Leptin receptor deficiency impedes metabolic surgery related-weight loss through inhibition of energy expenditure in db/db mice.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) surgery is an effective metabolic surgery against diabetes and obesity. Clinical evidence indicates that patients with severe obesity have a poor curative effect in losing weight if they suffer from leptin or its receptor deficiency, but the underlying mechanism remains elusive. Here, we investigated the effect of leptin receptor deficiency on metabolic dysfunction in db/db mice treated by RYGB surgery. METHODS: The db/db mice and their heterozygote control db/m mice were subjected to RYGB or sham surgery. Body weight, blood glucose, food intake and glucose tolerance were evaluated. Micro-PET/CT and histological analysis were performed to examine the glucose uptake of tissues and the fat changes in mice. The key factors in glucose and fatty acid metabolism were detected by western blot analysis. RESULTS: Compared with the sham group, the db/db mice in the RYGB group showed more significant weight regain after surgical recovery and improvement in hyperinsulinemia and glucose tolerance. However, the total body fat and multiple organ lipid deposition of RYGB-treated db/db mice was increased. The underlying mechanism studies suggested that the activation of AMPK regulated GLUT4 to increase glucose uptake, but AMPK could not promote fatty acid oxidation through the JAK2/STAT3 pathway under leptin receptor deficiency in db/db mice. CONCLUSION: We conclude that leptin receptor deficiency impedes the AMPK activation-mediated fat catabolism but does not affect AMPK-related glucose utilization after metabolic surgery in db/db mice. This result helps select surgical indications for patients with obesity and diabetes.

Safety assessment of the SGLT2 inhibitors empagliflozin, dapagliflozin and canagliflozin during pregnancy: An ex vivo human placenta perfusion and in vitro study.

Although uncontrolled hyperglycaemia during pregnancy can cause complications for both the mother and her offspring, pharmacological treatment options for gestational and type 2 diabetes in pregnancy are still limited. Empagliflozin (EMPA), dapagliflozin (DAPA) and canagliflozin (CANA) are three sodium glucose co-transporter 2 (SGLT2) inhibitors, a newer group of oral antidiabetics that are well established in the treatment of type 2 diabetes mellitus in non-pregnant patients. To date, no data regarding their placental transfer and safety in pregnant women are available. We performed ex vivo human placental perfusions (n = 4, term placentas, creatinine and antipyrine as connectivity controls) to evaluate the transplacental transfer of EMPA, DAPA and CANA across the placental barrier and assessed their influence on the secretion of two placental peptide hormones, leptin and ß-human chorionic gonadotropin (ß-hCG). We discovered that all three SGLT2 inhibitors cross the placental barrier and attained maximal foetal to maternal concentration ratios of 0.38 ± 0.09 (EMPA), 0.67 ± 0.05 (DAPA) and 0.62 ± 0.05 (CANA) within the tested 360 min. A moderate but statistically significant decrease in placental leptin - but not ß-hCG - secretion was observed during perfusions with SGLT2 inhibitors, which was confirmed in experiments performed with human placental BeWo cells. SGLT2 inhibitors are able to cross the human placental barrier and seem to interfere with placental leptin production. These observations should be considered in the ongoing discussion on the optimal treatment for gestational diabetes and type 2 diabetes mellitus in pregnancy.

Leptin and energy balance: exploring Leptin's role in the regulation of energy intake and energy expenditure.

