Plasma Leptin Research Articles

1046-P: Role of Serum C1q/TNF-Related Protein 9 in Predicting Gestational Diabetes Mellitus

Background/Aims: C1q/TNF-related protein 9 (CTRP9) as a member of CTRP super family, participates in the regulation of glycolipid metabolism. However information regarding the role of CTRP9 in gestational diabetes mellitus (GDM) is scarce. The current study aims to ascertain the relationship between serum CTRP9 levels and GDM. Methods: A total of 35 GDM patients and 37 normal pregnant women were enrolled in our study. Serum CTRP9 levels were measured via enzyme-linked immunosorbent assay (ELISA) . Fasting insulin (FINS) , IL-6, Leptin, MCP-1, TNF-α and IL-1β were quantified using Luminex-xMAP technology. Anthropometric data and biochemical parameters were also obtained or measured. Results: The results showed that fasting plasma glucose (FPG) , one hour plasma glucose (1-h PG) , 2 hour plasma glucose (2-h PG) , FINS, IL-6, Leptin, TNF-α and CTRP9 during GDM group were significantly higher than the control group. In addition, serum CTRP9 levels had a significantly positive correlation with FPG (r = 0.559, P < 0.001) , 1h-PG (r = 0.539, P <0.0) , 2h-PG (r = 0.378, P = 0.001) , FINS (r = 0.253, P = 0.032) , HOMA-IR (r = 0.382, P = 0.001) , IL-6 (r = 0.283, P = 0.016) , and TNF-α (r = 0.266, P = 0.024) . Furthermore, binary logistic regression demonstrated that HOMA-IR and CTRP9 were independent risk factors for GDM. The AUC-ROC indicated that the diagnostic efficiency of combined CTRP9 and HOMA-IR was much higher than a single index. Conclusions: The high level of serum CTRP9 is an independent risk factor for GDM. Moreover, the combination of serum CTRP9 and HOMA-IR were more efficient in diagnosing GDM. Key words: Gestational diabetes mellitus, CTRP9, insulin resistance Disclosure H. Zhang: None.

Plasma VEGF and Leptin Values in Patients With Gastric Intestinal Metaplasia and Metabolic Syndrome.

Intestinal metaplasia of the stomach (IM) is considered a pre-cancerous lesion and is a potential precursor to adenocarcinoma. Metabolic syndrome (MetS) has been associated with lesions to the gastrointestinal tract such as the risk of developing Barett esophagus. Vascular endothelial growth factor and leptin have been associated with either gastrointestinal tract carcinogenesis or MetS. In this context, this study was designed to analyze plasma levels of VEGF and leptin in patients with IM and MetS. Four groups of 137 participants (a control group and three patient groups, IM, MetS and IM- MetS) were created. Inclusion criteria for the presence of IM were endoscopic findings and histological confirmation, while for MetS the ATP III and IDF guidelines. Levels of plasma vascular endothelial growth factor (VEGF) and leptin (Leptin) were determined. VEGF levels were increased in IM (IM vs Control, p=0,011) and IM-MetS groups (IM-MetS vs Control, p <0.001 and IM-MetS vs MetS, p=0.001). Leptin levels were found to be increased in the MetS group (MetS vs. Control, p <0.001 and MetS vs IM, p <0.001) and in IM-MetS (IM-MetS vs Control, p = 0.002, IM-MetS vs IM, p=0.033). Patients with intestinal metaplasia and metabolic syndrome (I M - Me t S g r o u p) have elevated levels of VEGF, while leptin levels were associated predominantly with MetS and not with IM.

Association of leptin with insulin resistance in type 2 diabetes mellitus

Introduction: Type 2 Diabetes mellitus (T2DM) is a chronic disease that is characterized by impaired glucose metabolism and insulin resistance. Leptin is a 16-kDa protein hormone, which is secreted by adipocytes. Plasma Leptin concentration increases in proportion to body fat mass and regulate food intake and energy expenditure to maintain body fat stores. Leptin binds with a leptin receptor (LEPR) that is located on pancreatic beta cells to regulate insulin secretion. Materials and Methods: This is a prospective and case-control study was conducted in the Department of Biochemistry at Great Eastern Medical School and hospital over a period of 1 year. After the inclusion of participants in the study, their demographics such as age, BMI, gender, and smoking history were noted in self-structured questionnaires. Their blood was drawn and sent to the laboratory for Lipid profile levels, insulin resistance and leptin levels. The serum levels of Leptin were measured using a radioimmunoassay (RIA). Results: The probable association between Leptin and Insulin resistance in type 2 diabetes mellitus. 60 recent onset (&lt;5 years) diabetics and age-sex matched 60 non-diabetic controls were assessed for physical and chemical parameters.

