic castration-resistant prostate cancer patients receiving docetaxel chemotherapy.

We evaluated the relationships of body composition and serum adipocytokine levels with progression-free survival (PFS) and overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients receiving docetaxel. The medical records of mCRPC patients who received docetaxel between January 2011 and December 2015 at Fudan University Shanghai Cancer Center (Shanghai, China) were reviewed. The following body composition parameters were calculated using computed tomography: skeletal muscle index (SMI), visceral adipose tissue index (VATI), and subcutaneous adipose tissue index (SATI). Pretreatment serum adipocytokine levels, including interleukin 6, insulin, leptin, monocyte chemoattractant protein-1, adiponectin, and resistin, were measured using the multiplex bead-based immunoassays. Cox regression and Kaplan-Meier methods were used for survival analyses. Of the 453 mCRPC patients initially identified, 105 were included in the analysis. High VATI group patients had longer PFS (median, 10 months vs 7 months, P = 0.008) and OS (median, 24 months vs 15 months, P = 0.017), compared with low VATI group patients. SMI and SATI were not significantly associated with PFS or OS. Of the six detected adipocytokines, only leptin was associated with mCRPC prognosis. High leptin group patients had shorter PFS (median, 7 months vs 12 months, P = 0.0018) and OS (median, 17 months vs 22 months, P = 0.042), compared with low leptin group patients. Multivariate analysis showed that a high VATI was an independent protective factor for PFS and OS, while a high leptin level was an independent risk factor for PFS and OS. Therefore, VATI and serum leptin levels could provide important information concerning mCRPC prognosis.

Elevated serum leptin levels are associated with lower renal function among middle-aged and elderly adults in Taiwan, a community-based, cross-sectional study.

Plasma leptin is considered a risk factor for obesity and cardio-metabolic disease, but the link between serum leptin and renal function is still under evaluation. In our study, we focused on the relationship between serum leptin and renal function, and we investigated the relationship in more detail. The 396 middle-aged and elderly Taiwanese adults recruited for our health survey were the subject of our research. All participants agreed to participate and signed a consent form before they joined and completed our study. We divided the participants into three groups according to eGFR tertiles and analyzed the parameters between each group. Then, we used Pearson's correlation test to investigate the relationship between eGFR levels and cardio-metabolic risk factors with adjustment for age. The scatter plot indicates the trend between serum leptin levels and eGFR levels. Participants were reclassified into three subgroups according to their leptin levels and the bar chart reveals the prevalence of chronic kidney disease (CKD) in each group. Finally, we used multivariate linear regression to evaluate the relationship between serum leptin and eGFR levels with adjustment for age, sex, smoking status, drinking status, body mass index (BMI), uric acid levels, hypertension (HTN), diabetes mellitus (DM), and dyslipidemia. In our study, we analyzed the data from 396 eligible participants. A total of 41.4% of the participants were male, and the average age of all participants was 64.81 years ( ± 8.78). The participants in the high eGFR group were more likely to have lower serum leptin levels. Furthermore, eGFR values were negatively correlated with serum leptin levels even after adjustment for age. The prevalence of CKD in the high serum leptin group was higher than that in the low serum leptin group. Serum leptin levels showed significant negative correlations with eGFR levels (β=-0.14, p<0.01) in the multivariate linear regression after adjusting for age, sex, smoking status, drinking status, BMI, uric acid levels, HTN, DM, and dyslipidemia. According to our study, serum leptin levels show a negative relationship with eGFR levels in middle-aged and elderly people in Taiwan. In addition, high serum leptin levels could be an novel marker to survey kidney failure in clinical practices.

Association of higher plasma leptin levels with HOMA-IR index, high sensitivity C-reactive protein and glycolipid metabolism in patients with chronic schizophrenia: A multi-center cross-sectional study.