Leptin is a tonic appetite-regulating hormone, which is integral for the long-term regulation of energy balance. The current evidence suggests that the typical orexigenic or anorexigenic response of many of these appetite-regulating hormones, most notably ghrelin and cholecystokinin (CCK), require leptin to function whereas glucagon-like peptide-1 (GLP-1) is required for leptin to function, and these responses are altered when leptin injection or gene therapy is administered in combination with these same hormones or respective agonists. The appetite-regulatory pathway is complex, thus peptide tyrosine tyrosine (PYY), brain-derived neurotrophic factor (BDNF), orexin-A (OXA), and amylin also maintain ties to leptin, however these are less well understood. While reviews to date have focused on the existing relationships between leptin and the various neuropeptide modulators of appetite within the central nervous system (CNS) or it's role in thermogenesis, no review paper has synthesised the information regarding the interactions between appetite-regulating hormones and how leptin as a chronic regulator of energy balance can influence the acute appetite-regulatory response. Current evidence suggests that potential relationships exist between leptin and the circulating peripheral appetite hormones ghrelin, GLP-1, CCK, OXA and amylin to exhibit either synergistic or opposing effects on appetite inhibition. Though more research is warranted, leptin appears to be integral in both energy intake and energy expenditure. More specifically, functional leptin receptors appear to play an essential role in these processes.

Assessment of Leptin Levels and Their Correlation With the Severity of Obstructive Sleep Apnea Syndrome: A Case-Control Study.

Background Obstructive sleep apnea (OSA) is characterized by a combination of structural issues in the upper airway and imbalances in the respiratory control system. While numerous studies have linked OSA with obesity, it remains uncertain whether leptin, a hormone associated with fat, plays a role in the functional and anatomical defects that lead to OSA. Therefore, the aim of this study was to investigate whether leptin levels could be used as a predictor of OSA syndrome (OSAS). Methodology A case-control observational study was conducted, enrolling study participants who reported obesity (BMI > 30) within the range of >30 to <35 kg/m2, along with a short neck and a history of snoring, excessive daytime drowsiness, fatigue, or insomnia. Leptin levels and fasting blood sugar (FBS) were measured in all individuals. Additionally, the study evaluated the severity of OSAS using indicators such as the STOP BANG scores, apnea-hypopnea index, uvula grade score, and Epworth Sleepiness Scale scores. Results A total of 80 participants (40 cases and 40 controls) were included in the study. The mean leptin and FBS levels were significantly higher in cases compared to controls. Moreover, leptin levels exhibited a significant correlation with the severity indices of OSAS. Conclusion The study findings indicate that individuals with higher leptin levels tend to exhibit more severe OSAS symptoms. Furthermore, these elevated leptin levels contribute to the worsening of various OSA symptoms. Larger controlled studies have suggested that pharmacologically restoring the altered leptin levels may serve as a beneficial adjunct to treatment for alleviating OSAS symptoms.

Energy expenditure in myelofibrosis patients treated with a JAK1/2 inhibitor.

Weight gain is a known adverse effect of ruxolitinib, a JAK1/2 inhibitor that is the mainstay of treatment for many patients with myelofibrosis. The mechanisms behind weight increase with ruxolitinib is incompletely understood, although decreased adipose tissue lipolysis and increased appetite due to blocking the effects of leptin in the hypothalamus have been proposed. In order to explore the metabolic changes in ruxolitinib-treated patients with myelofibrosis, we performed a pilot study to assess the feasibility of using a portable indirect calorimeter to quantify energy expenditure before and during ruxolitinib treatment and report the results of two patients. Waist circumference increased during ruxolitinib treatment in both patients. Energy expenditure initially increased followed by a decrease and then increase again, but to levels below baseline. These results suggest that weight gain secondary to ruxolitinib may be related to changes in whole body energy expenditure.

Assessment of the Role of Leptin and Adiponectinas Biomarkers in Pancreatic Neuroendocrine Neoplasms.

Data on the possible connection between circulating adipokines and PanNENs are limited. This novel study aimed to assess the serum levels of leptin and adiponectin and their ratio in patients with PanNENs and to evaluate the possible relationship between them and PanNEN's grade or stage, including the presence of metastases. The study group consisted of PanNENs (n = 83), and healthy controls (n = 39). Leptin and adiponectin measurement by an ELISA assay was undertaken in the entire cohort. The serum concentration of adiponectin was significantly higher in the control group compared to the study group (p < 0.001). The concentration of leptin and adiponectin was significantly higher in females than in males (p < 0.01). Anincreased leptin-adiponectin ratio was observed in well-differentiated PanNENs (G1) vs. moderatelydifferentiated PanNENs (G2) (p < 0.05). An increased leptin-adiponectin ratio was found in PanNENs with Ki-67 < 3% vs. Ki-67 ≥ 3% (p < 0.05). PanNENs with distal disease presented lower leptin levels (p < 0.001) and a decreased leptin-adiponectin ratio (p < 0.01) compared with the localized disease group. Leptin, adiponectin, and the leptin-adiponectin ratio may serve as potential diagnostic, prognostic, and predictive biomarkers for PanNENs. Leptin levels and the leptin-adiponectin ratio may play an important role as predictors of malignancy and metastasis in PanNENs.

