Plasma Leptin Research Articles

Deoxyguanosine kinase mutation F180S is associated with a lean phenotype in mice

BackgroundDeoxyguanosine kinase (DGUOK) deficiency is one of the genetic causes of mitochondrial DNA depletion syndrome (MDDS) in humans, leading to the hepatocerebral or the isolated hepatic form of MDDS. Mouse models are helpful tools for the improvement of understanding of the pathophysiology of diseases and offer the opportunity to examine new therapeutic options.MethodsHerein, we describe the generation and metabolic characterization of a mouse line carrying a homozygous DguokF180S/F180S mutation derived from an N-ethyl-N-nitrosourea-mutagenesis screen. Energy expenditure (EE), oxygen consumption (VO2) and carbon dioxide production (VCO2) were assessed in metabolic cages. LC-MS/MS was used to quantify plasma adrenal steroids. Plasma insulin and leptin levels were quantified with commercially available assay kits.ResultsMutant animals displayed significantly lower body weights and reduced inguinal fat pad mass, in comparison to unaffected littermates. Biochemically, they were characterized by significantly lower blood glucose levels, accompanied by significantly lower insulin, total cholesterol, high density lipoprotein and triglyceride levels. They also displayed an almost 2-fold increase in transaminases. Moreover, absolute EE was comparable in mutant and control mice, but EE in mutants was uncoupled from their body weights. Histological examination of inguinal white adipose tissue (WAT) revealed adipocytes with multilocular fat droplets reminiscent of WAT browning. In addition, mRNA and protein expression of Ucp1 was increased. Mutant mice also presented differing mitochondrial DNA content in various tissues and altered metabolic activity in mitochondria, but no further phenotypical or behavioral abnormalities. Preliminary data imply normal survival of DguokF180S/F180S mutant animals.ConclusionTaken together, DGUOK mutation F180S leads to a lean phenotype, with lower glucose, insulin, and lipid levels rendering this mouse model not only useful for the study of MDDS forms but also for deciphering mechanisms resulting in a lean phenotype.

Standardized Ethanol Extract of Cassia mimosoides var. nomame Makino Ameliorates Obesity via Regulation of Adipogenesis and Lipogenesis in 3T3-L1 Cells and High-Fat Diet-Induced Obese Mice.

Obesity is a major cause of conditions such as type 2 diabetes and non-alcoholic fatty liver disease, posing a threat to public health worldwide. Here, we analyzed the anti-obesity effects of a standardized ethanol extract of Cassia mimosoides var. nomame Makino (EECM) in vitro and in vivo. Treatment of 3T3-L1 adipocytes with EECM suppressed adipogenesis and lipogenesis via the AMP-activated protein kinase pathway by downregulating the expression levels of CCAAT/enhancer-binding protein-alpha, peroxisome proliferator-activated receptor (PPAR)-γ, sterol regulatory element-binding protein-1, and fatty acid synthase and upregulating the acetyl-CoA carboxylase. EECM inhibited mitotic clonal expansion during early adipocyte differentiation. Oral administration of EECM for 10 weeks significantly alleviated body weight gain and body fat accumulation in high-fat diet (HFD)-fed mice. EECM mitigated adipogenesis and lipid accumulation in white adipose and liver tissues of HFD-induced obese mice. It regulated the levels of adipogenic hormones including insulin, leptin, and adipokine in the blood plasma. In brown adipose tissue, EECM induced the expression of thermogenic factors such as uncoupling protein-1, PPAR-α, PPARγ co-activator-1α, sirtuin 1, and cytochrome c oxidase IV. EECM restored the gut microbiome composition at the phylum level and alleviated dysbiosis. Therefore, EECM may be used as a promising therapeutic agent for the prevention of obesity.

Insulin Elevates ID2 Expression in Trophoblasts and Aggravates Preeclampsia in Obese ASB4-Null Mice.