BackgroundPrevious research has revealed that plasma leptin levels were closely related to glycolipid metabolism in schizophrenic patients. Insulin resistance (IR) and high sensitivity C-reactive protein (hs-CRP) were involved in glucolipid metabolism disorders. This study explored the correlation between plasma higher leptin levels, homeostasis model assessment of insulin resistance (HOMA-IR) index, hs-CRP and glycolipid metabolism in patients with chronic schizophrenia (CS).Methods322 subjects were enrolled, and the psychopathological symptoms of each patient were assessed by a 30-item Positive and Negative Syndrome Scale (PANSS−30). Patients' plasma leptin levels were measured by enzyme-linked immunosorbent assay (ELISA). Fasting blood glucose (FBG) levels were determined by oxidase method. Insulin levels were tested by electrochemiluminescence, and hs-CRP levels were tested by immunoturbidimetry. IBM SPSS 22.0 was used for data analysis.ResultsCompared to the lower leptin group, patients in the higher leptin group had significantly higher body mass index (BMI), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL-C), insulin, HOMA-IR and hs-CRP levels; and lower negative factor scores, cognitive factor scores, and PANSS total scores (P < 0.05). Plasma leptin levels in CS patients were positively correlated with BMI, TC, TG, LDL-C, insulin, HOMA-IR and hs-CRP levels, and were negatively correlated with gender (male = 1, Female = 2), positive factor scores, negative factor scores, cognitive factor scores and PANSS total scores. Multiple linear regression analysis revealed that gender, BMI, positive factor scores, PANSS total scores, FBG, LDL-C, insulin, HOMA-IR and hs-CRP levels were independent influencing factors of leptin levels in CS patients (P < 0.05).ConclusionGender, BMI, positive factor scores, PANSS total scores, FBG, LDL-C, insulin, HOMA-IR and hs-CRP levels were independent influencing factors of plasma leptin levels in CS patients. Plasma leptin, HOMA-IR and hs-CRP levels should be measured regularly in CS patients to prevent or treat the disorders of glucose and lipid metabolism comorbidity with schizophrenia patients in clinical diagnosis and treatment.

Local administration of low doses of exogenous BMP2 and leptin promotes ectopic bone regeneration in leptin-deficient mice.

Obesity and leptin deficiency are associated with compromised bone regeneration. This study aims to investigate the role of locally administrated low-dose BMP2+leptin on bone regeneration in leptin-deficient obese (ob/ob) mice. Wildtype (WT) and ob/ob mice were divided into 3 groups (4mice/group): BMP2 (5μg) group, BMP2+low-dose leptin (1μg) group, and BMP2+high-dose leptin (2.5μg) group. WT mice were used as control mice. An equal size absorbable collagen sponge was prepared by loading the BMP2 or/and leptin and implanted subcutaneously. After 19 days, samples were collected and analyzed by micro-CT and H&E staining. No significant difference in bone regeneration among the three groups in WT mice. Quantification of newly formed bone parameters from micro-CT and H&E staining showed that low-dose BMP2 treatment formed less new bone in ob/ob mice compared to WT. BMP2+low-dose leptin treatment substantially rescued the compromised bone regeneration in ob/ob mice up to the level in WT mice. However, the BMP2 and high dose of leptin failed to rescue the compromised bone regeneration in ob/ob mice. Our findings suggest that a combination of the low-dose BMP2 and leptin could be a strategy to promote osteogenesis in obese populations with leptin deficiency.

Influence of In Ovo Leptin Injection into Yolk Sac on Embryo Development, Blood Biochemical Parameters and Lipid Metabolism of Broiler Chicks during Early Post-Hatching Period

