Serum Leptin Concentrations Research Articles

ThTP2.4 Long-Term Changes in Leptin, Chemerin, and Ghrelin Levels Following Roux-en-Y Gastric Bypass and Laparoscopic Sleeve Gastrectomy

Abstract Aim Published reports showed conflicting results regarding the sustained alterations in leptin, chemerin, and ghrelin concentrations after metabolic surgery. Therefore, we performed the present work to contrast the alterations in leptin, chemerin, and ghrelin levels one year after Roux-en-Y gastric bypass (RYGB) versus laparoscopic sleeve gastrectomy (LSG). Methods The present research is a prospective, comparative one that followed 100 cases for whom RYGB or LSG was done. We assessed the serum values of adiposity-associated mediators, including adipokcytokines (leptin and active chemerin) and gastrointestinal hormones (total ghrelin). The primary outcome in the present study was the alterations in leptin, chemerin, and ghrelin values at 12 months after RYGB and LSG. Results The serum leptin level decreased significantly in the LSG group with a mean change of − 170.8 ± 29.4 ng/mL (p <0.001). Similarly, the serum leptin concentration decreased significantly in the RYGB group, with a mean change of − 165.42 ±53.4 (p < 0.001). In addition, the mean reduction in baseline chemerin levels 12 months after the operation was considerable in the LSG cohort (− 23.24 ± 9.5 ng/mL) and RYGB group (− 22.12 ± 15.9 ng/mL). The ghrelin values demonstrated a notable reduction in the LSG cohort (− 0.083 ± 0.11 pg/mL) and RYGB group (− 0.068 ± 0.097 pg/mL). However, the changes in the three hormones were not substantially different between both groups (p > 0.05). Conclusion Both RYGB and LSG result in a considerable, comparable decrease in the postoperative serum concentrations of leptin, chemerin, and ghrelin.

Adipocyte-Derived Adipokines and Other Obesity-Associated Molecules in Feline Mammary Cancer.

Obesity has been identified as a serious health concern in domestic cats. Feline mammary cancer (FMC) is also a concern, as it is highly prevalent and aggressive. Considering the identified connection between obesity and breast cancer, it is worthwhile to investigate the potential obesity-cancer relationship in FMC. This review investigated the association between adipokines and other obesity-associated molecules and FMC, with the aim of identifying gaps in the current literature for future research. Based on the reports to date, it was found that tissue concentrations of leptin, serum concentrations of leptin receptor, serum amyloid A, and estrogen correlate positively with FMC, and serum concentrations of leptin correlate negatively with FMC. The roles of adiponectin and prolactin in FMC development were also investigated, but the reports are either lacking or insufficient to suggest an association. Numerous research gaps were identified and could be used as opportunities for future research. These include the need for studies on additional cohorts to confirm the association of leptin/leptin receptor and serum amyloid A with FMC, and to address the role of adiponectin and prolactin in FMC. It is also important to investigate the genetic determinants of FMC, evaluate the use of molecular-targeted therapies in FMC, and exploit the enrichment of the triple-negative immunophenotype in FMC to address current clinical needs for both human triple-negative breast cancer and FMC. Finally, mechanistic studies with any of the molecules reviewed are scarce and are important to generate hypotheses and ultimately advance our knowledge and the outcome of FMC.

Effect of fermented rapeseed meal on growth performance, nutrient digestibility, and intestinal health in growing pigs

To explore the effects of fermented rapeseed meal (FRSM) on growth performance and intestinal health, a total of 30 growing pigs were randomly allotted to three treatments consisting of corn-soybean meal diet (CSD), rapeseed meal diet (RSD), and fermented rapeseed meal diet (FRSD). Results showed that compared with RSD, FRSD feeding increased the average daily gain and final body weight in pigs (P < 0.01). Compared with RSD feeding, FRSD feeding elevated the apparent digestibility of crude protein, acid detergent fiber, and ether extract in pigs (P < 0.01). Moreover, the FRSD group exhibited greater apparent ileal digestibility of His, Thr, Lys, and Ser than the RSD group (P < 0.01). The digestible energy, metabolic energy, and nitrogen utilization were higher in the FRSD and CSD groups than in the RSD group (P < 0.01). As compared to the RSD, FRSD feeding decreased the serum concentration of leptin but significantly increased the concentrations of immunoglobulin (Ig) A, IgG, ghrelin, and enzyme activities of amylase, lipase, and trypsin in the pancreas (P < 0.05). Interestingly, the villus height, the ratio of villus height to crypt depth, and the activities of brush border enzymes (e.g., maltase and sucrase) in the small intestine were higher in the CSD and FRSD groups than in the RSD group (P < 0.05). As compared to the RSD, the FRSD feeding not only increased the expression level of the occludin in the small intestinal epithelium (P < 0.05) but also elevated the expression levels of claudin-1, MUC1, and PepT1 genes in the duodenum, and elevated the expression levels of SGLT1 and CAT1 genes in the jejunum (P < 0.05). Importantly, FRSD feeding significantly decreased the abundance of Escherichia coli, but increased the abundance of Lactobacillus and the content of butyrate in the cecum and colon (P < 0.05). These results indicated that compared with rapeseed meal, fermented rapeseed meal exhibited a positive effect on improving the growth performance and intestinal health in growing pigs, and the results may also help develop novel protein sources for animal nutrition and the feed industry.

