Plasma Leptin Research Articles

Polyphenol-rich jaboticaba (Myrciaria jaboticaba) peel and seed powder induces browning of subcutaneous white adipose tissue and improves metabolic status in high-fat-fed mice

In the present study, we investigated the effects of polyphenol-rich jaboticaba peel and seed powder (JPSP) supplementation for four weeks in a concentration-dependent manner (5 %, 10 %, and 15 %) in the adipose tissue and the metabolic status of diet-induced obese mice. JPSP prevents weight gain and adiposity induced by HF diet consumption, reduced plasma leptin concentration, improved insulin sensitivity, and also leads to recovery of brown adipose tissue (BAT) function with increased gene expression levels of UCP1, PPAR-γ, and PGC1-α expression. JPSP consumption promoted browning in subcutaneous with adipose tissue (sWAT) observed with the appearance of specific transcription factors like UCP-1, PRDM16, and ABRB3 in groups supplemented with 10 % and 15 % of JPSP. Thus, these findings indicate that JPSP supplementation could lead to attenuation of obesity complications promoting browning in sWAT and may recovery/improve BAT function, and may be a promising strategy to lessen adiposity and/or improve obesity-mediated metabolic complications.

Developmental exposure to indoor flame retardants and hypothalamic molecular signatures: Sex-dependent reprogramming of lipid homeostasis.

Polybrominated diphenyl ethers (PBDEs) are a class of flame-retardant organohalogen pollutants that act as endocrine/neuroendocrine disrupting chemicals (EDCs). In humans, exposure to brominated flame retardants (BFR) or other environmentally persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) and novel organophosphate flame retardants has been associated with increasing trends of diabetes and metabolic disease. However, the effects of PBDEs on metabolic processes and their associated sex-dependent features are poorly understood. The metabolic-disrupting effects of perinatal exposure to industrial penta-PBDE mixture, DE-71, on male and female progeny of C57BL/6N mouse dams were examined in adulthood. Dams were exposed to environmentally relevant doses of PBDEs daily for 10 weeks (p.o.): 0.1 (L-DE-71) and 0.4 mg/kg/d (H-DE-71) and offspring parameters were compared to corn oil vehicle controls (VEH/CON). The following lipid metabolism indices were measured: plasma cholesterol, triglycerides, adiponectin, leptin, and liver lipids. L-DE-71 female offspring were particularly affected, showing hypercholesterolemia, elevated liver lipids and fasting plasma leptin as compared to same-sex VEH/CON, while L- and H-DE-71 male F1 only showed reduced plasma adiponectin. Using the quantitative Folch method, we found that mean liver lipid content was significantly elevated in L-DE-71 female offspring compared to controls. Oil Red O staining revealed fatty liver in female offspring and dams. General measures of adiposity, body weight, white and brown adipose tissue (BAT), and lean and fat mass were weighed or measured using EchoMRI. DE-71 did not produce abnormal adiposity, but decreased BAT depots in L-DE-71 females and males relative to same-sex VEH/CON. To begin to address potential central mechanisms of deregulated lipid metabolism, we used RT-qPCR to quantitate expression of hypothalamic genes in energy-regulating circuits that control lipid homeostasis. Both doses of DE-71 sex-dependently downregulated hypothalamic expression of Lepr, Stat3, Mc4r, Agrp, Gshr in female offspring while H-DE-71 downregulated Npy in exposed females relative to VEH/CON. In contrast, exposed male offspring displayed upregulated Stat3 and Mc4r. Intestinal barrier integrity was measured using FITC-dextran since it can lead to systemic inflammation that leads to liver damage and metabolic disease, but was not affected by DE-71 exposure. These findings indicate that maternal transfer of PBDEs disproportionately endangers female offspring to lipid metabolic reprogramming that may exaggerate risk for adult metabolic disease.