Consumption of Dehulled Adlay Improved Lipid Metabolism and Inflammation in Overweight and Obese Individuals after a 6-Week Single-Arm Pilot Study.

Obesity is a major public health concern worldwide with a rising prevalence. Diets containing whole grains have been demonstrated to benefit body composition and inflammatory conditions in individuals at a high risk of metabolic disorders. This study investigated the effects of dehulled adlay on blood lipids and inflammation in overweight and obese adults. We recruited 21 individuals with abdominal obesity to participate in a 6-week experiment, providing them 60 g of dehulled adlay powder per day as a substitute for their daily staple. Before and after the 6-week intervention, we performed anthropometric analyses and measured blood lipid profiles, adipokines, and markers of inflammation. At the end of the study, the percentage of body fat mass, blood total cholesterol, and triglyceride levels were significantly decreased compared with the baseline. Plasma tumor necrosis factor alpha, interleukin-6, leptin, and malondialdehyde levels were also reduced. In addition, participants with higher basal blood lipid levels exhibited enhanced lipid lowering effects after the dehulled adlay intervention. These results suggest that a dietary pattern containing 60 g of dehulled adlay per day may have a beneficial effect on lipid profiles and inflammatory markers in individuals that are overweight and obese.

Serum leptin level and incidence of CKD: a longitudinal study of adult enrolled in the Korean genome and epidemiology study(KoGES)

BackgroundChronic kidney disease(CKD) is a major public health issue and is highly prevalent in the general population. Leptin is an adipose tissue-derived endocrine factor that has been associated with several metabolic factors involved in cardiovascular diseases. Several studies have investigated the association between leptin and renal diseases so far. But the results are conflicting between the studies. The objective of our study was to verify the direct association of serum leptin level with CKD development.MethodsThis prospective cohort study included 2646 adult aged 40–70 without CKD in the Korean Genome and Epidemiology Study(KoGES) across South Korea from November 2005 to February 2012. The primary outcome was the development of CKD as defined by National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI). Multivariate stepwise logistic regression analysis was done to assess the independent associations, for with the incident of CKD as the dependent variable, in tertiles of leptin values.ResultsAmong 1100 men and 1546 women with 2.8 mean years of follow-up, incidence of CKD was 18(1.63%) for men and 50(3.23%) for women. In the multivariate logistic regression models, individuals in the highest serum leptin tertile showed significant associations with risk of CKD after adjustment compared to the lowest tertiles in the population. The crude odds ratio for trend was 2.95(p = 0.004) for men. After adjusting for age, baseline eGFR variables showed correlation with statistical significance (OR for trend = 2.25, p = 0.037) for men. The same trends were also seen observed in all population and women also, but no statistical significance was found.ConclusionsHigher plasma leptin levels are associated with the incidence of CKD, independent of traditional factors such as age, baseline eGFR. Our results suggest that leptin may partly explain part of the reported association between obesity and kidney disease.

Impact of dietary betaine supplementation on appetite hormones and blood biochemical parameters in Karan Fries heifer during summer in tropics

The present research ascertained variation in plasma levels of ghrelin and leptin, and blood biochemical parameters under summer conditions in Karan Fries (KF) heifers (n=18) supplemented with two levels of betaine. Present appraisal was conducted on Karan Fries heifers selected randomly. Experiment was divided into two phases: Experiment-I (thermoneutral season) and Experiment–II (summer season: hot-dry and hot-humid season). KF heifers were randomly divided into 3 groups (n=6) of Control, Treatment I (Betaine supplemented @ 25 g/d/ animal) and Treatment II (Betaine supplemented @ 50 g/d/animal). Average maximum and minimum environmental temperatures were 23.5°C and 9.9°C and 35.3°C and 22.4°C, during Experiment I and Experiment II respectively.Blood samples were collected at fortnightly intervals. Betaine supplementation at 25 g/d and 50 g/d resulted in significant increase in plasma ghrelin, leptin, protein and cholesterol level and significant decrease in NEFA and triglycerides levels. However non-significant effect on plasma glucose levels were observed on increasing THI