Obesity is a risk factor for preeclampsia. We investigated how obesity influences preeclampsia in mice lacking ankyrin-repeat-and-SOCS-box-containing-protein 4 (ASB4), which promotes trophoblast differentiation via degrading the inhibitor of DNA-binding protein 2 (ID2). Asb4-/- mice on normal chow (NC) develop mild preeclampsia-like phenotypes during pregnancy, including hypertension, proteinuria, and reduced litter size. Wild-type (WT) and Asb4-/- females were placed on a high-fat diet (HFD) starting at weaning. At the age of 8-9 weeks, they were mated with WT or Asb4-/- males, and preeclamptic phenotypes were assessed. HFD-WT dams had no obvious adverse outcomes of pregnancy. In contrast, HFD-Asb4-/- dams had significantly more severe preeclampsia-like phenotypes compared to NC-Asb4-/- dams. The HFD increased white fat weights and plasma leptin and insulin levels in Asb4-/- females. In the HFD-Asb4-/- placenta, ID2 amounts doubled without changing the transcript levels, indicating that insulin likely increases ID2 at a level of post-transcription. In human first-trimester trophoblast HTR8/SVneo cells, exposure to insulin, but not to leptin, led to a significant increase in ID2. HFD-induced obesity markedly worsens the preeclampsia-like phenotypes in the absence of ASB4. Our data indicate that hyperinsulinemia perturbs the timely removal of ID2 and interferes with proper trophoblast differentiation, contributing to enhanced preeclampsia.

Maternal Protein Restriction in Rats Alters Postnatal Growth and Brain Lipid Sensing in Female Offspring.

Perinatal nutrition is a key player in the susceptibility to developing metabolic diseases in adulthood, leading to the concept of "metabolic programming". The aim of this study was to assess the impact of maternal protein restriction during gestation and lactation on glucose homeostasis and eating behaviour in female offspring. Pregnant rats were fed a normal or protein-restricted (PR) diet and followed throughout gestation and lactation. Body weight, glucose homeostasis, and eating behaviour were evaluated in offspring, especially in females. Body weight gain was lower in PR dams during lactation only, despite different food and water intakes throughout gestation and lactation. Plasma concentration of leptin, adiponectin and triglycerides increased drastically before delivery in PR dams in relation to fat deposits. Although all pups had identical birth body weight, PR offspring body weight differed from control offspring around postnatal day 10 and remained lower until adulthood. Offspring glucose homeostasis was mildly impacted by maternal PR, although insulin secretion was reduced for PR rats at adulthood. Food intake, satiety response, and cerebral activation were examined after a lipid preload and demonstrated some differences between the two groups of rats. Maternal PR during gestation and lactation does induce extrauterine growth restriction, accompanied by alterations in maternal plasma leptin and adiponectin levels, which may be involved in programming the alterations in eating behaviour observed in females at adulthood.

6-gingerol ameliorates weight gain and insulin resistance in metabolic syndrome rats by regulating adipocytokines

Metabolic syndrome (MetS) can lead to increase of insulin resistance (IR) and visceral adipose tissue production of adipocytokines. 6-gingerol is known to have antioxidant and anti-inflammatory activities. Aim of this study is to investigate the effects of 6-gingerol on high-fat high-fructose (HFHF) diet-induced weight gain and IR in rats through modulation of adipocytokines. To induce MetS, male Sprague-Dawley rats were fed with a HFHF diet for 16 weeks and at Week 8, single-dose low-dose streptozotocin (22 mg/kg) were intraperitoneally injected. After 8 weeks of HFHF diet feeding, the rats were treated orally with 6-gingerol (50, 100, and 200 mg/kg/day) once daily for 8 weeks. At the end of the study, all animals were terminated, serum, liver, and visceral adipose tissues were harvested for biochemical analysis including the measurements of total cholesterol, triglycerides, HDL-cholesterol, fasting plasma glucose, insulin, leptin, adiponectin, proinflammatory cytokines (TNF-α and IL-6) and liver and adipose tissue histopathology. Biochemical parameters namely serum total cholesterol (243.7 ± 127.6 vs 72.6 ± 3 mg/dL), triglycerides (469.2 ± 164.9 vs 49.3 ± 6.3 mg/dL), fasting plasma glucose (334 ± 49.5 vs 121 ± 8.5 mg/dL), HOMA-IR (0.70 ± 0.24 vs 0.32 ± 0.06), and leptin (6.19 ± 1.24 vs 3.45 ± 0.33 ng/mL) were significantly enhanced, whereas HDL-cholesterol (26.2 ± 5.2 vs 27.9 ± 1.1 mg/dL) and adiponectin level (14.4 ± 5.5 vs 52.8 ± 10.7 ng/mL) were lowered in MetS vs normal control. Moreover, MetS were marked a significant increase in body weight and proinflammatory cytokines. Treatment with 6-gingerol dose-dependently restored all of those alterations towards normal values as well as the accumulation of lipid in liver and adipose tissues. These findings demonstrate that 6-gingerol, in a dose-dependent mode, showed capability of improving weight gain and IR in MetS rats through modulation of adipocytokines.