Association of Serum Leptin and Adiponectin Concentrations with Type 2 Diabetes Biomarkers and Complications Among Saudi Women.

Hyperglycemia and insulin resistance (IR) put obese women with Type 2 diabetes mellitus (T2DM)at risk for cardiovascular disease (CVD). 150 T2DM women aged 30-45 were studied cross-sectionally at Madinah Hospital lab to find T2DM risk factors and their association with adiponectin/leptin levels. Women with T2DM showed greater fasting blood glucose (FBG), hemoglobin A1c (HbA1c), triglycerides (TG), body mass index (BMI), waist circumference (WC), insulin resistance (IR), high-sensitivity C-reactive protein (hs-CRP), and CVD risk (high atherogenic index of plasma (AIP) and leptin), but decreased high-density lipoprotein (HDL-cholesterol) and poor insulin sensitivity with low adiponectin. Obese women with T2DM had increased leptin and reduced adiponectin. Leptin levels were significantly related to IR, BMI, and AIP (B= 3.97, P= 0.02) but not WC. Leptin levels were negatively correlated with insulin sensitivity (IS) and HDL-c (P<0.05). In linear regression analysis, adiponectin levels had a significant association with IS and HDL-c (P= 0.03, P= 0.04) but an inverse relationship with IR, BMI, WC (B=-2.91, P= 0.04), and AIP (P<0.05). Increased leptin levels are related to high IR, AIP, and BMI among T2DM female patients. Similarly, adiponectin levels decrease IS and HDL-c. Therefore, obese T2DM women with high leptin and low adiponectin levels should be periodically checked to avoid or decrease consequences like CVD.

Effects of Exogenous Glucocorticoid Infusion on Appetitic Center Development in Postnatal Dairy Bull Calves.

The objective of this study was to determine the effects of exogenous glucocorticoid administration on leptin concentrations and brain development markers, such as protein and hypothalamic gene expression, in dairy bull calves. Within 4 h of parturition, Holstein bulls were intravenously infused with either a low cortisol dose (LC; n = 9, 3.5 µg/kg of body weight (BW)), high cortisol dose (HC; n = 9, 7.0 µg/kg BW), or control (CON; n = 9, saline) dose, with a 2nd infusion 24 h postpartum. Jugular blood was collected prior to infusion and daily until the calves were euthanized (day 5). Cerebrospinal fluid (CSF) from the third ventricle and adipose (omental, perirenal, and mesenteric) and hypothalamic tissue were collected. The blood and CSF samples were analyzed for leptin concentrations. The data were analyzed using SAS. Serum (p = 0.013) and CSF (p = 0.005) leptin concentrations in HC- and LC-treated calves were decreased compared with CON-treated calves. Leptin protein expression was decreased (p < 0.044) in perirenal and omental adipose tissue of LC-treated calves compared with CON-treated calves. Gene abundance of brain-derived neurotrophic factor and fibroblast growth factors 1 and 2 were decreased (p < 0.006) in HC- and LC-treated calves compared with CON-treated calves. In summary, cortisol administered to dairy bull calves reduced leptin concentrations, decreased leptin protein expression in perirenal and omental adipose tissue, and altered gene expression in hypothalamic tissue.

Relationships of the size of abdominal and perirenal fat depots with markers of meta‑inflammatory and renal damage in patients with resistant hypertension