Profile of insulin resistance in adipose tissue of diet induced obese mice in response to anti‐obesity treatment

BackgroundAdipose tissue is an insulin‐responsive organ that contributes to both glucose and lipid metabolism. Insulin resistance (IR) is when insulin‐dependent tissues lose their sensitivity to insulin, resulting in high blood glucose and insulin due to impairment of the negative feedback mechanism. Insulin resistance progress to metabolic disorders like obesity and type 2 diabetes. Sulforaphane (SFN) is a potential anti‐obesity drug under investigation.AimThis study aims to understand the effect of SFN on insulin resistance pathways in adipose tissues of diet induced obese (DIO) mice.MethodsWild‐type CD1 male mice were fed a high‐fat diet (HFD) for 16 weeks to induce obesity. Mice were divided into two groups DIO‐SFN and DIO‐V. DIO mice have been injected via IP route by SFN (5 mg/kg BW) or Vehicle (25μl) for 4 weeks. Daily body weight measurements have been recorded, and glucose tolerance test (GTT) at day 21 after injection and insulin tolerance test (ITT) at day 25 after injection. Subsequently, mice were sacrificed, blood and tissue samples were collected and snap‐frozen instantly. Total RNA was extracted from epididymal white adipose tissue (eWAT). Plasma leptin, insulin, and glucose level were measured, and 84 IR genes in adipose tissues were examined using RT‐PCR array technology.ResultsSFN treatment to DIO mice causes a significant reduction in body weight by 18.4%. Furthermore, SFN causes a significant reduction in circulating leptin concentrations in DIO‐SFN compared to the vehicle‐treated group. SFN is associated with the improvement of GTT and ITT. SFN causes dysregulation of eight genes related to inflammation, adipocytokine signaling, Il‐6, and HMGB1 pathways. SFN treatment causes significant changes in functions related to adipose tissue insulin resistance such as inhibition of chemotaxsis, inflammatory response and lipid accumulation.ConclusionThis study demonstrated that SFN treatment effectively reduces body weight and can ameliorate IR in eWAT via inhibition of pathways mainly related to inflammation, such as adipocytokine signaling, Il‐6, and HMGB1. SFN can be considered a future anti‐obesity drug.

Gastric Bypass Regulates Early Inflammatory Responses in High-Fat Diet-Induced Obese Mice.

Obesity and diabetes are characterized by chronic inflammatory responses. Roux-en-Y gastric bypass (RYGB) is increasingly regarded as an effective approach for the improvement of glucose homeostasis. In this study, we examined the effects of RYGB on the regulation of early inflammatory responses in the liver and adipose tissue in high-fat diet (HFD)-induced obese (DIO) mice. RYGB was performed in DIO mice followed by analyses of adiposity, insulin sensitivity, plasma and tissue cytokines and adipokines, tissue NF-κB and JNK/c-Jun activation, and tissue macrophage and T-cell subsets. We found that RYGB resulted in sustained improvement of adiposity and insulin sensitivity. Plasma insulin and leptin levels were increased in untreated DIO mice and reduced in RYGB mice. RYGB maintained plasma adiponectin levels and inhibited monocyte chemoattractant protein-1 and interleukin 6 in white adipose tissue (WAT) and liver. RYGB inhibited NF-κB activation in WAT and muscle, but not in the liver. However, RYGB attenuated the JNK/c-Jun signaling pathway in the liver and WAT at 1wk after surgery, suggesting that RYGB regulates the tissue-specific inflammatory pathway. RYGB reduced M1-like (F4/80+/CD11c+) differentiation and enhanced M2-like population (F4/80+/CD206c+). RYGB also regulated CD4+ and CD8+ T-cell infiltration and increased Treg cells in the liver and WAT at the same time point. Our findings demonstrate that RYGB improves obesity and insulin resistance, which are associated with the regulation of early inflammatory reactions in the liver and WAT.