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

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

Longitudinal Trajectory and Early Life Determinant of Childhood Adipokines: Findings From a Racially Diverse Birth Cohort.

Leptin and adiponectin play important roles in systemic metabolic homeostasis, beginning in utero. Limited data exist on the levels and trajectories of these 2 hormones at birth and in childhood and their biological and social determinants. We examined the longitudinal trajectories of leptin and adiponectin from birth to early childhood, along with influential prenatal and infancy factors, and whether the trajectories and risk factors differ by preterm birth status. We included mother-infant pairs in the Boston Birth Cohort, a predominantly Black, indigenous, and people of color (BIPOC) study population. We measured infant plasma leptin and adiponectin levels at birth and in early childhood. We examined longitudinal trajectories and the associated prenatal maternal and infancy factors. We analyzed 716 infants (158 preterm) who had leptin and adiponectin measured at birth and in early childhood (mean corrected age 2.18 years [interquartile range, 0.4-10.4]). Cord leptin was higher in term infants (40 230 vs 20 481 in preterm, P < 0.0001) but childhood leptin did not differ by prematurity (4123 in term vs 4181 in preterm, P = 0.92). Adiponectin was higher in term infants at birth (18 416 vs 11 223, P < 0.0001) and in childhood (12 108 vs 10532, P = 0.04). In stepwise regression, Black race was associated with higher childhood leptin and lower childhood adiponectin. Female sex was associated with higher childhood leptin levels and lower childhood adiponectin levels in multivariable regression models. Our results highlight preterm status, race, and biological sex as predictors of adipokine trajectory throughout childhood. These findings raise the possibility that early life programming of adipokines may contribute to higher metabolic risk in life, especially among Black children born preterm.

OBESE MICE WITH PNEUMONIA HAVE HYPERLEPTINEMIA AND INCREASED PULMONARY SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 3 ACTIVATION.

Obesity is an ongoing epidemic that influences pathobiology in numerous disease states. Obesity is associated with increased plasma leptin levels, a hormone that activates the signal transducer and activator of transcription 3 (STAT3) pathway. Pneumonia is a significant cause of morbidity and mortality. During pneumonia, inflammatory pathways including STAT3 are activated. Outcomes in obese patients with pneumonia are mixed, with some studies showing obesity increases harm and others showing benefit. It is unclear whether obesity alters STAT3 activation during bacterial pneumonia and how this might impact outcomes from pneumonia. We used a murine model of obesity and pneumonia challenge with Pseudomonas aeruginosa in obese and nonobese mice to investigate the effect of obesity on STAT3 activation. We found obese mice with bacterial pneumonia had increased mortality compared with nonobese mice. Inflammatory markers, IL-6 and TNF-α, and lung neutrophil infiltration were elevated at 6 h after pneumonia in both nonobese and obese mice. Obese mice had greater lung injury compared with nonobese mice at 6 h after pneumonia. Leptin and insulin levels were higher in obese mice compared with nonobese mice, and obese mice with pneumonia had higher pulmonary STAT3 activation compared with nonobese mice.

Effects of the central melanocortin system on feed intake, metabolic hormones and insulin action in the sheep.