Objective. To study possible correlations between the quantitative characteristics of fat depots in the abdominal and perirenal regions according to magnetic resonance imaging (MRI) data with metabolic and immunoinflammatory parameters, renal function, blood pressure (BP), as well as anthropometric data in patients with resistant hypertension (RH).Design and methods. Sixty-three patients (26 men) with RH aged 60 [54; 64] years who were receiving individual treatment with antihypertensive medication (mean, 4,3 ± 1,1 drug per day) were included in the study. Systolic/diastolic/pulse BP (SBP/DBP/PBP) was 157,7 ± 15,4 / 86,3 ± 13,6 / 71,3 ± 14,5 mm Hg. Mean body mass index (BMI) 34,1 [31,0; 38,5] kg/m2, waist circumference (WC) 108 [102; 113] cm (95,2 % with abdominal obesity). Diabetes mellitus type 2 suffered 51,6 %, chronic kidney disease C3–30,6 %. Clinical and laboratory examinations were performed. Creatinine level with estimated glomerular filtration rate (CKD-EPI), biomarker levels were assessed by ELISA. MRI was performed in a high-field tomograph with a magnetic field induction on 1,5 T. Mean parameter values in apparently healthy volunteers were considered normal. The area of visceral adipose tissue (S VAT) and subcutaneous adipose tissue (S SAT) was determined at the L4-L5 level (normal 123,5 [101,0; 169,0] and 216,5 [167,0; 287,0] cm2, respectively); kidney diameter — the anterior-posterior size of the kidney at the level of the renal vein (normal 5,0 [4,4; 5,4] cm); the thickness of perirenal adipose tissue (PRAT) as the difference between the distance between the sheets of Gerota’s fascia at the level of the renal vein and the diameter of the kidney (normal 1,2 [0,9; 2,4] cm); thickness of anterior subcutaneous adipose tissue (SATT) at the level of the umbilicus (normal 2,7 [1,8; 3,8] cm), the ratio of PRAT/SATT (normal 0,72 ± 0,61).Results. An increase was observed in all fat depots: S VAT 271,2 ± 104,4 cm2, S SAT 309,5 [236,0; 400,0] cm2, PRAT 2,7 [1,8; 3,9] cm, SATT 3,0 [2,3; 3,7] cm. Anthropometric parameters were associated with S VAT and S SAT. The thickness of PRAT correlated only with weight (r = 0,44) and WC (r = 0,41), whereas SATT correlated with BMI (r = 0,49). The PRAT/SATT ratio was not dependent on BMI. S VAT was associated with the level of PBP (r = 0,30). The following associations were observed with metainflammatory markers: TNF-α with S VAT (r = 0,31) and S SAT (r = 0,43) and with BMI (r = 0,32) and WC (r = 0,38); hsCRP with S SAT (r = 0,30), PRAT thickness (r = 0,34), and SATT (r = 0,34); leptin level correlated only with subcutaneous adipose tissue (S SAT, r = 0,60 and SATT, r = 0,69) and BMI (r = 0,51). Kidney size was 5,5 [5,0; 6,0] cm and was not associated with BMI. A decrease in kidney size was associated with a decrease in estimated glomerular filtration rate (r = 0,36). Glomerular filtration rate was associated with PRAT, as was creatinine (r = 0,43), which was also correlated with S VAT (r = 0,32). No correlations were found between renal function and anthropometric data.Conclusions. In patients with RH, there is an increase in the size of fat depots in the abdominal and perirenal regions according to MRI, which are closely related to anthropometric parameters and markers of inflammation. A direct correlation between the serum concentration of leptin and the size of subcutaneous adipose tissue has been established. An increase in the ratio of PRAT/SATT indicates an increase in the predominantly visceral component of adipose tissue and is associated with an increase in PBP, which reflects vascular stiffness. The decrease in the filtration function of the kidneys is correlated with an increase in the size of perirenal fat depots in the absence of direct links with dimensions of subcutaneous adipose tissue and anthropometric characteristics.

Association between serum leptin concentrations and homeostasis model assessment-insulin resistance of 2.5 and higher in normal weight Japanese women

Normal weight insulin resistant phenotype was characterized in 251 Japanese female university students using homeostasis model assessment-insulin resistance. Birth weight, body composition at age 20, cardiometabolic traits and dietary intake were compared cross-sectionally between insulin sensitive (< 1.6, n = 194) and insulin resistant (2.5 and higher, n = 16) women. BMI averaged < 21 kg/m2 and waist < 72 cm and did not differ between two groups. The percentage of macrosomia and serum absolute and fat-mass corrected leptin concentrations were higher in insulin resistant women although there was no difference in birth weight, fat mass index, trunk/leg fat ratio and serum adiponectin. In addition, resting pulse rate, serum concentrations of free fatty acids, triglycerides and remnant-like particle cholesterol were higher in insulin resistant women although HDL cholesterol and blood pressure did not differ. In multivariate logistic regression analyses, serum leptin (odds ratio:1.68, 95% confidential interval:1.08–2.63, p = 0.02) was associated with normal weight insulin resistance independently of macrosomia, free fatty acids, triglycerides, remnant-like particle cholesterol and resting pulse rate. In conclusion, normal weight IR phenotype may be associated with increased plasma leptin concentrations and leptin to fat mass ratio in young Japanese women, suggesting higher leptin production by body fat unit.

Effect of growth rates on hormonal and pubertal status in Nellore heifers early weaned.