Altered ERK‐mediated control of AgRP and metabolic rate during obesity

Adaptation of resting metabolic rate (RMR) contributes to the maintenance of human obesity, yet RMR control and how this system changes during obesity remains poorly defined. Desensitization of the brain to leptin has been proposed to contribute. Leptin normally suppresses Agouti‐related peptide (AgRP) expression in the arcuate nucleus of the hypothalamus (ARC) to disinhibit (increase) melanocortin‐mediated RMR stimulation. Diet‐induced obesity (DIO) increases leptin, but paradoxically exaggerates Agrp expression and causes RMR adaptation. Thus, something connecting leptin to Agrp control becomes dysfunctional during DIO. Our previous data indicate that within the ARC, disruption in the extracellular signal‐regulated kinase (ERK) cascade occurs during DIO. ERK normally phosphorylates Krüppel‐like factor 4 (KLF4), inactivating it. As KLF4 binds to the AgRP promoter to increase transcription, its inactivation results in reduced Agrp expression. We hypothesize that this mechanism becomes dysfunctional within AgRP neurons during DIO, such that KLF4 binding to the AgRP promoter increases despite increased ERK activity.Mouse hypothalamic GT1‐7 cells (model of AgRP neurons) were treated with leptin (1 uM, 15 min or 1 hr) and pERK/ERK ratio was measured by Simple WES and Agrp mRNA expression via qPCR, respectively. Leptin was given to chow‐fed adult mice (2 ug/g ip 30 min) and ARC pERK/ERK ratio was measured, as well as RMR assessed by respirometry. To examine consequences of ERK or KLF4 disruption upon cardiometabolic phenotypes, mice harboring a conditional version of endogenous Mapk1 or Klf4 were crossed with mice expressing Cre via the Agrp locus.In GT1‐7 cells, leptin increased pERK/ERK ratio (1 uM, 15 min leptin n=3, +89% vs vehicle n=2, p&lt;0.05) and suppressed Agrp expression (1 uM, 1 hr leptin n=2, ‐54.1% vs vehicle n=6, p&lt;0.05). In chow‐fed adult mice, leptin injection caused an increase in the ARC pERK/ERK ratio (2 ug/g ip 30 min leptin n=11, +43.8% vs saline n=9, p&lt;0.05). Additionally, leptin stimulated RMR in adult‐chow fed mice (1 ug/g ip leptin n=8, 16.5‐fold of vehicle n=8, p&lt;0.05). DIO caused increases in endogenous plasma leptin and an increase in the ARC pERK/ERK ratio (High Fat Diet (HFD; n=5), +54.4% vs chow n=4, p&lt;0.05), but ARC Agrp expression was not suppressed (HFD n=4, 1.62 fold of chow n=4, p&lt;0.05). There was a possible exaggeration of weight gain in Agrp‐Cre+, Mapk1F/F mice compared to controls following HFD (KOs n=2, +16.8% vs controls n=3). In contrast, weight gain was possibly attenuated in Agrp‐Cre+, Klf4F/F mice compared to controls following HFD (KO n=1, ‐10.7% vs controls n=2). RMR was higher in chow‐fed Agrp‐Cre+, Klf4F/F mice compared to controls (KOs n=5 +8.3% vs controls n=7, p&lt;0.05) and may be exaggerated following HFD (KO n=1 +13.0% vs controls n=3). Together, these findings suggest that ERK and KLF4 within AgRP neurons appear to contribute to the control of AgRP and thus RMR. These findings may identify ERK control of KLF4 and KLF4 as a potential therapeutic target to maintain/restore RMR control after prolonged obesity.

Developing a Mouse Model to Test the Impact of Metabolic Syndrome on Systemic Lupus Erythematosus‐Induced Organ Damage