Subjective assessment and biochemical evaluation of traction therapy in women with chronic low back pain: does body mass index matter? A clinical study.

BACKGROUND: Apart from the positive effect of lumbar traction on structural changes within the spine in patients with low back pain, it is likely that therapeutic effects are correlated with pain biomarkers in the blood. Among them, systemic metabolic factors related to obesity may play an important role. This is the first study designed to examine the effectiveness of traction therapy in two experimental groups with considerably different BMI and to assess relationships between blood biomarkers and low back pain intensity. METHODS: In the prospective clinical trial, women suffering from chronic low back pain were allocated into the normal-weight or obesity groups. Patients in both groups underwent twenty sessions of lumbar traction therapy (30 min a day, continuous mode with a force level of 25-30% of body weight). Before and after therapy subjective assessments of pain (VAS and PPT) were performed, and serum concentrations of aggrecan chondroitin sulfate 846 epitope (CS-846), neuropeptide Y, leptin, adipsin and growth and differentiation factor 15 (GDF-15) were determined. The data were statistically evaluated for 28 women. RESULTS: After therapy, the maximal low back pain decreased in both groups, GDF-15 concentration was reduced in the normal-weight group and increased in the obesity group, and CS-846 concentration decreased in the obesity group. The sensation of PPT in the lumbar spine and mean concentrations of neuropeptide Y, leptin and adipsin did not change in both groups. However, the relationships of GDF-15, leptin, and adipsin concentrations with the perception of pain were revealed. CONCLUSION: Distinct differences between the normal-weight and obesity groups pointed on the role of excessive adipose tissue in aggravating the inflammatory processes and in the development of low back pain. Adipsin, CS-846 and GDF-15 aspire to be the low back pain biomarkers in women with obesity, but there is a need for further research to answer whether they might be considered reliable biomarkers for the prognosis and monitoring of chronic low back treatment. TRIAL REGISTRATION: NCT04507074, registered prospectively on July 6, 2020.

Associations between Cord Blood Leptin Levels and Childhood Adiposity Differ by Sex and Age at Adiposity Assessment.

Lower cord blood leptin levels have been associated with lower and higher adiposity in childhood and associations seem to differ according to the child's age, methods of adiposity assessment and sex. Our aim was to investigate sex-specific associations of cord blood leptinemia with childhood adiposity at birth, 3 and 5 years of age. We measured cord blood leptin using Luminex immunoassays in 520 offspring from the Gen3G cohort. We tested associations between cord blood leptin and body mass index (BMI) z-score, skinfolds thicknesses (SFT), and body composition using dual-energy X-ray absorptiometry, adjusted for confounders. At birth, girls had almost twice as much leptin in cord blood as boys (15.5 [8.9; 25.6] vs. 8.6 [4.9; 15.0] ng/mL; p < 0.0001) as well as significantly greater adiposity. Lower levels of cord blood leptin were associated with higher sum of SFT (ß = −0.05 ± 0.02; p = 0.03) and higher BMI z-score (ß= −0.22 ± 0.08; p = 0.01) in 3-year-old boys only. We did not observe these associations at age 5, or in girls. Our results suggest a sexual dimorphism in the programming of leptin sensitivity and childhood adiposity, but further observational and functional studies are needed to better understand the role of leptin in early life.