Blood Profile, Hormones, and Telomere Responses: Potential Biomarkers in Horses Exhibiting Abnormal Oral Behavior

The high prevalence of abnormal oral behavior (AOB) in working horses has been linked to management issues and the pathophysiology of this behavior remains unclear. Therefore, this study aims to elucidate the blood profile, hormones, and telomere length responses between low and high levels of AOB among different horse working groups. A total of 207 healthy horses from various breeds were initially selected from four working groups (leisure riding, equestrian, endurance, and patrolling) and observed for the time spent on AOB. Then, six horses each with higher and lower AOB than the population means were randomly selected from each of the working groups and categorized as high and low AOB horses, respectively. Blood samples were collected for hematology, biochemistry, cortisol, ghrelin, leptin, and relative telomere length analyzes. High AOB horses notably had higher values of glucose, alanine aminotransferase (ALT), alkaline phosphatase (ALP), and creatine kinase (CK) compared to low AOB horses. High AOB horses also recorded higher plasma cortisol and ghrelin, but lower leptin concentrations. Among working groups, both endurance and patrolling horses presented the highest values in sodium, potassium, chloride, phosphate, ALT, and CK. While patrolling horses had the lowest levels of urea, ALP, and albumin levels, equestrian and leisure horses recorded the highest and lowest plasma cortisol and leptin concentrations, respectively. Finally, the telomere length of endurance and patrolling horses were significantly greater than leisure and equestrian horses. The present findings suggest that AOB horses had distinctive physiological characteristics that could be linked to improper diet and a demanding workload, while ghrelin and leptin hormones could be potential biomarkers for this behavior.

Female and male C57BL/6J offspring exposed to maternal obesogenic diet develop altered hypothalamic energy metabolism in adulthood.

Maternal obesity is exceedingly common and strongly linked to offspring obesity and metabolic disease. Hypothalamic function is critical to obesity development. Hypothalamic mechanisms causing obesity following exposure to maternal obesity have not been elucidated. Therefore, we studied a cohort of C57BL/6J dams, treated with a control or high-fat-high-sugar diet, and their adult offspring to explore potential hypothalamic mechanisms to explain the link between maternal and offspring obesity. Dams treated with obesogenic diet were heavier with mild insulin resistance, which is reflective of the most common metabolic disease in pregnancy. Adult offspring exposed to maternal obesogenic diet had no change in body weight but significant increase in fat mass, decreased glucose tolerance, decreased insulin sensitivity, elevated plasma leptin, and elevated plasma thyroid-stimulating hormone. In addition, offspring exposed to maternal obesity had decreased energy intake and activity without change in basal metabolic rate. Hypothalamic neurochemical profile and transcriptome demonstrated decreased neuronal activity and inhibition of oxidative phosphorylation. Collectively, these results indicate that maternal obesity without diabetes is associated with adiposity and decreased hypothalamic energy production in offspring. We hypothesize that altered hypothalamic function significantly contributes to obesity development. Future studies focused on neuroprotective strategies aimed to improve hypothalamic function may decrease obesity development.NEW & NOTEWORTHY Offspring exposed to maternal diet-induced obesity demonstrate a phenotype consistent with energy excess. Contrary to previous studies, the observed energy phenotype was not associated with hyperphagia or decreased basal metabolic rate but rather decreased hypothalamic neuronal activity and energy production. This was supported by neurochemical changes in the hypothalamus as well as inhibition of hypothalamic oxidative phosphorylation pathway. These results highlight the potential for neuroprotective interventions in the prevention of obesity with fetal origins.

Abstracts from the NIH Office of Research on Women's Health 2022 Annual BIRCWH Meeting:Building Interdisciplinary Research Careers in Women's Health November 2, 2022

Abstracts from the NIH Office of Research on Women's Health 2022 Annual BIRCWH Meeting:Building Interdisciplinary Research Careers in Women's Health November 2, 2022

Plasma Leptin and Adiponectin after a 4-Week Vegan Diet: A Randomized-Controlled Pilot Trial in Healthy Participants.