Voluntary feed intake is insufficient to meet the nutrient demands associated with late pregnancy in prolific ewes and early lactation in high-yielding dairy cows. Under these conditions, peripheral signals such as growth hormone and ceramides trigger adaptations aimed at preserving metabolic well-being. Recent work in rodents has shown that the central nervous system-melanocortin (CNS-MC) system, consisting of alpha-melanocyte-stimulating hormone (α-MSH) and agouti-related peptide (AGRP) acting respectively as agonist and antagonist on central MC receptors, contributes to the regulation of some of the same adaptations. To assess the effects of the CNC-MC on peripheral adaptations in ruminants, ewes were implanted with an intracerebroventricular cannula in the third ventricle and infused over days with artificial cerebrospinal fluid (aCSF), the α-MSH analog melanotan-I (MTI), or AGRP. Infusion of MTI at 0.03 nmol/h reduced intake, expressed as a fold of maintenance energy requirement (M), from 1.8 to 1.1 M (P < 0.0001), whereas AGRP at 0.3 nmol/h increased intake from 1.8 to 2.0 M (P < 0.01); these doses were used in all subsequent experiments. To assess the effect of MTI on plasma variables, sheep were fed ad libitum and infused with aCSF or MTI or pair-fed to MTI-treated sheep and infused with aCSF (aCSFPF). Feed intake of the MTI and aCSFPF groups was 40% lower than the aCSF group (P < 0.0001). MTI increased plasma triiodothyronine and thyroxine in an intake-independent manner (P < 0.05 or less) but was devoid of effects on plasma glucose, insulin, and cortisol. None of these variables were altered by AGRP infusion in sheep fed at a fixed intake of 1.6 M. To assess the effect of CNS-MC activation on insulin action, ewes were infused with aCSF or MTI over the last 3 d of a 14-d period when energy intake was limited to 0.3 M and studied under basal conditions and during hyperinsulinemic-euglycemic clamps. MTI had no effect on plasma glucose, plasma insulin, or glucose entry rate under basal conditions but blunted the ability of insulin to inhibit endogenous glucose production during hyperinsulinemic-euglycemic clamps (P < 0.0001). Finally, MTI tended to reduce plasma leptin in sheep fed at 0.3 M (P < 0.08), and this effect became significant at 0.6 M (P < 0.05); MTI had no effect on plasma adiponectin irrespective of feeding level. These data suggest a role for the CNC-MC in regulating metabolic efficiency and peripheral insulin action.

Exploration of plasma adiponectin, leptin, and COMT genotype on blood pressure among women who are post-menopause.

Research suggests that adiponectin, leptin, and genetic polymorphisms such as catechol-O-methyltransferase (COMT) genotype may play an integral role in blood pressure status and thereby cardiovascular health. This is an area especially important for women who are post-menopause; however, the current literature investigating these associations is limited. This study was a cross-sectional secondary analysis of baseline data (N 237) from the Minnesota Green Tea Trial (MGTT). The current study explored the relationships between plasma adiponectin, leptin, and COMT genotype on blood pressure measures. Plasma adiponectin and leptin were obtained after an overnight fast of at least 10 h and were measured by the radioimmunoassay method. The relationships were analysed using multiple linear regression after adjusting for potential confounders. Effect modifications by age, body mass index (BMI) category, blood pressure category, antihypertensive medication use, and COMT genotype were also investigated. The majority of participants were non-Hispanic (97⋅9%) and Caucasian (94⋅9%). Mean (sd) age and BMI were 60⋅7 (5⋅0) years and 28⋅2 (2⋅9) kg/m2, respectively. After adjustment for confounding variables, neither plasma adiponectin, plasma leptin nor COMT genotype was associated with systolic or diastolic blood pressure measures. The results of stratified analyses also did not reveal any significant interactions or associations. Based on the findings of this study, which utilised more rigorous statistical methods than previous research, neither adiponectin, leptin nor COMT genotype play a role in blood pressure measures in women who are post-menopause.