This study aimed to determine the effect of growth rates on the hormonal status and puberty onset. Forty-eight Nellore heifers were weaned at 3.0 ± 0.1 (means ± standard error of the mean) months old were blocked according to body weight at weaning (84 ± 2 kg) and randomly assigned to treatments. The treatments were arranged in 2 × 2 factorial according to the feeding program. The first program was high (H; 0.79 kg/day) or control (C; 0.45 kg/day) average daily gain (ADG) from 3rd to 7th month of age (growing phase I). The second program was also high (H; 0.70 kg/day) or control (C; 0.50 kg/day) ADG from the 7th month until puberty (growing phase II), resulting in four treatments: HH (n = 13), HC (n = 10), CH (n = 13), and CC (n = 12). To achieve desired gains, heifers in high ADG program were fed ad libitum dry matter intake (DMI), and the control group was offered around 50% of ad libitum DMI of high group. All heifers received a diet with similar composition. Puberty was assessed weekly by ultrasound examination, and the largest follicle diameter was evaluated every month. Blood samples were collected to quantify leptin, insulin growth factor-1 (IGF1) and luteinizing hormone (LH). At 7 months of age, heifers in high ADG were 35 kg heavier than the control. Heifers in the HH had greater DMI compared with CH in phase II. The puberty rate at 19 months old was greater in the HH treatment (84%) than in the CC (23%), but there was no difference between HC (60%) and CH (50%) treatments. Heifers from HH treatment had greater serum leptin concentration than others at 13 months old, and serum leptin was greater in HH compared with CH and CC at 18 months old. High heifers in phase I had greater serum IGF1 concentration than the control. In addition, HH heifers had a greater diameter of the largest follicle than CC. There was no interaction between phases and age in any variable relative to the LH profile. However, the heifers' age was the main factor that increased the frequency of LH pulse. In conclusion, increasing ADG was associated with greater ADG, serum leptin and IGF-1 concentration, and puberty onset; however, LH concentration was affected mainly by age of the animal. The increasing growth rate at younger age made heifers more efficient.

Association between Maternal Serum Leptin Level and Preterm Birth among Parturients in Lagos, Nigeria

Background: Preterm birth is one of the major causes of neonatal morbidity and mortality worldwide. The association between occurrence of preterm birth and biomarkers measured in the maternal serum maybe helpful in predicting preterm birth especially in low resource settings. Aim: We aimed to examine the association between maternal serum leptin level and occurrence of preterm birth. Materials and Methods: This was an analytical cross-sectional study of women with preterm and term births in Lagos, Nigeria. One hundred and ninety women comprising of 95 women with preterm and term births respectively recruited. Maternal serum leptin levels were determined using Enzyme-linked immunosorbent assay (ELISA) technique. Data was analyzed by Stata version 16 (StataCorp, USA) statistical software with significance level set at p-value &lt;0.05. Results: The mean serum leptin levels were significantly lower in women with preterm delivery compared to women with term delivery (1.48 ng/ml ± 0.72 vs. 1.75 ng/ml ± 0.67, p-value=0.007). On further analysis, women with very preterm birth had significantly lower serum leptin levels compared with women with moderate to late preterm and term births (1.28 ± 0.73 vs 1.55 ± 0.70 vs 1.75ng/ml ± 0.67, p-value=0.006). There was 57% reduction in the odds of having preterm delivery for every unit increase in serum leptin level on multivariate analysis (adjusted OR: 0.43, 95%CI: 0.26 – 0.71, P-value=0.001). Conclusion: Serum leptin concentration was significantly lower in women who had preterm births compared to women who had term births. Longitudinal studies are required to determine the predictive value of maternal serum leptin level with regards to preterm birth.

Influence of Pre-Pregnancy Obesity on Carbohydrate and Lipid Metabolism with Selected Adipokines in the Maternal and Fetal Compartment

A higher body mass index (BMI) before pregnancy is associated with an increased risk of maternal and perinatal complications. This study aimed to analyze selected parameters of carbohydrate and lipid metabolism, including adipokines, in obese pre-pregnant women, and their influence on the birth weight of newborns. Materials and Methods: The study group (O) consisted of 34 pregnant women with higher BMI (obese) before pregnancy. The control group (C) was 27 pregnant women with target BMI and physiological pregnancy. The BMI index: body weight [kg]/(height [m]2 was assessed on the first obstetrical visit. The research material was the serum of pregnant women collected in the third trimester of pregnancy and umbilical cord blood collected immediately after delivery. Selected parameters of carbohydrate and lipid metabolism and adipokines were determined. Results: There were no statistically significant differences between the study group and the control group concerning the concentrations of insulin, glucose, VLDL, adiponectin, TNF-α, HOMA-IR, as well as LDH and cholesterol in maternal blood serum and umbilical cord blood serum. Total cholesterol and HDL in both maternal blood serum and umbilical cord blood were statistically significantly lower than those in the control group. The concentration of triglycerides (TG) and resistin in the blood serum of obese mothers were higher than those in the control group (p &lt; 0.05). However, no statistically significant differences were found between the two groups regarding the concentrations of TG and resistin in the umbilical cord blood. The concentration of LDL cholesterol in the umbilical blood serum in the obese group was statistically significantly lower than that in the control group. The concentration of leptin in maternal blood serum and umbilical cord blood serum in the study group was statistically significantly higher than that in the control group. Conclusions: Pregestational obesity does not substantially affect the basic parameters of carbohydrate metabolism in pregnant women, but it disturbs the lipid profile, which is manifested by a significant increase in triglycerides and a decrease in the level of HDL cholesterol in the serum. Preexisting obesity increases the concentration of leptin and resistin in the serum of pregnant women, which may be caused by the increased volume of adipose tissue. The concentrations of leptin and resistin in the blood of pregnant women correlate positively, and the concentrations of adiponectin and TNF-α negatively correlate with pre-pregnancy BMI values. There is a positive correlation between the concentration of leptin in the serum of umbilical cord blood and the birth weight of the newborn, which suggests that this parameter contributes to the pathomechanism of macrosomia.