The study aimed to investigate the effect of in ovo (IO) leptin injection on yolk sac leptin concentration, embryo development, blood lipid metabolism, and biochemical parameters of broiler chicks during the early post-hatching period. Hatching eggs were weighed and placed in an incubator with 100 eggs/4 replications/group. The groups were: non-injected group (C); and 3 injected groups with 100 μl of phosphate buffer solution (PBS); 0.5 μl leptin (L0.5), and 1 μl leptin (L1) in 100 μl of PBS. Pure leptin hormone dissolved in PBS was injected into the yolk sac on day 7 of incubation. Yolk/yolk sac leptin concentrations at the onset of incubation, on days 7 and 15 of incubation, and at hatching were determined. Embryo/chick development was determined at all ages. Serum leptin, tri-iodothyronine (T3), thyroxine (T4), creatine kinase, total protein, uric acid, and lipid profiles were measured at hatching and day 7 of chick age. The leptin level of the yolk was similar to the leptin level of the yolk sac at hatching. Leptin level of a yolk sac was higher on 7th day than at other ages. IO injection* age was significant for serum leptin level, which was similar to one-day chicks in the L0.5 at day 7 of chick age. T3, T4, creatine kinase, uric acid, lipid profiles, and embryo/chick development did not change with IO leptin. Serum HDL level was higher in the leptin groups than C and PBS groups at hatching. IO leptin application affects blood lipid metabolism depending on dose level for male broiler chicks at the early post-hatch period, without affecting embryo/chick development.Leptin level of yolk was similar to leptin level of yolk sac at hatching. Leptin level of yolk sac was higher on 7th day than other ages. IO injection* age was significant for serum leptin level, which was similar to one-day chicks in the L0.5 at day 7 of chick age. T3, T4, creatine kinase, uric acid, lipid profiles, and embryo/chick development did not change with IO leptin. Serum HDL level was higher in the leptin groups than C and PBS groups at hatching. IO leptin application affects blood lipid metabolism depending on dose level for male broiler chicks at early post-hatch period, without affecting embryo/chick development.

Leptin Enhances Nitric Oxide Production and Decreases Blood Flow in Rat Skeletal Muscle

Objective: There are a few studies related to nitric oxide (NO) and leptin interaction in the regulation of physiological events in skeletal muscle. Therefore, the aim of the present study is to investigate the interaction of leptin and NO in response to blood flow and nitric oxide synthase (NOS) distribution on rat skeletal muscle. Materials and Methods: Twenty-four adult-male Wistar albino rats were divided into 4 groups: control (C), Leptin (LP) (50 μg/kg), L-NG-nitroarginine methyl ester (LN) (a non-specific nitric oxide synthase inhibitor, 10 mg/kg,) and L-NAME+Leptin (LN+LP) administrated groups. Drugs were administered via the right jugular vein. Hemodynamic parameters: mean arterial pressure, heart rate and blood flow were recorded during the experiment and at the end blood samples for biochemical analyses of leptin and nitrite/nitrate levels and gastrocnemius muscle tissues from the right hindlimb for NOS distribution were taken. Results: Leptin infusion after L-NAME administration significantly decreased heart rate and blood flow (p&lt;0.05, p&lt;0.001). In addition, there was no change in the mean arterial pressure in the leptin group and leptin-administered L-NAME group. Leptin levels were the highest in the LP+LN group (p&lt;0.01). Decreased nitrate/nitrate levels with L-NAME administration (p&lt;0.01 vs C) reached control values by leptin infusion. Both endothelial NOS (eNOS) and neuronal NOS (nNOS) distributions were observed in the skeletal muscle cells of the leptin group. Conclusion: Although NO synthesis is inhibited by L-NAME, it is concluded that leptin partially enhances NO production and leptin uses NO as a mediator in its physiological effects.

Effects of leptin on proliferation and differentiation of hypoxic rat retinal progenitor cells in vitro

To investigate the the effects of leptin on the proliferation, differentiation and PTEN expression of rat retinal progenitor cells (RPCs) cultured under hypoxic condition. SD rat RPCs were cultured in normoxic conditions or exposed to hypoxia in the presence of 0, 0.3, 1.0, 3.0, 10, and 30 nmol/L leptin for 12, 48 and 72 h, and the cell viability was assessed using cell counting kit 8 (CCK 8) assay. The RPCs in primary culture were divided into control group, hypoxia group, and hypoxia+leptin group, and after 48 h of culture, the cell medium was replaced with differentiation medium and the cells were further cultured for 6 days. Immunofluorescence staining was employed to detect the cells positive for β-tubulin III and GFAP, and Western blotting was used to examine the expression of PTEN at 48 h of cell culture. The first generation of RPCs showed suspended growth in the medium with abundant and bright cellular plasma and formed mulberry like cell spheres after 2 days of culture. Treatment with low-dose leptin (below 3.0 nmol/L) for 48 h obviously improved the viability of RPCs cultured in hypoxia, while at high concentrations (above 10 nmol/L), leptin significantly suppressed the cell viability (P < 0.05). The cells treated with 3.0 nmol/L leptin for 48 h showed the highest viability (P < 0.05). After treatment with 3.0 nmol/L leptin for 48 h, the cells with hypoxic exposure showed similar GFAP and β-tubulin Ⅲ positivity with the control cells (P>0.05), but exhibited an obvious down-regulation of PTEN protein expression compared with the control cells (P < 0.05). In rat RPCs with hypoxic exposure, treatment with low dose leptin can promote the cell proliferation and suppress cellular PTEN protein expression without causing significant effects on cell differentiation.