Intermittent Hypoxia and Weight Loss: Insights into the Etiology of the Sleep Apnea Phenotype.

Sleep apnea (SA) is a major respiratory disorder with increased risk for hypertension and obesity; however, our understanding of the origins of this complex disorder remains limited. Because apneas lead to recurrent drops in O2 during sleep, intermittent hypoxia (IH) is the main animal model to explore the pathophysiology of SA. Here, we assessed the impacts of IH on metabolic function and related signals. Adult male rats were exposed to 1week of moderate IH (FiO2=0.10-30s, ten cycles/hour, 8h/day). Using whole-body plethysmography, we measured respiratory variability and apnea index during sleep. Blood pressure and heart rate were measured by the tail-cuff method; blood samples were taken for multiplex assay. At rest, IH augmented arterial blood pressure, respiratory instability, but not apnea index. IH induced weight, fat, and fluid loss. IH also reduced food intake and plasma leptin, adrenocorticotropic hormone (ACTH), and testosterone levels but increased inflammatory cytokines. We conclude that IH does not replicate the metabolic clinical features of SA patient, thus raising our awareness of the limitations of the IH model. The fact that the risk for hypertension occurs before the appearance of apneas provides new insights into the progression of the disease.

OBSTETRIC AND PERINATAL ASPECTS OF METABOLIC DISORDERS IN PREGNANT WOMEN.

The aim: To determine the feasibility of using Tivortin in metabolic disorders during pregnancy and its effect on the course of pregnancy, childbirth, fetal and neonatal status. Materials and methods: We examined 210 pregnant women with metabolic disorders using clinical and laboratory data, uterine artery Doppler, determi¬nation of lipid peroxidation and antioxidant system, leptin and placental growth factor content. The fetal condition was assessed by ultrasound examination with Doppler, determination of biophysical profile, and cardiotocography. Results: Metabolic disorders in pregnant women increase the risk of obstetric and perinatal complications by activating lipid peroxidation and inhibiting the antioxidant system, reducing the content of placental growth factor and increasing the level of leptin in the blood plasma. After treatment, there was a significant decrease in leptin levels and an increase in placental growth factor levels, normalization of lipid peroxidation and antioxidant system, uterine artery pulsatility index and umbilical cord peak systolic velocity index, systolic-diastolic ratio, fetal biophysical profile and cardiotocography. The incidence of complications in childbirth decreased by 3 times, surgical interventions - by 2 times, postpartum infectious complications - by 1.7 times, and the birth of infants in a state of asphyxia - by 1.8 times. Conclusions: Metabolic disorders in pregnant women are a significant factor in the development of obstetric and perinatal complications due to the intensity of lipid peroxidation and depression of the antioxidant system, and a decrease in the content of placental growth factor. The use of Tivortin in the treatment of pregnant women with metabolic disorders has proven its safety and efficacy.

Serum leptin levels in patients with chronic kidney disease and hypertensive heart disease: An observational cross-sectional study.

Adipocytes secrete a peptide hormone called leptin, which plays a crucial role in controlling appetite and energy expenditure. Alterations in leptin concentrations are associated with CKD-related cardiovascular problems such as hypertensive heart disease (HHD). Despite the link, data on the precise function of leptin in people with CKD and HHD is scant. An observational cross-sectional study involving a total of 108 participants (72 CKD patients with HHD and 36 healthy controls). Their demographic and anthropometric information was collected using a standardized questionnaire. Certain clinical measures such as blood pressure and body mass index (BMI) were assessed. Fasting blood samples were analyzed for levels of plasma glucose (FPG), lipids, creatinine, and leptin. Data were analyzed with SPSS v23. Leptin, FPG, creatinine and triglyceride levels were all significantly higher in CKD patients with HHD compared to controls (p < 0.01 for all). Furthermore, advanced CKD status (being in stage 5), having a 6-year diagnosis of HHD, being female, having a higher BMI, and elevation in levels of HDL and FPG contributed significantly to the variance in serum leptin levels in the case group (β = 0.37, 0.22, 0.19, 0.18, 0.27, 0.28; p < 0.05 for all). In the control group, the female gender had the biggest unique effect on circulating leptin levels, followed by BMI and eGFR (β = 0.71, 0.34, -0.22; p < 0.01 for all). Patients with CKD who also had HHD reported considerably higher circulating leptin levels. Significantly higher blood leptin levels were shown to be associated with CKD stage 5 in the case group. These results are consistent with the role of leptin in the metabolic complexity seen in CKD patients. There needs to be more research into treatments that aim to lower leptin levels in CKD patients with HHD.