Background/hypothesis of the studyMetabolic syndrome (MetS) is characterized by a group of conditions that include obesity, impaired glucose tolerance, dyslipidemia and hypertension. MetS is common in systemic erythematosus (SLE) patients and associated with increased cardio‐renal risk. The present study was carried out to develop a model to use in future investigations of whether MetS accelerates SLE‐induced organ damage.Methods and ResultsFemale C57BL/6 mice were untreated or treated epicutaneously with the TLR7 agonist imiquimod (IMQ) and fed a high‐fat (HF) “Western” diet (fat 42% kcal, sucrose 34% kcal) or control diet (fat 12.6% kcal, sucrose 34% kcal) for 6 weeks. Data at 6 weeks were compared by two‐way ANOVA, with n=8 mice per group. Supporting early‐stage induction of autoimmunity, spleen weights were significantly increased in IMQ‐treated mice (PTreatment&lt;0.001), and renal cortex IgG deposition was confirmed by western blot. Increased body weight, gonadal fat pad mass, and plasma leptin levels were observed between HF and control animals (PDiet&lt;0.001) for both IMQ and untreated mice. At the 6th week, HF animals showed an inrease in 24‐hour calorie intake (PDiet&lt;0.05) in contrast to control animals. At the same time, HF diet increased total cholesterol (PDiet&lt;0.05) when compared with control diet‐fed animals. However, the increase in these parameters with HF diet was significantly diminished in IMQ‐treated mice (PDiet*Treatment&lt;0.05). Both the HF diet (PDiet&lt;0.001) and IMQ treatment (PTreatment&lt;0.05) significantly increased fasting blood glucose. IMQ treatment affected fasting insulin concentrations in a diet‐dependent manner (PDiet*Treatment&lt;0.01), with hyperinsulinemia observed in IMQ‐HF treated mice (178±8 μIU/ml) compared to IMQ‐treated control diet mice (49±8 μIU/ml; P&lt;0.05 by Bonferroni post‐hoc test), with plasma insulin similar between untreated mice on HF (112±19 μIU/ml) and control diets (98±20 μIU/ml; P&gt;0.05).ConclusionTogether, these data indicate that the IMQ model of SLE is associated with metabolic alterations, impaired glycemic control, hypercholesterolemia, and hyperinsulinemia under HF intake conditions. In the future, this model may be helpful to understand the complex relationship between MetS and organ damage in SLE.

The Effect of Dietary Fat and Sucrose on Cognitive Functioning in Mice Lacking Insulin Signaling in Neuropeptide Y Neurons.

Obesogenic diets can produce hippocampal insulin resistance and impairments to hippocampal-dependent cognition. This study investigated the effect of disrupted insulin signaling in Neuropeptide Y (NPY) neurons on diet-induced deficits in hippocampal-dependent memory. Wild-type mice and mice that had a targeted knockout of insulin receptors on NPY cells (IRlox/lox;NPYCre/+) were given ad libitum access to a high-fat diet (high fat; HF), 10% sucrose solution (high sugar; HS), both high-fat diet and sucrose solution (high fat, high sugar; HFHS), or a normal fat control chow for 12 weeks. Mice were tested in the Morris Water Maze (MWM), a hippocampal-dependent spatial memory task. Glucose homeostasis was assessed via a glucose tolerance test. Independent of genotype, consumption of HF, but not HS, diet increased energy intake, body weight, and plasma leptin, and impaired glucose tolerance. Disrupted insulin signaling in NPY cells and dietary interventions did not significantly affect the ability of mice to learn the location of the platform in the MWM. However, for IRlox/lox control mice, consumption of HF, but not HS, diet resulted in reduced time spent in the target quadrant during the probe trial, suggesting a hippocampal-dependent memory deficit. IRlox/lox;NPYCre/+ mice had poor performance in the probe trial regardless of diet, suggesting a floor effect. This study did not find adverse effects of chronic sucrose intake on metabolic outcomes or hippocampal-dependent memory. These data also suggest that the effects of HF diet on hippocampal-dependent memory may be dependent on insulin signaling in hippocampal NPY cells.

A fixed single meal in the subjective day prevents free-running of the human sleep-wake cycle but not of the circadian pacemaker under temporal isolation.

Effects of a fixed single meal per day were examined on the circadian pacemaker and sleep-wake cycle in subjects under temporal isolation. When the time of single meal was allowed to take at any time of day (ad-lib meal), the sleep-wake cycle as well as the circadian rhythms in plasma melatonin, cortisol, and core body temperature were significantly phase-delayed in 8 days. On the other hand, when the time of meal was fixed at 1800 h in local time (RF meal), the phase-shift of sleep-wake cycle was not significant while those of the circadian rhythms were significant. The differential effects of a fixed single meal schedule were confirmed in most individual subjects. There was no evidence for the prefeeding increase in plasma cortisol and leptin levels under the fixed single meal schedule. The plasma ghrelin level was apparently high before meal in both ad-lib and RF meal groups, which was, however, likely sculptured by a nonspecific prandial drop and gradual increase after meal intake. Single meal augmented the prandial increase of plasma insulin levels by four to five times. These findings indicate that a single meal at a fixed time of the day during the subjective day failed to prevent the human circadian pacemaker but prevented the sleep-wake cycle from free running for at least 8 days under temporal isolation, suggesting that mealtime was a potent nonphotic time cue for the human sleep-wake cycle.