Serum leptin, estradiol and testasterone concentrations in normal healthy fertile women with different weights

Background: Leptin, the product of the ob gene, is a hormone secreted by adipocytes. Animals with mutations in the ob gene are obese, leptin affects not only nutritional homeostasis but also reproductive events. A prospective study was done to investigate serum leptin ,estradiol and testosterone levels in 100 fertile healthy women with regular cycle aged(18-45) years with different weights and to see the influence of obesity on these parameters , the correlation of leptin with body mass index ,waist hip ratio , estradiol and testosterone level was determined. Methods fasting blood samples were obtained for the measurement of all studied parameters. serum concentrations of leptin was measured using ( ELISA) , estradiol and testosterone concentrations measured by ( ELFA ) technique (enzyme linked fluorescent assay)by mividus, the body-mass index was defined as the weight in kilo-grams divided by the square of the height in meters. Results: according to the body mass index (BMI), the women were divided in to 3 groups: Group (1) normal weight(30 women) with BMI≤24.9 kgm2 , group( 2) Overweight(30 women) with BMI=25-29.9 kgm2 , group ( 3) obese (40 women) with BMI≥ 30 kgm2. The mean value ±SD of the weight in normal weight group was (53±5)kg , of overweight group was(65.8 ± 4.7) and of obese group was(91.6±16) so there was a highly significant difference between the 3 groups (p-value=0.000) , the Mean ± SD of waisthip ratio in normal, over weight and obese groups were (0.79 ± 0.06, 0.81 ± 0.03 and 0.84 ± 0.05) respectively and there was significant difference between the 3 groups(p-value=0.04), the leptin mean ± SD of normal ,overweight and obese groups were(12.4±6.7, 18.2±5.8 and 24.4±16.4) respectively, and p-value =0.000. Estradiol mean±SD of normal ,overweight and obese groups were (46.2±30.2 ,54.6±25 and79.9 ±52.7)respectively ,p-value =0.03,Testosterone mean±SD of normal, overweight and obese groups were (0.14±0.06, 0.16±0.07 and 0.2±0.09)respectively, p-value =0.00. Conclusions. Leptin correlate significantly with BMI, WH ratio and estradiol level, the women with higher BMI(obese) has higher level of leptin, estradiol and testosterone so the leptin clearly appears to be linked to the reproductive system .

Correlations between Cognitive Evaluation and Metabolic Syndrome.

One of the most common medical diseases is metabolic syndrome (MetS), which encompasses diabetes and obesity. It has a systemic effect, which has long-lasting consequences on the body that are still not fully understood. The objectives of the study were to investigate the association between the severity of metabolic imbalances, insulin resistance, leptin concentration, and the presence of cognitive disorders and to assess the possible protective role of some classes of drugs used in the treatment of type 2 diabetes mellitus (T2D) and dyslipidemia in order to identify a viable target in the near future. The study included 148 diabetic patients. Standardized tests for the evaluation of cognition, including Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), were applied to all study participants. Serum concentrations of leptin and insulin were determined using the enzyme-linked immunosorbent assay method (ELISA), and insulin resistance was calculated using the homeostatic model assessment for insulin resistance (HOMA-IR). We found that MMSE and MoCA scores were associated with anthropometric parameters, and MoCA was associated with glycemic control parameters and leptin levels. Further research is needed in order to establish the magnitude of the relationship between metabolic syndrome components and cognitive decline in diabetic patients.

Associations between Oxidant/Antioxidant Status and Circulating Adipokines in Non-Obese Children with Prader-Willi Syndrome.

Oxidative stress is implicated in the pathophysiology of Prader-Willi syndrome (PWS), but there are no data on these disorders in non-obese children with PWS. Therefore, the presented study examined total oxidant capacity (TOC), total antioxidant capacity (TAC), the oxidative stress index (OSI), and adipokine levels in 22 non-obese children with PWS during dietary intervention and growth hormone treatment compared with 25 non-obese healthy children. Serum concentrations of TOC, TAC, nesfatin-1, leptin, hepcidin, ferroportin, and ferritin were determined using immunoenzymatic methods. We found that TOC concentrations were higher by 50% (p = 0.006) in patients with PWS than in healthy children, but no significant differences in TAC concentrations were observed between these groups. The OSI was higher in children with PWS than in the controls (p = 0.002). We found positive associations between TOC values and the percentage of the Estimated Energy Requirement, body mass index (BMI) Z-score, percentage of fat mass, and leptin, nesfatin-1, and hepcidin concentrations in patients with PWS. A positive association was also found between the OSI and nesfatin-1 levels. These observations suggest that higher daily energy intake and weight gain may be accompanied by an increasing prooxidant state in these patients. Adipokines such as leptin, nesfatin-1, or hepcidin may also play a role in the prooxidant state in non-obese children with PWS.