Assessment of vitamin D levels and adipokines mediated obesity among psychiatric patients on treatment and treatment naïve: A comparative cross-sectional study.

Background and aims: Antipsychotic treatment may contribute to low vitamin D levels and have impact on direct anti-inflammatory activity such as adiponectin activity and indirect proinflammatory activity such as leptin and resistin activity. However, vitamin D levels and adipokines mediated effect on weight gain and increased adiposity are not well evaluated. This study, therefore, assessed vitamin D and adipokines-mediated obesity among Ghanaian psychiatric patients. Methods: This comparative cross-sectional study was conducted at psychiatric unit of Komfo Anokye Teaching Hospital, Kumasi, Ghana. Anthropometric measurements, sociodemographic and previous medical history were taken from 300 antipsychotics treatment naïve and active patients. Obesity was classified using World Health Organization (WHO) body mass index (BMI)-specific cut-offs. Blood samples were collected for serum vitamin D and adipokines (adiponectin, leptin, and resistin) analysis using enzyme-linked immunosorbent assay. Statistical analyses were done using SPSS version 26.0 and GraphPad Prism version 8.0. Results: We observed higher prevalence of obesity among treatment active psychiatric patients (40.7%) compared to treatment naïve group (16.8%). Vitamin D insufficiency and deficiency prevalence were significantly higher among the treatment active group (25.3%; 39.5%; p < 0.001) and associated with increased odds of obesity (91.8%; cOR = 91.84, 95% confidence interval [CI]: 24.94-338.13). Moreover, adiponectin (84.2%: cOR = 14.15, 95% CI: 5.52-36.27), leptin (55.6% cOR = 2.20, 95% CI: 1.04-4.67), and resistin (79.4%: cOR = -8.34, 95% CI: 3.39-20.55) were significantly associated with increased odds of obesity among treatment active psychiatric. Furthermore, treatment active psychiatric patients exhibited inverse correlation for adiponectin and leptin with BMI (r = -0.62; -0.24), and WHtR (r = -0.53; -0.24); however, a moderate positive correlation for resistin with BMI (r = 0.80), HC (r = 0.67), and WHtR (r = 0.65). Conclusion: Obesity is more prevalent in psychiatric patients on antipsychotics such as Olanzapine and Clozapine. Obesity among treatment active psychiatric patients is associated with vitamin D insufficiency and deficiency, low adiponectin and leptin levels but higher resistin level.

Late isocaloric eating increases hunger, decreases energy expenditure, and modifies metabolic pathways in adults with overweight and obesity.

Late eating has been linked to obesity risk. It is unclear whether this is caused by changes in hunger and appetite, energy expenditure, or both, and whether molecular pathways in adipose tissues are involved. Therefore, we conducted a randomized, controlled, crossover trial (ClinicalTrials.gov NCT02298790) to determine the effects of late versus early eating while rigorously controlling for nutrient intake, physical activity, sleep, and light exposure. Late eating increased hunger (p < 0.0001) and altered appetite-regulating hormones, increasing waketime and 24-h ghrelin:leptin ratio (p < 0.0001 and p = 0.006, respectively). Furthermore, late eating decreased waketime energy expenditure (p = 0.002) and 24-h core body temperature (p = 0.019). Adipose tissue gene expression analyses showed that late eating altered pathways involved in lipid metabolism, e.g., p38 MAPK signaling, TGF-ß signaling, modulation of receptor tyrosine kinases, and autophagy, in a direction consistent with decreased lipolysis/increased adipogenesis. These findings show converging mechanisms by which late eating may result in positive energy balance and increased obesity risk.

Immunohistochemical identification and assessment of the location of leptin, visfatin and chemerin in the liver of men with different body mass index.