Leptin improves in-vitro maturation of goat oocytes through MAPK and JAK2/STAT3 pathways and affects gene expression of cumulus cells

We investigated whether the recombinant leptin (1, 10, 100 ng/mL) influences the meiotic maturation of goat oocytes, whether the MAPK and JAK2/STAT3 pathways mediate the effects of leptin during in-vitro maturation, and whether leptin differently affects the abundance of mRNAs relevant to leptin signal transduction and apoptosis in oocytes and cumulus cells. The addition of leptin to the maturation medium positively affected the number of oocytes that completed nuclear maturation. Nuclear oocyte maturation stimulated by leptin was significantly impaired when we added the specific inhibitors of MAPK (U0126) and JAK2/STAT3 (AG490) to the maturation medium. The addition of leptin (10 ng/mL) during maturation did not affect the expression of AMPKα1, PPARα, Caspase 3, and BCL2 genes in oocytes or cumulus cells. The PPARγ and BAX mRNA abundances were significantly reduced in cumulus cells in the leptin group compared to the control group. Our results demonstrate that supplementation of the in-vitro maturation medium with leptin significantly improves nuclear maturation and reveal the important role of the MAPK and JAK2/STAT3 signaling pathways in establishing the leptin-mediated nuclear maturation of goat oocytes. Moreover, leptin treatment affects PPARγ and BAX gene expression in cumulus cells.

Evaluating the correlation of serum leptin levels with evidence of coronary artery disease on myocardial perfusion single-photon emission computed tomography in suspected coronary artery disease patients.

Cardiovascular disease is currently the most common cause of death worldwide. Several risk factors have been identified for cardiovascular diseases, including hypertension, hyperlipidemia and diabetes. Leptin is a peptide hormone that acts as a proinflammatory cytokine and has a variety of effects in hemostasis and metabolism such as lipid metabolism, production of glucocorticoid, angiogenesis, etc. The aim of this study was to determine the relationship between the concentrations of leptin with evidence of coronary artery disease in the myocardial perfusion scan. A one year retrospective cross-sectional study was conducted on patients who are suspected of coronary artery disease that referred to the nuclear medicine department for performing myocardial perfusion scan. The patients were classified based on the results of the myocardial perfusion scan. Serum leptin was measured with ELISA assay. The correlation of serum leptin with these parameters and also with different groups of age, sex and coronary artery disease risk factors was also compared. The mean serum level of leptin was 290.44 ng/ml (82.9-1600 ng/ml). There is no meaningful relation between serum leptin and coronary artery disease risk factors, age and sex; also, none of the quantitative myocardial perfusion scan parameters have a significant correlation with serum leptin. Based on our findings, there was no significant correlation between myocardial perfusion scan parameters and leptin levels. Serum leptin and different groups of age, sex and coronary artery risk factors were not correlated as well.

Effects of Aerobic Exercise on Rats with Hyperandrogenic Polycystic Ovarian Syndrome.