Functional state of the glutathione system in the adipose tissue of rats with metabolic syndrome

Aim: To study the functional state of the components of the glutathione-dependent antioxidant system in the adipose tissue of rats with experimental metabolic syndrome (MetS).Material and Methods. The MetS model was carried out on male Wistar rats using a high-fat, high-carbohydrate diet (HFHCD). Body and adipose tissue weight were measured. Blood serum levels of glucose, insulin, leptin, triacylglycerides and cholesterol were assessed. In epididymal adipose tissue the level of reactive oxygen species (ROS) was determined by fluorescent method. The concentration of reduced (GSH) and oxidized (GSSG) glutathione, activity of glutathione reductase, glutathione peroxidase, and glutathione-S-transferase enzymes were assessed spectrophotometrically in epididymal adipose tissue.Results. It was found that HFHCD led to an increase in body weight, obesity, hyperglycemia, insulin resistance, dyslipidemia, and leptinemia in the experimental group rats. An increase in adipose tissue mass had a positive correlation with an increase in the concentration of glucose, serum leptin, and ROS levels in the epididymal adipose tissue of rats with MetS. It was found that the level of total glutathione in the adipose tissue of the experimental group rats decreased mainly due to a decrease in the level of GSH. The rats receiving HFHCD also showed a decrease in the activity of glutathione peroxidase and glutathione-S-transferase, but the activity of glutathione reductase increased.Conclusion. Obesity, as a key component of MetS, is a trigger of insulin resistance, chronic low-grade inflammation and oxidative stress. The study showed that the development of MetS and obesity in the experimental animal group is accompanied by a shift of adipocyte redox balance toward oxidative stress, which is expressed in a decrease of GSH/GSSG ratio and glutathione-dependent antiperoxide protection enzymes activity.

Maternal obesity driven changes in collagen linearity of breast extracellular matrix induces invasive mammary epithelial cell phenotype

Obesity has been linked with numerous health issues as well as an increased risk of breast cancer. Although effects of direct obesity in patient outcomes is widely studied, effects of exposure to obesity-related systemic influences in utero have been overlooked. In this study, we investigated the effect of multigenerational obesity on epithelial cell migration and invasion using decellularized breast tissues explanted from normal female mouse pups from a diet induced multigenerational obesity mouse model. We first studied the effect of multigenerational diet on the mechanical properties, adipocyte size, and collagen structure of these mouse breast tissues, and then, examined the migration and invasion behavior of normal (KTB-21) and cancerous (MDA-MB-231) human mammary epithelial cells on the decellularized matrices from each diet group. Breast tissues of mice whose dams had been fed with high-fat diet exhibited larger adipocytes and thicker and curvier collagen fibers, but only slightly elevated elastic modulus and inflammatory cytokine levels. MDA-MB-231 cancer cell motility and invasion were significantly greater on the decellularized matrices from mice whose dams were fed with high-fat diet. A similar trend was observed with normal KTB-21 cells. Our results showed that the collagen curvature was the dominating factor on this enhanced motility and stretching the matrices to equalize the collagen fiber linearity of the matrices ameliorated the observed increase in cell migration and invasion in the mice that were exposed to a high-fat diet in utero. Previous studies indicated an increase in serum leptin concentration for those children born to an obese mother. We generated extracellular matrices using primary fibroblasts exposed to various concentrations of leptin. This produced curvier ECM and increased breast cancer cell motility for cells seeded on the decellularized ECM generated with increasing leptin concentration. Our study shows that exposure to obesity in utero is influential in determining the extracellular matrix structure, and that the resultant change in collagen curvature is a critical factor in regulating the migration and invasion of breast cancer cells.