Goishi tea leaf powder affects lower body weight and visceral fat accumulation during energy restriction in obese rats.

Goishi tea is a unique Japanese post-fermented tea produced in Kochi prefecture. The aim of this study was to investigate whether the supplementation of energy-restricted diet with Goishi tea leaves affects body weight, visceral fat accumulation, and fecal lipids in diet-induced obese rats. 18 male Wistar rats were fed a high-fat diet for 12 weeks. Subsequently, the diet-induced obese rats were fed a low-energy diet containing 1% (G1 group) or 3% (G3 group) of Goishi tea leaf powder, or without any tea extracts (C group) for 4 weeks. After 4 weeks, body weight and body fat ratio were significantly lower in the G3 group than in the C group. Plasma insulin levels were significantly higher in the C group than in the G1 and G3 groups, whereas plasma leptin levels were significantly lower in the G3 group than in the C group. In addition, the lipid absorption rate was significantly lower in the G3 group than in the C and G1 groups. In conclusion, the administration of Goishi tea leaves under dietary restrictions might contribute to body weight reduction and inhibition of lipid absorption, as a diet therapy to help prevent obesity and metabolic syndrome. J. Med. Invest. 70 : 60-65, February, 2023.

PS-B03-8: ORAL CANNABIDIOL REDUCES ARTERIAL BLOOD PRESSURE DURING EARLY PHASE METABOLIC SYNDROME IN OLETF RATS

Objective: Cardiovascular disease (CVD) is the leading cause of death in the U.S. and a primary outcome of metabolic syndrome (MetS). MetS is diagnosed by the presentation of at least 3 of the 6 conditions including abdominal obesity, elevated arterial pressure, and glucose intolerance ± insulin resistance. Identifying the root cause of these conditions individually is difficult but developing new treatments, which can ameliorate the multiple conditions of MetS has greater potential to reduce later-onset CVD. The benefits of cannabidiol (CBD) is widely recognized for potent anti-inflammatory and antioxidative properties, which may be cardioprotective during isolated risk factor conditions. However, these effects have not been examined during MetS conditions. Design: A cohort of 14-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats were administered 175 mg CBD/kg by oral gavage for 5 weeks (CBD; n = 8). Animals were fed ad libitum and monitored alongside vehicle-treated OLETF (OLETF; n = 8) and vehicle-treated Long-Evans Tokushima Otsuka (LETO) rats, the lean-strain controls (LETO; n = 8). Rats were implanted with biotelemeters to chronically measure arterial pressure [DSI; HD-S10]. An oral glucose tolerance test (oGTT) was performed after 5 weeks of treatment. Results: CBD reduced arterial pressure within the first week of dosing (6 ± 1.4 mmHg or 4.1%; p &lt; 0.05) and, after 5 weeks, by 9.7 ± 1.7 mmHg (6.5%; p &lt; 0.05) from baseline. CBD blunted body mass gain and reduced abdominal adiposity by 39% (p &lt; 0.0001) compared to untreated OLETF. Additionally, glucose absorption (AUCglucose 10 minutes after glucose bolus) was reduced 21% (p &lt; 0.01) and enhanced uptake (slope 60 minutes to 120 minutes after glucose bolus) by 160% (p &lt; 0.05). However, neither glucose response overall nor static fasting blood glucose were improved. On the other hand, insulin response (AUCinsulin) was reduced 77% (p &lt; 0.0001) compared to OLETF, which ultimately reduced calculated insulin resistance index (IRI) of 79% (p &lt; 0.0001). Moreover, CBD treatment reduced fasting plasma insulin by 76% compared to OLETF (p &lt; 0.001). CBD decreased adiposity by 59% (p &lt; 0.0001) associated with reduced plasma leptin. Conclusions: A chronic, high dose of CBD reduced the MetS-associated hypertension and other cluster factors. The renin-angiotensin-aldosterone system is a known driver of hypertension in humans with MetS and in the OLETF rat model and could be directly or indirectly modulated by CBD (analysis on-going). Collectively, CBD could be a novel and effective intervention strategy for early-stage hypertension and other metabolic risk factors associated with MetS.