Adiponectin and leptin are important mediators of metabolic homeostasis. The actions of these adipokines extend beyond adipocytes and include systemic modulation of lipid and glucose metabolism, nutrient flux, and the immune response to changes in nutrition. Herein, we hypothesized that short-term intervention with a vegan diet might result in an improvement of plasma concentrations of adiponectin and leptin and the leptin/adiponectin ratio. We investigated the response of plasma adiponectin and leptin to a 4-week intervention with a vegan or meat-rich diet and its associations with sex, BMI and nutritional intake. Fifty-three healthy, omnivore participants (62% female, average age 31 years and BMI 23.1 kg/m2) were randomly assigned to a vegan or meat-rich diet for 4 weeks. Plasma adiponectin and leptin were lower in men compared to women both at the beginning and end of the trial. The concentration of adiponectin in women was significantly higher both when comparing their transition from omnivorous to vegan diet (p = 0.023) and also for vegan versus meat-rich diet at the end of the trial (p = 0.001), whereas plasma leptin did not vary significantly. No changes in adiponectin were identified in men, yet an increase in leptin occurred upon their transition from an omnivorous to a meat-rich diet (p = 0.019). Examination of plasma adiponectin/leptin ratio, a proposed marker of cardiovascular risk, did not differ after 4-weeks of dietary intervention. Our study revealed that adiponectin and leptin concentrations are sensitive to short-term dietary intervention in a sex-dependent manner. This dietary modification of leptin and adiponectin not only occurs quickly as demonstrated in our study, but it remains such as published in studies with individuals who are established (long-term) vegetarians compared to omnivorous.

Oxidative and endoplasmic reticulum stress develop adverse metabolic effects due to the high-fat high-fructose diet consumption from birth to young adulthood

AimsThe early postnatal dietary intake has been considered a crucial factor affecting the offspring later life metabolic status. Consistently, this study investigated the oxidative and endoplasmic reticulum (ER) stress interventions in the induction of adverse metabolic effects due to the high-fat high-fructose diet (HFHFD) consumption from birth to young adulthood in rat offspring. Materials and methodsAfter delivery, the dams with their pups were randomly allocated into the normal diet (ND) and HFHFD groups. At weaning, the male offspring were divided into ND-None, ND-DMSO, ND-4-phenyl butyric acid (4-PBA), HFHFD-None, HFHFD-DMSO, and HFHFD-4-PBA groups and fed on their respected diets for five weeks. Then, the drug was injected for ten days. Subsequently, glucose and lipid metabolism parameters, oxidative and ER stress markers, and Wolfram syndrome1 (Wfs1) expression were assessed. Key findingsIn the HFHFD group, anthropometrical parameters, plasma high-density lipoprotein (HDL), and glucose-stimulated insulin secretion and content were decreased. Whereas, the levels of plasma leptin, low-density lipoprotein (LDL) and glucose, hypothalamic leptin, pancreatic catalase activity and glutathione (GSH), pancreatic and hypothalamic malondialdehyde (MDA), binding immunoglobulin protein (BIP) and C/EBP homologous protein (CHOP), and pancreatic WFS1 protein were increased. 4-PBA administration in the HFHFD group, decreased the hypothalamic and pancreatic MDA, BIP and CHOP levels, while, increased the Insulin mRNA and glucose-stimulated insulin secretion and content. SignificanceHFHFD intake from birth to young adulthood through the development of pancreatic and hypothalamic oxidative and ER stress, increased the pancreatic WFS1 protein and impaired glucose and lipid homeostasis in male rat offspring.

Feedlot rearing versus pasture grazing enhances plasma leptin and insulin-like growth factor-1 concentrations but does not anticipate puberty in dairy buffalo (Bubalus bubalis) heifers

Plasma Leptin (LEP) and Insulin-like Growth Factor-1 (IGF-1), related to growth and puberty onset, were assayed in growing buffalo heifers from 8 up to 21 months of age, reared in feedlot (FR, n = 13; initial body weight 132 ± 11 Kg) or grazing at pasture (PG, n = 13; 137 ± 12 Kg). The mean age at puberty was not different between the two groups (599.5 and 610.5 days, in FR and PG, respectively). At puberty, FR heifers showed higher BCS, and higher average daily weight gain (DWG) than PG ones (0.87 vs. 0.62 Kg/day), and were heavier (462 vs. 375 Kg). A negative correlation between DWG and age at puberty was significant for the PG group. Plasma Inhibin-A increased in both groups one month before puberty. Plasma LEP and IGF-1 sharply increased 2 months before puberty (about 18 months old) in FR heifers only, which showed higher concentrations of both hormones than PG heifers. Plasma LEP levels correlated positively with body weight and IGF-1. Despite hormone levels being affected by rearing systems, and being lower in heifers grazing at pasture, these latter experienced adequate growth and reproductive maturation. In fact, grazing heifers reached puberty at the same age as the feedlot reared ones, with shorter puberty–conception interval (51.3 vs. 67.2 days, for PG and FR groups, respectively) and no difference in conception rates (83.3 and 84.6%, for PG and FR groups respectively). The higher BW and DWG of FR heifers were due to body fat deposition, which did not anticipate the puberty onset. Highlights Metabolic hormones Leptin and IGF-1, linked to puberty attainment, are good indicators of the animal energetic state. Buffalo heifers reared in intensive system vs. the ones at pasture had higher hormone levels and growth, but reproductive performance was not better. Post-weaned heifers can be reared at pasture during growth and breeding, without compromising reproductive performance.