Fish Oil Enriched n-3 Polyunsaturated Fatty Acids Improve Ketogenic Low-Carbohydrate/High-Fat Diet-Caused Dyslipidemia, Excessive Fat Accumulation, and Weight Control in Rats.

Low-carbohydrate and high-fat diets have been used for body weight (BW) control, but their adverse effects on lipid profiles have raised concern. Fish oil (FO), rich in omega-3 polyunsaturated fatty acids, has profound effects on lipid metabolism. We hypothesized that FO supplementation might improve the lipid metabolic disturbance elicited by low-carbohydrate and high-fat diets. Male SD rats were randomized into normal control diet (NC), high-fat diet (HF), and low-carbohydrate/high-fat diet (LC) groups in experiment 1, and NC, LC, LC + 5% FO (5CF), and LC + 10% FO diet (10CF) groups in experiment 2. The experimental duration was 11 weeks. In the LC group, a ketotic state was induced, and food intake was decreased; however, it did not result in BW loss compared to either the HF or NC groups. In the 5CF group, rats lost significant BW. Dyslipidemia, perirenal and epididymal fat accumulation, hepatic steatosis, and increases in triglyceride and plasma leptin levels were observed in the LC group but were attenuated by FO supplementation. These findings suggest that a ketogenic low-carbohydrate/high-fat diet with no favorable effect on body weight causes visceral and liver lipid accumulation. FO supplementation not only aids in body weight control but also improves lipid metabolism in low-carbohydrate/high-fat diet-fed rats.

Effects of Pumpkin (Cucurbita pepo L.) Seed Protein on Blood Pressure, Plasma Lipids, Leptin, Adiponectin, and Oxidative Stress in Rats with Fructose-Induced Metabolic Syndrome

This study evaluates the potential effects of pumpkin seeds protein on blood pressure (BP), plasma adiponectin, leptin levels, and oxidative stress in rats with fructose-induced metabolic syndrome. Twenty four male Wistar albino rats were divided into four groups and fed a 20% casein diet, 20% casein diet supplemented with pumpkin protein, 20% casein diet with 64% D-fructose, or 20% casein diet with pumpkin protein and 64% D-fructose for 8 weeks. Contin-uous fructose feeding induced an increase in plasma insulin/glucose ratio, BP, insulin and glucose, aspartate aminotrans-ferase, alanine aminotransferase (ALT), alkaline phosphatase (ALP), creatinine, urea, and uric acid levels, and a decrease in the liver and muscle glycogen stores. In addition, elevated levels of total cholesterol (TC), triglycerides (TG), and leptin and lowered adiponectin levels were observed in rats fed a fructose-enriched diet. These groups also exhibited lower plasma levels of ascorbic acid and glutathione, higher thiobarbituric acid-reactive substances, hydroperoxide, carbonyl, and nitric oxide in both the liver and kidneys than rats fed the control diet. Interestingly, pumpkin seed protein treatment significantly counteracted alterations induced by fructose improving glucose, insulin, BP, TG, TC, ALT, and ALP levels, increasing liver and muscle glycogen stores, adiponectin level, and adiponectin/leptin ratio, and reducing plasma leptin lev-els. In addition, rats fed pumpkin protein with a high-fructose diet improved oxidative stress in the liver and kidneys. In conclusion, proteins from Cucurbita pepo L. seeds effectively improve metabolic parameters and protect against oxidative stress induced by a high-fructose diet.