Circulating leptin levels in the assessment of Crohn's disease activity and its relation to nutritional status.

Objective: to evaluate leptin levels and its relation to nutritional status in Crohn's disease (CD). Methods: the study included 154 CD patients and healthy controls. Leptin level was determined before treatment. Nutrition levels were assessed using the Nutrition Risk Screening 2002 (NRS-2002) and Patient-Generated Subjective Global Assessment (PG-SGA). Indicators included body mass index (BMI), mid-arm circumference, the circumference of the upper-arm muscle, triceps skinfold thickness, and circumference of legs. Results: leptin levels differed between CD patients (1,025 ± 874 ng/ml) and controls (18,481,222 ng/ml). Significant differences were seen in NRS-2002, PG-SGA scores, BMI and other nutritional indicators. Negative correlations were observed between leptin and NRS-2002, PG-SGA scores, while positive correlations were observed with other nutritional indicators. The receiver operating characteristic (ROC) curve showed association between leptin and the diagnosis of CD, suggesting leptin concentration below 803.02 ng/ml as a threshold for CD. Conclusion: dysfunctional leptin regulation may relate to poor nutritional status associated with CD. The leptin level is thus an additional tool for evaluating CD patients, predicting disease activity and clinical response. Leptin may be a potential target for intervention in CD to improve nutritional status.

A Case-Control Study of the Association of Leptin Gene Polymorphisms with Plasma Leptin Levels and Obesity in the Kerala Population.

Over the last few years, the importance of leptin in energy metabolism has been extensively studied in both animal models and in humans. Very few results are available on the association between human leptin gene (LEP) variants and obesity traits in India. We designed this study to analyse the polymorphisms in human leptin gene and the association of sequence variants with obesity among the population in Kerala, South India. In this case-control design of 148 study participants, data were collected on socioeconomic aspects and anthropometric measurements. Plasma glucose, insulin, leptin, and lipid profile were measured. Genotyping was done by automated DNA sequencing. The common Single Nucleotide Polymorphism (SNP) of 5'-UTR of LEP - 2548G/A was found to be present in the study population with "A" variant as dominant allele. A novel synonymous mutation Thr5Thr of exon 2 of LEP was identified in heterozygous form in one subject with morbid obesity with hyperleptinemia. A novel missense mutation Phe17Leu was observed in two subjects with obesity in heterozygous condition. A novel missense mutation Lys36Arg in exon 2 of LEP was observed in one subject with abdominal obesity and decreased serum leptin level. LEP - 2548G/A at 5'-untranslated region was found to be common with the mutant "A" variant in the study population. SNPs of exons in LEP were found to be rare but associated with morbid obesity and altered levels of serum leptin in the study population in Kerala, India.

Egg Introduction during Infancy is Associated with Lower Fat Mass Index in Females at Early Adolescence