The intake of β-sitosterol partially counteracts metformin beneficial effects in diet-induced obese rats

Despite the high coexistence of hyperlipidaemia and the prediabetes state, little is known about the effects of the β-sitosterol and metformin (MET) combination. This study aimed to evaluate the effects of low doses of MET (75 or 150 mg/kg bw; M75 or M150) on western-diet induced obese (WDIO) rats, in combination or not with β-sitosterol (176 mg/kg bw; SIT and N-SIT, respectively). The gains of body weight and body fat mass, calorie food intake and plasma leptin were reduced in M150 animals, both SIT and N-SIT groups. Only N-SIT animals showed that insulin levels and HOMA-IR were reduced in the M150 group. M150 group showed a tendency towards lower mRNA levels of Npy and increased Lepr mRNA levels in hypothalamus, but only in N-SIT animals. In conclusion, these results show that the co-administration of MET with β-sitosterol seems to neutralise part of the beneficial effects of MET in WDIO rats.

Abstract 112: Role Of Endogenous Brain Melanocortin-4 Receptor Activation In Regulating Blood Pressure And Metabolic Function In Offspring Of Parents With Obesity

We previously demonstrated that activation of the central nervous system (CNS) melanocortin system modulates sympathetic nerve activity (SNA) and blood pressure (BP) in obese Zucker rats and spontaneously hypertensive rats (SHRs). In the present study, we examined whether endogenous activation of the brain melanocortin-4 receptors (MC4R) contributes to the regulation of BP and metabolic function in adult male (24-26 weeks-old) obese and lean offspring from parents fed a normal (N) or high fat diet (H). The rats were implanted with telemetry probes to measure BP and heart rate (HR) 24-hrs/day, and an intracerebroventricular (ICV) cannula was placed into the lateral ventricle. After 1 week to recover from surgery and 2 days of control measurements, the MC4R antagonist (SHU-9119) was infused (1 nmol/h, ICV) for 7 days followed by a 7-day recovery period. MC4R antagonism markedly increased food intake in all groups; however, the increase was more pronounced in obese offspring from obese H-fed parents (HH), especially when analyzing the net cumulative increase in food intake during the 7 days of treatment (191±11 vs. 136±14, 65±18 and 72±12 g) compared with obese offspring from lean N-fed parents (NH), lean offspring from obese H-fed parents (HN) and lean offspring from lean parents (NN), respectively. This increased food intake was associated with more weight gain in HH compared with NH, HN and NN offspring (Δ: 92±12 vs. 81±17, 52±11 and 38±9 g). Plasma leptin and insulin levels were markedly increased in HH offspring compared to NH, HN and NN offspring. Compared to NH and NN offspring from lean parents, HH and HN offspring from obese parents exhibited higher baseline mean arterial pressure (125±2 and 122±3 vs. 118±1 and 113±3 mmHg) and greater reduction in BP during SHU-9119 infusion (average last 3 days of infusion: -14.3±0.1 and -5.6±0.5 vs. -9.8±0.2 and -3.4±0.2 mmHg, respectively). The reduction in HR during SHU-9119 infusion, however, was more pronounced in NH and NN groups compared with HH and HN offspring (average last 3 days of infusion: -55±2 and -43±1 vs. -34±2 and -34±1 bpm). These results suggest that endogenous activation of brain MC4R may contribute to the elevated BP in obese offspring but not lean offspring from obese parents.