РОЛЬ ЛЕПТИНА ПРИ РАЗЛИЧНОЙ ВОЗРАСТ-АССОЦИИРОВАННОЙ ПАТОЛОГИИ В СТАРЧЕСКОМ ВОЗРАСТЕ И У ДОЛГОЖИТЕЛЕЙ

Introduction. Leptin is an adipokine synthesized by adipose tissue. This substance is involved in the development of some age-related pathological conditions. Aim. Determination of leptin concentration and analysis of the relationship of this adipokine with obesity and other pathological conditions in elderly patients and centenarians. Material and methods. This work was a cross-sectional study. 110 very elderly patients and centenarians were enrolled in the study: 90 with coronary artery disease – in the study group, 20 without coronary artery disease– in the control group. The mean age of study patient was 88.5+4.5 years. The serum leptin concentration was determined by enzyme-linked immunosorbent assay. Normal leptin values for women were 2.6-11.1 ng/ml, for men – 2.0-5.6 ng/ml. Results and discussion. Elevated leptin levels were found in 58.2% of patients, decreased – in 16.4%, normal – in 25.4%. In patients with coronary artery disease the mean concentration of leptin reached 16.7 ng/ml, in patients without coronary artery disease– 15.3 ng/ml (p=0.6). In patients with chronic heart failure the probability of detecting low leptin levels increased by 3.2 times, compared with patients without heart failure (OR=3.2; 95% CI=1.1-9.9; p=0.03). In patients with obesity the mean leptin level was 28.5 ng/ml, while in patients without obesity – 12.2 ng/ml (p=0.00002). The significant correlation was found between the leptin concentration and body mass index (p&lt;0.000001), as well as fat mass (p=0.000001). Higher leptin levels were observed in patients with diabetes mellitus (26.3 ng/ml vs 13.5 ng/ml in patients without diabetes mellitus, p=0.0003). In patients with low leptin concentration lower bone mineral density was registered (p=0.0003). Conclusion. The study results suggest frequent leptin pathology in very elderly patients and centenarians, both with and without coronary artery disease. Higher leptin levels are associated with various metabolic disorders. Lower leptin levels are typical for patients with chronic heart failure.

Sexually dimorphic pubertal development and adipose tissue kisspeptin dysregulation in the obese and preeclamptic-like BPH/5 mouse model offspring.

Preeclampsia (PE) is a devastating hypertensive disorder of pregnancy closely linked to obesity. Long-term adverse outcomes may occur in offspring from preeclamptic pregnancies. Accordingly, sex-specific changes in pubertal development have been described in children from preeclamptic women, but the underlying mechanisms remain vastly unexplored. Features of PE are spontaneously recapitulated by the blood pressure high subline 5 (BPH/5) mouse model, including obesity and dyslipidemia in females before and throughout pregnancy, superimposed hypertension from late gestation to parturition and fetal growth restriction. A sexually dimorphic cardiometabolic phenotype has been described in BPH/5 offspring: while females are hyperphagic, hyperleptinemic, and overweight, with increased reproductive white adipose tissue (rWAT), males have similar food intake, serum leptin concentration, body weight and rWAT mass as controls. Herein, pubertal development and adiposity were further investigated in BPH/5 progeny. Precocious onset of puberty occurs in BPH/5 females, but not in male offspring. When reaching adulthood, the obese BPH/5 females display hypoestrogenism and hyperandrogenism. Kisspeptins, a family of peptides closely linked to reproduction and metabolism, have been previously shown to induce lipolysis and inhibit adipogenesis. Interestingly, expression of kisspeptins (Kiss1) and their cognate receptor (Kiss1r) in the adipose tissue seem to be modulated by the sex steroid hormone milieu. To further understand the metabolic-reproductive crosstalk in the BPH/5 offspring, Kiss1/Kiss1r expression in male and female rWAT were investigated. Downregulation of Kiss1/Kiss1r occurs in BPH/5 females when compared to males. Interestingly, dietary weight loss attenuated circulating testosterone concentration and rWAT Kiss1 downregulation in BPH/5 females. Altogether, the studies demonstrate reproductive abnormalities in offspring gestated in a PE-like uterus, which appear to be closely associated to the sexually dimorphic metabolic phenotype of the BPH/5 mouse model.

Significant Interactions between Adipokines and Vitamin D Combined with the Estimated Glomerular Filtration Rate: A Geriatric Case Study

Vitamin D deficiency is an important issue in the worldwide population, especially in older people. According to the World Health Organization data, in 2030, 1 in 6 people in the world will be 60 years old or older. The main storage site for vitamin D is adipose tissue. Further, 25(OH)D regulates the expression of adipogenic genes and apoptosis of adipocytes and directly influences the secretion of the appetite-regulating hormone-leptin. Thus, we investigated the impact of the serum concentrations of leptin, adiponectin, omentin, ghrelin, visfatin, and biochemical parameters on vitamin D and estimated glomerular filtration rate (eGFR) in geriatric females. Our studies indicate that the leptin, visfatin and ghrelin are linked with vitamin D concentration and the eGFR rate in the geriatric females. (1) Background: Vitamin D deficiency is common in older people, and researchers are looking for a link between vitamin D deficiency and the occurrence of diseases in advanced age. The study aimed to evaluate the association between serum 25(OH)D levels and clinical variables in older females. (2) Methods: We investigated the impact of the serum concentrations of leptin, adiponectin, omentin, ghrelin, visfatin, and biochemical parameters on vitamin D and estimated the glomerular filtration rate (eGFR) in 74 geriatric females. (3) Results: We observed a significantly higher concentration of creatinine and visfatin in the G2 stage (eGFR = 60-89 mL/min./1.73 m2). We performed an additional analysis to exclude the effect of vitamin D supplementation and obtained a significantly higher vitamin D concentration in the G2 stage. We found significantly lower vitamin D concentrations in older people. In addition, in a person with low levels of vitamin D, we observed significantly lower levels of albumin and ghrelin. Older patients (80 to 89 years old) had significantly lower levels of vitamin D, albumin, insulin, HOMA-IR, and ghrelin than younger patients (60 to 69 years old). Spearman's correlations performed to examine the relationship between clinical variables seemed to confirm previous results. According to ROC curve analysis, leptin concentration was the strongest predictor of vitamin D fluctuations (the area under the curve, AUC = 0.685; with 79.5% sensitivity and 51.4% specificity; p = 0.0291). However, visfatin reached the most accurate AUCROC = 0.651 with 84.2% sensitivity and 49.1% specificity for predicting effects on eGFR. (4) Conclusions: The results suggest that serum levels of leptin, visfatin, and ghrelin are linked with vitamin D concentration and the eGFR rate in the population of geriatric females.