BackgroundEgg consumption may play an important role in early-life growth given their high-quality protein, essential fatty acids, and micronutrients. ObjectivesStudy objectives were to examine the longitudinal associations of infant age at egg introduction with obesity outcomes in early childhood, middle childhood (mid-childhood), and early adolescence. MethodsWe used existing data from 1089 mother-child dyads from Project Viva to estimate age at egg introduction through a questionnaire completed by mothers at ∼1 y postpartum (mean ± SD, 13.3 ± 1.2 mo). Outcome measures included height and weight (early childhood, mid-childhood, and early adolescence), body composition including total fat mass, trunk fat mass, and lean mass (mid-childhood and early adolescence), and plasma adiponectin and leptin (early and mid-childhood and early adolescence). We defined childhood obesity as sex- and age-specific BMI ≥ 95th percentile. We estimated the associations of infant age at egg introduction with risk of obesity using multivariable logistic regression and multivariable linear regression models for BMI-z-score, body composition measures, and adiposity hormones; adjusted for maternal prepregnancy BMI and sociodemographics. ResultsAmong females, those introduced to egg by the 1-y survey had a lower total fat mass index (confounder-adjusted mean difference, −1.23 kg/m2; 95% CI: −2.14, −0.31), and trunk fat mass index (confounder-adjusted mean difference, −0.57 kg/m2; 95% CI: −1.01, −0.12) in early adolescence compared to those not introduced (reference group). However, no associations between infant age at egg introduction and risk of obesity were observed among males (confounder-adjusted odd ratio [aOR], 1.97; 95% CI: 0.90, 4.30) or females (aOR, 0.68; 95% CI: 0.38, 1.24) across all ages. Egg introduction in infancy was associated with lower plasma adiponectin among females (confounder-adjusted mean difference, −1.93 μg/mL; 95% CI: −3.70, −0.16) in early childhood only. ConclusionsEgg introduction during infancy among females is associated with lower total fat mass index in early adolescence and plasma adiponectin in early childhood. This trial was registered at clinicaltrials.gov as NCT02820402.

Associations of leptin and corticostriatal connectivity in bipolar disorder

Bipolar disorder (BD) and metabolic disturbance represent a chronic state of low-grade inflammation and corticostriatal circuitry alterations. Herein, we aimed to investigate whether plasma leptin, an adipokine that plays a key role in the interplay of metabolism and inflammation, is associated with corticostriatal connectivity in patients with BD. Twenty-eight BD I patients, 36 BD II patients and 66 healthy controls were enrolled and completed the Hamilton Depression Rating Scale, the Young Mania Rating Scale, and the Recent Life Change Questionnaire. Fasting plasma leptin and C-reactive protein (CRP) levels were measured, and corticostriatal connectivity was examined using functional magnetic resonance imaging (fMRI). The relationships between leptin, CRP and body mass index (BMI) identified in the controls and BD II patients were absent in the BD I patients. We did not find a significant group difference in the leptin level; nevertheless, the negative correlation between leptin level and corticostriatal connectivity (ventrolateral prefrontal cortex and inferior temporal gyrus) observed in the healthy controls was absent in the BD patients. The disproportionate increase in leptin level with increasing BMI in BD indicated a potential inflammatory role of white adipose tissue in BD. Furthermore, higher CRP levels in BD I patients might induce leptin resistance. Collectively, our results implied vulnerability to inflammatory and metabolic diseases in patients with BD, especially BD I.

Artemisiae argyi Water Extract Alleviates Obesity-Induced Metabolic Disorder.

Artemisiae argyi is a well-known traditional herbal medicine used in East Asia. Although the antibacterial and anti-inflammatory effects of A. argyi have been reported, its efficacy in improving obesity has not been yet evaluated. In this study, mice were fed a normal diet (AIN-93), a high-fat diet (HFD, 60% of kcal from fat), and an HFD with 0.1% of A. argyi water extract for 16 weeks. The body weight and body fat in A. argyi-fed mice significantly decreased via upregulation of the mRNA expression of fatty acid oxidation-related genes, with a simultaneous decrease in plasma lipid content and leptin levels. A. argyi water extract also ameliorated hepatic steatosis by restricting lipogenesis via lowering the activities of fatty acid synthase and phosphatidic acid phosphatase. Consistently, hepatic histological analysis indicated that A. argyi water extract decreased hepatic lipid accumulation in accordance with the hepatic H, E and Oil Red O-stained area. Additionally, A. argyi ameliorated the impaired glucose homeostasis by increasing the mRNA expression of AMP-activated kinase and glycolysis-related genes. In conclusion, our results indicate that A. argyi can be used to treat obesity-related metabolic conditions.