Maternal and fetal factors affecting cord plasma leptin and adiponectin levels and their ratio in preterm and term newborns: New insight on fetal origins of metabolic dysfunction.

Understanding of maternal and fetal factors affecting leptin, adiponectin, and adiponectin:leptin ratio at birth may provide valuable insights into potential future risk of metabolic alterations and inform primordial prevention and precision nutrition strategies. The objective of this study is to identify maternal and fetal risk factors that affect leptin and adiponectin levels (markers of adiposity) and adiponectin/leptin ratio (a marker of dysfunctional adipose tissue) at birth. We studied mother-infant pairs in the Boston Birth Cohort. Cord blood was collected at birth. We used student t- tests to compare log normalized cord leptin and adiponectin levels. Regression analysis was performed to examine the association of maternal and fetal factors with leptin and adiponectin levels and adiponectin:leptin ratio at birth in both term and preterm infants. We analyzed 1012 infants (245 preterm). Both cord leptin and adiponectin were higher in term infants than preterm infants (10.2 ± 0.9 vs. 9.2 ± 1.3, P < 0.0001 and 9.5 ± 0.7 vs. 8.9 ± 0.8, P < 0.0001, respectively). Cord leptin was higher for Black infants (10.1 ± 1.1 vs. 9.9 ± 1.2; P < 0.001) although Black (ref: non-Black) infants had lower cord adiponectin levels (9.3 ± 0.8 vs. 9.5 ± 0.7; P = 0.01). Ratio of adiponectin to leptin (log normalized) was higher in preterm infants (-0.24) vs. term infants (-0.69). On regression analysis, cord leptin was positively associated with longer gestational age (GA), birth weight z score, Black race, maternal overweight and obesity, gestational diabetes and pregestational diabetes mellitus and negatively associated with male sex. Cord adiponectin was positively associated with GA, birth weight z score and negatively with Black race and male sex. Adiponectin:leptin ratio was positively with male sex and negatively with GA, birth weight z score, Black race, gestational DM, pregestational DM and maternal overweight and obesity. We identified several factors that affect leptin and adiponectin levels along with adiponectin-leptin ratio at birth beyond GA and birth weight which could also play an important role in influencing the trajectory of these hormones and future cardiometabolic outcomes. This knowledge can help tailor precision nutrition interventions.

Adipokine Responses To Exercise Repeated On Successive Days In Men With Metabolic Syndrome

PURPOSE: To examine the temporal responses of adipokines to repeated exercise bouts in successive days in obese males with metabolic syndrome and their relationship with markers of insulin resistance. METHODS: Volunteers were 11 males (age = 50 ± 8.0 years, BMI = 32.0 ± 4.6 kg/m2, Fat = 29 ± 4.0%, VO2max = 28.9 ± 4.3 ml.kg.-1min-1, SBP = 140 ± 8.6 mmHg, DBP = 92 ± 6.3 mmHg, triglyceride = 267 ± 145.0 mg/dL, HDL-C = 32 ± 5.0 mg/dL, glucose = 99.6 ± 12.8 mg/dL), that performed four exercise sessions walking on a treadmill at 60 to 70% of VO2max and expending 350 kcals of energy on each of four successive days. Blood samples were obtained before each exercise session and obtained again at 24 and 72 hours after the last exercise bout. Total and HMW adiponectin, leptin, NEFA, glucose and insulin were determined after adjusting for plasma volume shifts. We used a multiple 1 x 6 repeated-measures ANOVAs to determine significance. RESULTS: Insulin concentrations decreased 26% with a single bout of exercise and leptin decreased 9% after two exercise sessions and remained lower up to 24 hours following the last exercise session. NEFA, glucose, the HOMA score, adiponectin and HMW adiponectin remained unaltered with exercise. The accumulated effect of multiple bouts of exercise in leptin concentrations were greater than the effect obtained from two exercise bouts but not related to changes in insulin concentrations or the HOMA score. CONCLUSION: Plasma leptin concentrations were transiently reduced in obese men with metabolic syndrome and this reduction was maintained up to 24 hours after exercise. Adiponectin and HMW adiponectin were unaltered by exercise. No further change in adipokines and markers of metabolic health were observed after exercise repeated on successive days.