The Effect of Serum Leptin Concentration and Leptin Receptor Expression on Colorectal Cancer.

The level of leptin in the blood shows a positive, strong correlation with the mass of adipose tissue. Being overweight and having metabolic disorders increase the risk of developing colorectal cancer. The aim of the study was to assess the concentration of leptin in the blood serum as well as the expression of the leptin receptor in colorectal cancer cells. In addition, the effect of serum leptin concentration and leptin receptor expression on clinical and pathological parameters such as BMI, obesity, TNM, and tumor size was assessed. The study included 61 patients diagnosed with colorectal cancer and treated with surgery. Strong leptin receptor expression and the prevalence of overweight and obesity are factors influencing the occurrence of excessive leptin concentrations. Leptin may be involved in the development and progression of colorectal cancer. More research is needed to better elucidate the role of leptin in the development and progression of the disease.

A comparison of average daily gain, apparent digestibilities, energy balance, rumen fermentation parameters, and serum metabolites between yaks (Bos grunniens) and Qaidam cattle (Bos taurus) consuming diets differing in energy level.

Yaks (Bos grunniens), indigenous to the harsh Qinghai-Tibetan Plateau, are well adapted to the severe conditions, and graze natural pasture without supplements all year round. Qaidam cattle (Bos taurus), introduced to the Qinghai-Tibetan Plateau 1,700 years ago, are raised at a lower altitude than yaks, provided with shelter at night and offered supplements in winter. Based on their different backgrounds, we hypothesized that yaks have lower energy requirements for maintenance than cattle. To test this hypothesis, we measured average daily gain (ADG), apparent digestibilities, energy balance, rumen fermentation parameters, and serum metabolites in growing yaks and cattle offered diets differing in metabolizable energy (ME) levels (6.62, 8.02, 9.42 and 10.80MJ/kg), but with the same crude protein concentration. Six castrated yaks (155±5.8kg) and 6 castrated Qaidam cattle (154±8.0kg), all 2.5 years old, were used in 2 concurrent 4×4 Latin square designs. Neutral and acid detergent fiber digestibilities were greater (P<0.05) in yaks than in cattle, and decreased linearly (P<0.05) with increasing dietary energy level; whereas, digestibilities of dry matter, organic matter, crude protein and ether extract increased (P<0.05) linearly with increasing energy level. The ADG was greater (P<0.001) in yaks than in cattle, and increased (P<0.05) linearly with increasing energy levels. From the regressions of ADG on ME intake, the estimated ME requirement for maintenance was lower (P<0.05) in yaks than in cattle (0.43 vs. 0.57MJ/kg BW0.75). The ratios of digestible energy (DE):gross energy and ME:DE were higher (P<0.05) in yaks than in cattle, and increased (P<0.05) linearly with increasing dietary energy level. Ruminal pH decreased (P<0.05), whereas concentrations of total volatile fatty acids (VFAs) and ammonia increased (P<0.01) with increasing dietary energy level, and all were greater (P<0.05) in yaks than in cattle. Concentrations of ruminal acetate and iso-VFAs were greater (P<0.05), whereas propionate was lower (P<0.05) in yaks than in cattle; acetate decreased (P<0.001), whereas butyrate and propionate increased (P<0.001) linearly with increasing dietary energy level. Serum concentrations of β-hydroxybutyrate were lower (interaction, P<0.001) in yaks than in cattle fed diets of 9.42 and 10.80MJ/kg, whereas non-esterified fatty acids were greater (interaction, P<0.01) in yaks than in cattle fed diets of 6.62 and 8.02MJ/kg. Concentrations of serum leptin and growth hormone were greater in yaks than in cattle and serum insulin and growth hormone increased (P<0.01) linearly with increasing dietary energy level. Our hypothesis that yaks have lower energy requirements for maintenance than cattle was supported. This lower requirement confers an advantage to yaks over Qaidam cattle in consuming low energy diets during the long winter on the Qinghai-Tibetan Plateau.