Hyperandrogenism is a key pathologic characteristic of polycystic ovarian syndrome (PCOS), and exercise can alleviate the accompanying inflammation and decrease the high androgen levels, but the mechanism is still unclear, so the purpose of this study is to explore the pathophysiologic characteristics of hyperandrogenic PCOS and the mechanism underlying its amelioration with aerobic exercise. Thirty-two female rats were randomly allocated to a normal control group (NC, n = 8), exercise control group (EC, n = 8), PCOS group (PC, n = 8), and PCOS plus exercise group (PE, n = 8). The PC and PE groups were injected with a dehydroepiandrosterone (DHEA) solution to induce the hyperandrogenic PCOS rat model. The EC and PE groups underwent a Masashi swimming protocol (120 min per session, 6 days/week, for 15 days). Results indicated that the concentrations of leptin (LP) in the EC group were significantly lower than those in the NC group (p < 0.05). Compared with the NC group, the levels of testosterone (T), estradiol (E2), follicle-stimulating hormone (FSH), LP, anti-Müllerian hormone (AMH), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and free fatty acids (FFA) were all significantly augmented in the PC group (all p < 0.05). In addition, compared with the NC group, the levels of adiponectin (ADP) were significantly decreased (p < 0.05), and the expression of aromatase cytochrome P450 (P450arom) in ovarian tissue was significantly elevated in the PC group (p < 0.05). The levels of T, FSH, LP, and FFA were also significantly increased in the PE group (p < 0.05). Compared with the PC group, the levels of T and LP in the PE group were significantly diminished (p < 0.05), and the levels of ADP were significantly increased in the PE group (p < 0.05). T was positively correlated with E2, FSH, AMH, LP, TNF-α, IL-6, and FFA levels, while ADP was negatively correlated with LP and E2. These results showed that hyperandrogenism, chronic low-grade inflammation, and leptin resistance may interact to influence the occurrence and development of PCOS. Aerobic exercise can alleviate the internal inflammation by relieving leptin resistance and may mitigate the sex hormone disorder and hyperandrogenism in rats with PCOS by affecting the hypothalamic-pituitary-ovarian axis.

The Role of Obesity in the Development of Kidney and Glomerular Ultrafiltration Barrier Injuries: Leptin Contributions

Introduction Obesity is associated with multiple risk factors to the development of comorbidities such as kidney injuries. Lesions in the glomerular ultrafiltration barrier may cause impairment of the kidney filtration process. Nephrin is one of the main components of the glomerular ultrafiltration barrier, so changes in the expression of this protein indicate impaired renal function. Thus, the aim of this study is to investigate the role of obesity in the development of kidney and glomerular ultrafiltration barrier injuries. The contribution of leptin to kidney function in this context was also evaluated. Methods The protocols are in agreement with CEUA (nº 13/2017). Twenty-four mice aged 18 weeks were used: Six C57BL / 6J were assigned to the lean control group (CTL) and 18 ob/ob (provided by Prof. Dr. José Donato Junior from ICB-USP) were randomly assigned to obese control group (ob/ob) and obese treated with leptin group (ob/ob - lep). Leptin treatment was performed through osmotic mini-pump (model 1004, Alzet) insertion. Mini-pumps were filled with a solution containing leptin at a dose of 3.5 μg/day for 42 days. During the treatment period food intake was monitored daily. Weight gain and blood glucose were monitored weekly. At the end of the treatment period, the animals were kept in metabolic cages for 24 hours to evaluate water intake and urine collection. Ultimately, the animals were submitted to euthanasia by exsanguination. Renal function was assessed by plasma concentration of creatinine and urea, and urinary albumin excretion. Renal tissue was used to evaluate gene expression by qPCR, histological and immunofluorescence analysis. Results Plasma leptin measurements confirm that ob/ob animals did not produce leptin and that introduction of exogenous leptin elevated the levels of this hormone to values close to control. Ob/ob - lep group had a reduction in food intake and body weight when compared to ob/ob group, this reduction led to values of food intake and body weight similar to CTL group. There were no changes in water intake, urine flow and blood glucose among groups. There were also no changes in plasma creatinine values among groups, however, in the ob/ob group, there was an increase in serum urea and leptin treatment partially reversed this parameter to values closer to CTL. In ob/ob animals, there was an increase in urinary albumin excretion and leptin treatment lowered this parameter to values closer to CTL group. Inflammation of the renal tissue in obese animals was confirmed by increased IL-6 mRNA expression, leptin had no effect at this parameter. There was no significant difference in the expression of mRNA to MCP1 between groups. However, there is a tendency to increasing that gene's expression in obese animals and leptin treatment reduces that parameter back to control. In 42 days of protocol, there was no glomerular hypertrophy in the ob/ob group, however, there was a reduction in the expression of nephrin and leptin treatment did not reverse this parameter. Conclusion: Obesity impairs renal function, increases expression of inflammatory molecules and decreases nephrin expression. Leptin therapy was partially renoprotective since it reversed some of the observed parameters.