Abstract 108: Altered Erk / Klf4-mediated Control Of Agrp And Metabolic Rate During Obesity

Resting metabolic rate (RMR) adaptation contributes to the maintenance of human obesity, yet mechanisms controlling RMR in lean vs obese states remain poorly defined. Leptin contributes to RMR control in part through suppression of inhibitory Agouti-related peptide (AgRP) neurotransmission in the hypothalamic arcuate nucleus (ARC). Within AgRP neurons, leptin activates the extracellular signal-regulated kinase (ERK) cascade, which is thought to interrupt Agrp transcription through interference with the Krüppel-like factor 4 (KLF4) transcription factor, and our published data support altered ARC ERK signaling during obesity. We therefore hypothesized a role for ERK/KLF4 signaling within AgRP neurons for the suppression of AgRP transcription and thereby stimulation of RMR in the lean state, and changes in this pathway during obesity. In the GT1-7 cell model of AgRP neurons, leptin increased the phosphorylated ERK (pERK)/ERK ratio (n=4, 1 uM, 15 min +89% p&lt;0.05) and reduced Agrp mRNA (n=4, 1 uM, 1 hr -43.0% p&lt;0.05); similarly, siRNA knockdown of Klf4 reduced Agrp mRNA (n=4, -21.6% p&lt;0.05). In lean adult C57BL/6J mice, leptin increased the ARC pERK/ERK ratio (n=8, 1 ug/g ip 16.5-fold p&lt;0.05) and stimulated RMR (n=11, 2 ug/g ip 30 min +43.8% p&lt;0.05). Lean transgenic mice with conditional deletion of KLF4 from AgRP neurons ( Agrp -Cre x Klf4 flox ) exhibited increased RMR (n=13 KO +13.48% vs controls n=22 p&lt;0.05). These findings support the model that ERK inhibition of KLF4 within AgRP neurons mechanistically contributes to leptin-mediated control of Agrp and RMR in the lean state. Ten weeks of high fat feeding strongly increases endogenous plasma leptin in C57BL/6J mice, and this treatment increased the ARC pERK/ERK ratio (n=5 +54.4% p&lt;0.05), yet ARC KLF4 was increased (n=6 +74.6% p&lt;0.05) and Agrp mRNA was not suppressed (n=4 +1.6-fold, p=ns). Therefore, these data also support the concept that loss of ERK-mediated suppression of KLF4 within the AgRP neuron during obesity may contribute to the pathogenesis of RMR adaptation.

Short communication: Photoperiod impacts ovarian extracellular matrix and metabolic gene expression in Siberian hamsters

Ovarian cyclicity is variable in adult Siberian hamsters (Phodopus sungorus), who respond to long breeding season photoperiods with follicle development and ovulation, while short photoperiods typical of the non-breeding season induce gonadal atrophy. Recent RNAseq results identified ovarian matrix components and regulators of metabolism as differentially regulated by photoperiod; however, the impact of photoperiod across a full cycle of ovarian regression and recrudescence had not been explored for additional regulators of ovarian metabolism and extracellular matrix components. We hypothesized that matrix and metabolism-related genes would be expressed differentially across photoperiods that mimic breeding and non-breeding season daylengths. Hamsters were housed in one of four photoperiod groups: long day (16 h of light per day: 8 h of dark; LD, controls), short day regressed (8 L:16D; SD, regressed), and females exposed to SD then transferred to LD to stimulate return of ovarian function for 2 (early recrudescence), or 8 (late recrudescence) weeks. Plasma leptin concentrations along with expression of ovarian versican and liver-receptor homolog-1/Nr582 mRNA decreased in SD compared to LD and late recrudescence, while vimentin mRNA expression peaked in early and late recrudescence. Ovarian expression of fibronectin and extracellular matrix protein-1 was low in LD ovaries and increased in regressed and recrudescing groups. Expression of hyaluronidase-2, nectin-2, liver-X receptors-α and-β, and adiponectin mRNA peaked in late recrudescence, with no changes noted for adiponectin receptor-1 and -2. The results offer a first look at the parallels between expression of these genes and the dynamic remodeling that occurs during ovarian regression and recrudescence.