BACKGROUND: Adipokines such as leptin, visfatin and chemerin play a pivotal role not only in the pathogenesis of excessive weight gain but also impact on hepatic metabolism. However, alterations in the production of these peptides in the liver of overweight individuals have not been fully elucidated yet. The aim of the study was to evaluate changes in leptin, visfatin and chemerin biosynthesis in the liver of men with different BMI. METHODS: Fourteen adult men without symptoms from the digestive system were recruited. Research material consisted of liver samples. Study participants were divided into two groups: lean (BMI ≤ 25 kg/m2) and overweight subjects (BMI > 25 kg/m2). Paraffin liver sections were processed by immunohistochemistry for detection of leptin, visfatin and chemerin. Hepatic expression of leptin, visfatin and chemerin genes was determined by qRT-PCR method. RESULTS: Increased immunoreactivity for leptin and chemerin, and decreased immunoreaction for visfatin were observed in the liver of overweight men in comparison to lean subjects. Overweight subjects with hepatic steatosis displayed increased immunoreactivity for leptin and weaker immunoreaction against visfatin and chemerin in the liver, compared to individuals with normal organ structure. Expression of leptin and chemerin was enhanced in the liver of overweight individuals, with the highest expression observed in subjects with hepatic steatosis. Conversely, expression of visfatin in the male liver was decreased in overweight subjects and those with and liver steatosis. CONCLUSIONS: The present study proves that the expression of leptin, visfatin and chemerin in the male liver is altered in overweight individuals. Our report also indicates the potential importance of these peptides in hepatic steatosis associated with overweight.

Association of Serum Adipokines and Resting Energy Expenditure in Patients With Chronic Kidney Disease.

Background and Aim: Metabolic disorders are prevalent in patients with chronic kidney disease (CKD) and may lead to protein energy wasting (PEW). Adipokines improve connections between PEW and energy metabolism. We aimed to determine the relationship between adipokine levels and resting energy expenditure (REE) in patients with CKD. Methods: A total of 208 patients in non-dialyzed CKD stages 3-5 were enrolled in this cross-sectional study. Serum adipokines (leptin, adiponectin, and interleukin 6 (IL-6) were measured using enzyme-linked immunosorbent assay. Patient's REE was measured using indirect calorimetry. Fat mass (FM) and lean tissue mass (LTM) were measured using multiple-frequency bioimpedance analysis. Spearman correlation analyses and multivariate linear regression models were used to assess the association between serum adipokines and REE. Results: The mean age was 52.7 ± 14.6 years, and 26.9, 26.4, and 46.7% of our participants had CKD stages 3, 4, and 5, respectively. The median values of serum adiponectin, leptin, and IL-6 were 470.4 (range, 291.1-802.2), 238.1 (range, 187.9-418.4), and 4.0 (range, 2.4-9.5) pg/mL, respectively. The male participants had significantly lower FM% (P = 0.001) and lower leptin levels (P < 0.001) than the female participants. After adjusting for age, diabetes, high-sensitivity C-reactive protein, intact parathyroid hormone, LTM, and FM, multiple linear regression analysis revealed that serum leptin levels were significantly positively associated with REE in men rather than in women (P < 0.05). Serum adiponectin levels were inversely associated with REE in men, but this association disappeared while FM was additionally adjusted. Adiponectin levels in women were not correlated with REE (P > 0.05). IL-6 was not significantly associated with REE in either men or women. Conclusions: A sex-specific relationship between serum adipokines (leptin and adiponectin) and REE was observed in patients with CKD stages 3-5, which was partly confounded by FM.

Combination of Endogenous Estradiol and Adipokine Leptin in Breast Cancer Risk and Prognosis Assessment in Postmenopausal Chinese Women.