Challenges in rabbit doe feeding, including the young doe

In this review is summarized the last knowledge on rabbit doe nutrition, to complement the current nutritional requirements and strategies for the young and adult rabbit does, considering the production, health, and welfare issues. The rabbit doe must reach an adequate maturity level (body condition) at first artificial insemination (AI) to face its productive life with minimal guarantees (around 7.0 mm of perirenal fat thickness, 2.8 ng/mL of plasma leptin concentration and around 18% and 15-20% of body protein and fat, respectively). This goal can be achieved by restricting feed intake from 12 weeks of age until first AI or feeding ad libitum with a fibrous diet (&lt;10.5 MJ digestible energy/kg) from 60 d of age to first parturition. Once the doe is reproducing, the increase of the n-3 fatty acids (or reduction of the n-6/n-3 ratio), soluble fibre (under epizootic enteropathy) and the Arg/Lys and Gln/Lys ratios may help to improve the reproductive traits of rabbit does, although their optimal level of inclusion remain to be identified. It is recommended to limit an excessive negative energy balance before parturition, and the supplementation of glucose precursors to reduce the ketosis incidence could be useful. The formulation of different diets for the doe and the litter to fit better their requirements and assuring their health would be an option to consider when it would be applicable in the farm. The influence of the mother on the litter microbiota and immune status and its potential modulation through the diet open a new research area that will deserve more studies in the next future.

Association of Serum Leptin with Prognostic Factors in Breast Cancer

Background: Nowadays, cytokines such as Leptin and adiponectin are introduced as prognostic factors which, according to some studies, are also associated with body mass index. This study aimed to determine serum leptin level and its relationship with prognostic factors in breast cancer patients.&#x0D; Methods: This case–control study was conducted in the oncology department of Tohid Hospital, Sanandaj, Iran, between 2019 and 2020. Hundred new cases of breast cancer patients with histological evidence were enrolled in this study. Additionally, 100 age- and BMI-matched healthy individuals were recruited as the control group. The serum leptin level was measured using the ELISA method.&#x0D; Results: Serum leptin levels were significantly higher in breast cancer patients compared to the control group (21.68 ± 9.16 vs 11.89 ± 4.45; p &lt; 0.001). There was no significant relationship between plasma leptin levels with ER, PR, and HER2 expressions (p &gt; 0.05). Also, no significant associations were noted between leptin levels and grading and disease staging (p &gt; 0.05).&#x0D; Conclusion: The study found that leptin is higher in breast cancer patients than in healthy individuals, however, it did not prove that leptin is a predictive or prognostic factor.

LncOb rs10487505 variant is associated with leptin levels in pediatric non-alcoholic fatty liver disease.

Low and high leptin levels are associated with non-alcoholic fatty liver disease (NAFLD). The LncOb rs10487505 variant has been associated with body mass index (BMI), and the C allele was reported as leptin-lowering. We evaluated the association of rs10487505 with leptin levels, liver histology, and surgery-induced weight loss in youths with NAFLD. One-hundred five obese youths with NAFLD, of whom 19 undergoing laparoscopic sleeve gastrectomy (LSG), were analyzed for rs10487505 and leptin circulating levels. The G allele frequency was lower in youths with NAFLD than in controls (p = 0.049). No difference was found in anthropometrics, biochemistry and histology between G allele carriers and CC homozygotes, except for leptin levels (p = 0.016). Leptin correlated with body weight, BMI, BMI-z score, waist circumference, insulin resistance/sensitivity, and triglycerides (p ≤ 0.01). A multivariable regression model including body weight and homeostasis model assessment of insulin resistance was a good predictor of plasma leptin (R2 = 0.45), and the addition of genotype to the model increased the R2 to 0.50. Following LSG, leptin levels and body weight were more reduced in G allele carriers (p < 0.05). LncOb rs10487505 variant was associated with pediatric NAFLD and high leptin levels, and with weight and leptin reduction after LSG in youths. The interplay of environment, genetics and epigenetics is crucial inflating the risk of non-alcoholic fatty liver disease (NAFLD). Several long non-coding RNA (LncRNAs) are found associated with NAFLD pathogenesis. Here, we evaluated the impact of the genetic variant rs10487505 in LncOb which is involved in the regulation of leptin gene expression. The LncOb rs10487505 is associated with increased levels of leptin, but not with liver histology, in youths with NAFLD. The LncOb rs10487505 was also associated with the significant decrease of leptin and body weight after bariatric surgery.

Leptin Receptor Deficiency Results in Hyperphagia and Increased Fatty Acid Mobilization during Fasting in Rainbow Trout (Oncorhynchus mykiss).