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.

Fetuin-A mediates the difference in adipose tissue insulin resistance between young adult pakistani and norwegian patients with type 2 diabetes

BackgroundSouth-Asian immigrants to Western countries have a high prevalence of type 2 diabetes mellitus (T2DM) and increased adipose tissue insulin resistance (AT-IR), as compared to their Western counterparts. Fetuin-A is a hepatokine known to influence AT-IR.AimCan plasma fetuin-A concentrations explain an ethnic difference in adipose tissue insulin resistance?MethodsWe performed a two-step euglycemic-hyperinsulinaemic clamp and measured plasma concentrations of fetuin-A and non-esterified fatty acids (NEFA), in 18 Pakistani and 21 Norwegians with T2DM (age 29–45y) in Norway. AT-IR was calculated as NEFA-suppression during the clamp. The adipokines/cytokines leptin, adiponectin, visfatin, PTX3, IL-1β, INF-γ, and IL-4 were measured in fasting plasma. Liver fat was estimated by CT-scans.ResultsDespite a lower BMI, Pakistani patients displayed higher AT-IR than Norwegians. NEFA-suppression during clamp was lower in Pakistani than Norwegians (mean=-20.6%, 95%CI=[-40.8, -0.01] and p = 0.046). Plasma fetuin-A concentration was higher in Pakistani than Norwegians (43.4 ng/mL[12.7,74.0], p = 0.007) and correlated negatively to %NEFA-suppression during clamp (rho=-0.39, p = 0.039). Plasma fetuin-A concentration explained 22% of the ethnic difference in NEFA-suppression during the clamp. Pakistani patients exhibited higher plasma leptin and lower PTX3 levels than Norwegian, and plasma visfatin correlated positively to plasma fetuin-A levels in the Pakistani patients. We observed no correlation between plasma fetuin-A and liver fat, but fetuin-A correlated negatively with plasma IL-1β, INF-γ, and IL-4 concentrations. Plasma IL-4 concentration was lower in Pakistani than in Norwegian patients.ConclusionFetuin-A may contribute to explain the discrepancy in T2DM prevalence between Pakistani and Norwegians patients by influencing AT-IR.

Nonobese Male Patients with Alzheimer's Disease Are Vulnerable to Decrease in Plasma Leptin.

Metabolic dysfunction links to cognitive deficits in Alzheimer's disease (AD). Leptin is an anti-obesity hormone that modulates energy homeostasis and memory function. Although leptin deregulation is implicated in mouse models of AD-like brain pathology, clinical studies have shown inconsistent results regarding an association of leptin with the development of this neurodegenerative disorder. We investigated the changes of plasma leptin and the correlation of sex-stratified circulating leptin with cognitive performance, AD-related biological markers, and metabolic status in patients with AD and cognitively unimpaired (CU) counterparts. We used nonobese AD patients and CU controls in a University of Kansas Medical Center (KUMC) cohort. Plasma leptin levels, circulating AD-related molecules and metabolic profiles were examined and analyzed. In contrast to unchanged circulating leptin in females, male patients exhibited decreased plasma leptin levels compared with male CU counterparts. Moreover, plasma leptin showed no correlation with cognitive performance and AD blood biomarkers in patients with either sex. Of note, females but not males demonstrated an association of plasma leptin with body mass index, high density lipoprotein-cholesterol and its ratio with total cholesterol and triglycerides. Our findings suggest that leptin deficiency is associated with nonobese male AD patients, supporting systemic dysmetabolism in the development of this neurodegenerative disorder in certain populations. Although plasma leptin may have limited capacity to reflect disease severity or progression, future mechanistic studies on the regulation of leptin in nonobese patients with AD would deepen our understanding of the sex-related disparity of AD etiopathogenesis.