Objective: Our study aims to clarify the role of estradiol and leptin in breast cancer risk and prognostic assessment in postmenopausal Chinese women. Design: The serum circulating estradiol and leptin level was detected by ELISA. Then the correlation between estradiol, leptin level, and clinical characteristics was analyzed using Fisher's exact test. Next, the Kaplan-Meier model was used to analyze the association between estradiol, leptin, and prognosis of postmenopausal breast cancer patients in our cohort and the TCGA dataset. Setting: The study was conducted at the National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College. Patients: A total of 182 postmenopausal breast cancer patients and 111 healthy subjects from January 2010 to August 2010 were included in the analysis. Another 702 cases with breast cancer were retrieved from The Cancer Genome Atlas (TCGA) database for subsequent analysis. Main Outcome Measure: Serum circulating estradiol and leptin level. Results: The level of estradiol was significantly higher (P<0.001) but the level of leptin had no significant difference (P = 0.764) in postmenopausal breast cancer patients compared with healthy subjects. The level of estradiol and leptin was not significantly different between estrogen receptor (ER) positive and ER-negative groups (P>0.05). Estradiol was significantly correlated with tumor T stage (P = 0.002) and leptin was significantly associated with perineural invasion (P = 0.014). In addition, the disease-free survival of patients with a high level of estradiol was significantly shorter (P = 0.025) but leptin tended to be a protective factor for overall survival in TCGA analysis (P = 0.038). Conclusion: Circulating estradiol and leptin played important roles in the risk of postmenopausal breast cancer even in low-estrogen nations with an independent expression of ER status. High circulating estradiol was a poor prognostic factor and leptin may be a protection signal in Chinese postmenopausal patients with breast cancer.

[Pathogenetic mechanisms for the development of hematological disorders in induced fatty liver disease in Wistar rats and assessment of the regulatory effects of carnosine and α-lipoic acid].

The study of the relationship between hematopoiesis and metabolism is now particularly relevant in view of the high incidence of alimentary dependent diseases, including non-alcoholic fatty liver disease. In this regard, pathogenetic factors of this disease development are studied actively in order to choose adequate drug therapy and usage of bioactive substances with antioxidant properties. The aim of the study was to study the pathogenetic relationship of hematological disorders and imbalance of growth factors, leptin and ghrelin in male Wistar rats in the model of the initial stage of non-alcoholic fatty liver disease development and to assess the regulatory effect of minor bioactive substances - carnosine and α-lipoic acid. Material and methods. The studies were performed on male Wistar rats with initial body weight 150±10 g within 8 weeks. Animals were divided into 5 groups (n=8 in each). Rats of the control group received a complete modified diet AIN93M, in which soybean oil was replaced with sunflower oil and lard (1:1). Rats of the experimental groups consumed high-calorie choline-deficient diet (HCCDD), in which fat content was 45%, fructose content - 20% of the energy value of the diet. Rats of the 2nd group were fed HCCDD without any supplements, the 3rd group - with the addition of carnosine (75 mg/kg body weight), the 4th group - with the addition of α-lipoic acid (75 mg/kg body weight), the 5th group - with the combined addition of carnosine and α-lipoic acid in a total dose of 150 mg/kg body weight. Hematological values were determined on a hematological analyzer. The content of ghrelin and leptin, as well as growth factors GM-CSF and M-CSF in blood plasma and adipose tissue lysates, was determined by multiplex immunoassay using xMAP technology. Results. Rat intake of HCCDD resulted in decreased hemoglobin levels and red blood cell scores compared to controls. Diet enrichment with carnosine and α-lipoic acid did not have a reliable effect on these indicators. Carnosine intake had a protective effect on erythrocyte volume, a decrease of which was recorded in other experimental groups. HCCDD stimulated the growth of the absolute number of leukocytes in peripheral blood due to granulocytes and mononuclears. The enrichment of HCCDD with carnosine and α-lipoic acid led to a further increase in leukocytosis, the maximum level of which was observed in the group of rats fed HCCDD, simultaneously enriched with carnosine and α-lipoic acid (14.86±1.48×109/l compared to 8.67±1.23×109/l in control). All diets used in the research had no effect on the number of erythrocytes and platelets in the peripheral blood of rats. The use of both HCCDD alone and in combination with carnosine or α-lipoic acid intake had a negative effect on the level of growth factors GM-CSF and M-CSF in blood plasma and adipose tissue. The consumption of HCCDD caused an increase in leptin blood level (8.54±0.69 compared to 2.58±0.37 pg/ml in control, р<0.05), which was normalized by enriching the diet with carnosine and α-lipoic acid. Ghrelin blood level significantly decreased in all experimental groups compared to the control: by 30% in rats fed and by almost 50% when carnosine and α-lipoic acid were added to HCCDD. The intake of α-lipoic acid led to hormone level changes in adipose tissue lysates, leptin content decreased (2.31±0.11 vs 2.77±0.15 pg/ml), while ghrelin level significantly increased (0.35±0.14 vs 0.20±0.06 pg/ml), compared with the control group (р<0.05). Conclusion. The revealed interrelation of parameters of the cellular composition of peripheral blood and hemoglobin content with the changes in the content of GM-CSF, M-CSF, leptin and ghrelin in blood plasma and adipose tissue indicates the mutual influence of the studied CSF, leptin, ghrelin and added antioxidants (carnosine and α-lipoic acid) on the regulatory mechanisms of hematopoiesis in rats fed HCCDD.