Leptin is a pleiotropic hormone known for regulating appetite and metabolism. To characterize the role of leptin signaling in rainbow trout, we used CRISPR/Cas9 genome editing to disrupt the leptin receptor (LepR) genes, lepra1 and lepra2. We compared wildtype (WT) and mutant fish that were either fed to satiation or feed deprived for six weeks. The LepR mutants exhibited a hyperphagic phenotype, which led to heavier body weight, faster specific growth rate, increased viscero- and hepatosomatic indices, and greater condition factor. Muscle glycogen, plasma leptin, and leptin transcripts (lepa1) were also elevated in fed LepR mutant fish. Expression levels of several hypothalamic genes involved in feed regulation were analyzed (agrp, npy, orexin, cart-1, cart-2, pomc-a1, pomc-b). No differences were detected between fed WT and mutants except for pomc-b (proopiomelanocortin-b), where levels were 7.5-fold higher in LepR fed mutants, suggesting that pomc-b expression is regulated by leptin signaling. Fatty acid (FA) content did not statistically differ in muscle of fed mutant fish compared to WT. However, fasted mutants exhibited significantly lower muscle FA concentrations, suggesting that LepR mutants exhibit increased FA mobilization during fasting. These data demonstrate a key role for leptin signaling in lipid and energy mobilization in a teleost fish.

Roles of leptin in initiation of acquired growth hormone resistance and control of metabolism in rainbow trout.

Catabolic conditions often induce concomitant changes in plasma leptin (Lep), growth hormone (GH), and insulin growth factor I (IGF-I) levels in teleost fish, but it is unclear whether these parts of the endocrine system are responding independently or functionally linked. In this study, fasted rainbow trout was used to study the effects of Lep on the GH-IGF-I system and metabolism. Fish were implanted intraperitoneally with recombinant rainbow trout Lep pellets and remained unfed. After 4 days, plasma GH levels were elevated in the Lep-treated fish in a dose-dependent manner; the expression of hepatic igf1 and plasma IGF-I levels were suppressed accordingly. In vitro Lep treatment reversed ovine GH (oGH)-stimulated expression of igf1 and igf2 in hepatocytes isolated from fasted fish, similar to the inhibitory effects of the MEK1/2 inhibitor U0126 treatment. However, Lep treatment alone had no effect on the expression of igfs or oGH-stimulated ghr2a expression in the hepatocytes. These results demonstrate an additive effect of Lep on suppression of IGF-I under catabolic conditions, indicating that Lep is likely involved in initiation of acquired GH resistance. Although the Lep-implant treatment had no effect on standard metabolic rate, it significantly suppressed gene expression of hepatic hydroxyacyl-CoA dehydrogenase, phosphoenolpyruvate carboxykinase, and glucose 6-phosphatase, which are key enzymes in lipid utilization and gluconeogenesis, in different patterns. Overall, this study indicates that the Lep increase in fasting salmonids is an important regulatory component for physiological adaptation during periods of food deprivation, involved in suppressing growth and hepatic metabolism to spare energy expenditure.

Similar effects of milk protein and blends of milk and plant-based protein on appetite-related hormones in 7- to 8-year-old healthy Danish children: secondary analyses from the PROGRO randomised trial.

The effect of different protein sources on the appetite-related hormones in children is largely unknown. We investigated the effect of milk protein versus blends of milk and rapeseed protein on plasma leptin and adiponectin in children. We included 88Danish 7- to 8-year-old children randomised to receive 35g protein/day for 4weeks in 2018 as either milk protein or blends of milk and rapeseed protein (ratio 54:46 or 30:70). Outcomes included absolute and fat mass-adjusted adiponectin and leptin measured at baseline, Weeks 1 and 4. There was no difference in changes in absolute and fat mass-adjusted adiponectin and leptin after 1 or 4weeks between the three groups (p≥0.100). Leptin increased within all groups (p≤0.046). Combining the three groups, leptin and fat mass-adjusted leptin increased by 23% (95% CI 11;35) and 17% (6.4;29) during the intervention respectively (both p≤0.001). Adiponectin variables did not change during the intervention period. There were no differences between milk protein and blends of milk and rapeseed protein on absolute and fat mass-adjusted leptin and adiponectin in healthy children with a habitual intake of milk. However, leptin increased within all three groups. Future studies should further investigate effect on appetite-related hormones of rapeseed protein alone.