Arcuate AgRP, but not POMC neurons, modulate paraventricular CRF synthesis and release in response to fasting

BackgroundThe activation of the hypothalamic–pituitary–adrenal (HPA) axis is essential for metabolic adaptation in response to fasting. However, the neurocircuitry connecting changes in the peripheral energy stores to the activity of hypothalamic paraventricular corticotrophin-releasing factor (CRFPVN) neurons, the master controller of the HPA axis activity, is not completely understood. Our main goal was to determine if hypothalamic arcuate nucleus (ARC) POMC and AgRP neurons can communicate fasting-induced changes in peripheral energy stores, associated to a fall in plasma leptin levels, to CRFPVN neurons to modulate the HPA axis activity in mice.ResultsWe observed increased plasma corticosterone levels associate with increased CRFPVN mRNA expression and increased CRFPVN neuronal activity in 36 h fasted mice. These responses were associated with a fall in plasma leptin levels and changes in the mRNA expression of Agrp and Pomc in the ARC. Fasting-induced decrease in plasma leptin partially modulated these responses through a change in the activity of ARC neurons. The chemogenetic activation of POMCARC by DREADDs did not affect fasting-induced activation of the HPA axis. DREADDs inhibition of AgRPARC neurons reduced the content of CRFPVN and increased its accumulation in the median eminence but had no effect on corticosterone secretion induced by fasting.ConclusionOur data indicate that AgRPARC neurons are part of the neurocircuitry involved in the coupling of PVNCRF activity to changes in peripheral energy stores induced by prolonged fasting.

Sex-Dependent Mediation of Leptin in the Association of Perilipin Polymorphisms with BMI and Plasma Lipid Levels in Children.

Variations in the perilipin (PLIN) gene have been suggested to be associated with obesity and its related alterations, but a different nutritional status seems to contribute to differences in these associations. In our study, we examined the association of several polymorphisms at the PLIN locus with obesity and lipid profile in children, and then analyzed the mediation of plasma leptin levels on these associations. The single-nucleotide polymorphisms (SNPs) rs894160, rs1052700, and rs2304795 in PLIN1, and rs35568725 in PLIN2, were analyzed by RT-PCR in 1264 children aged 6–8 years. Our results showed a contrasting association of PLIN1 rs1052700 with apolipoprotein (Apo) A-I levels in boys and girls, with genotype TT carriers showing significantly higher Apo A-I levels in boys and significantly lower Apo A-I levels in girls. Significant associations of the SNP PLIN2 rs35568725 with high-density lipoprotein cholesterol (HDL-cholesterol), Apo A-I, and non-esterified fatty acids (NEFA) were observed in boys but not in girls. The associations of the SNPs studied with body mass index (BMI), NEFA, and Apo A-I in boys and girls were different depending on leptin concentration. In conclusion, we describe the mediation of plasma leptin levels in the association of SNPs in PLIN1 and PLIN2 with BMI, Apo A-I, and NEFA. Different leptin levels by sex may contribute to explain the sex-dependent association of the PLIN SNPs with these variables.

Association between Leptin (G2548A) and Leptin Receptor (Q223R) Polymorphisms with Plasma Leptin, BMI, Stress, Sleep and Eating Patterns among the Multiethnic Young Malaysian Adult Population from a Healthcare University.

Relative leptin resistance in childhood to absolute leptin resistance in maturity suggests sleep, eating behaviour, and the psychological state as probable causes. The current body of research provides inconclusive evidence linking G2548A and Q223R to obesity. Furthermore, we could find very little data that have observed the association between the environment and gene polymorphism, especially in the multiethnic population that exists in Malaysia. This study searched for a possible link between sleeping habits, eating behaviour, and stress indicators with plasma leptin and its genetic variation in young adult Malaysian healthcare students. The study involved 185 first- and second-year medical and dental students from a healthcare university. Polymerase Chain Reaction–Restriction Fragment Length Polymorphism(PCR-RFLP) determined the genotype, Enzyme Linked Immunoabsorbant Assay (ELISA) tested the serum leptin, and a self-administered questionnaire evaluated sleep, eating behaviour, and psychological condition. Gender and ethnicity are linked to fasting plasma leptin levels (p < 0.001). Plasma leptin also affects stress, anxiety, and sadness. Leptin (LEP) and Leptin Receptor (LEPR) polymorphisms were not associated with BMI, plasma leptin, sleep, eating behaviour, or psychological state. Young adult Malaysian Indians were obese and overweight, while Chinese were underweight. These findings imply overweight and obese participants were in stage I of leptin resistance and lifestyle change or leptin therapy could prevent them from becoming cripplingly obese as they age.