Assessment of Patients with Periorbital Melanosis for Hyperinsulinemia and Insulin Resistance.

BACKGROUND: Periorbital melanosis (PM) is one of the most common dermatological condition seen in routine practice. Several cutaneous markers such as acanthosis nigricans have been associated with insulin resistance (IR). However, the association of PM with IR needs to be substantiated. OBJECTIVE: The objective of the study is to evaluate the association of circulating adipokines and IR with PM. MATERIALS AND METHODS: In this cross-sectional study, we recruited 100 patients with PM and 100 age- and gender-matched healthy controls. The serum levels of leptin, adiponectin, fasting glucose, fasting insulin, insulin-like growth factor-1 (IGF-1), homeostatic model assessment of insulin resistance (HOMA-IR), and leptin: adiponectin ratio (L/A ratio) were assayed. RESULTS: The serum levels of leptin, fasting glucose, fasting insulin, HOMA-IR, L/A ratio were significantly higher in patients with PM as compared to controls. The serum levels of adiponectin were significantly lower in cases as compared to controls. On multivariate regression analysis, leptin, adiponectin, and HOMA-IR were found to be significant, even after adjusting for BMI, blood pressure and LDL and HDL cholesterol. CONCLUSION: Our findings suggest that patients with PM have hyperinsulinemia, IR, and elevated L/A ratio. PM as a marker of IR in adults may help in identifying patients early and thus aid in the early prevention and management of the disease.

Resting Energy Expenditure Is Not Altered in Children and Adolescents with Obesity. Effect of Age and Gender and Association with Serum Leptin Levels.

In children and adolescents, obesity does not seem to depend on a reduction of resting energy expenditure (REE). Moreover, in this young population, the interactions between either age and obesity or between age and gender, or the role of leptin on REE are not clearly understood. To compare the levels of REE in children and adolescents we studied 181 Caucasian individuals (62% girls) classified on the basis of age- and sex-specific body mass index (BMI) percentile as healthy weight (n = 50), with overweight (n = 34), or with obesity (n = 97) and in different age groups: 8-10 (n = 38), 11-13 (n = 50), and 14-17 years (n = 93). REE was measured by indirect calorimetry and body composition by air displacement plethysmography. Statistically significant differences in REE/fat-free mass (FFM) regarding obesity or gender were not observed. Absolute REE increases with age (p < 0.001), but REE/FFM decreases (p < 0.001) and there is an interaction between gender and age (p < 0.001) on absolute REE showing that the age-related increase is more marked in boys than in girls, in line with a higher FFM. Interestingly, the effect of obesity on absolute REE is not observed in the 8-10 year-old group, in which serum leptin concentrations correlate with the REE/FFM (r = 0.48; p = 0.011). In conclusion, REE/FFM is not affected by obesity or gender, while the effect of age on absolute REE is gender-dependent and leptin may influence the REE/FFM in 8-10 year-olds.

Leptin Decreases Energy Expenditure Despite Increased Thyroid Hormone in Patients With Lipodystrophy.

CONTEXT: Leptin is an adipokine that signals energy sufficiency. In rodents, leptin deficiency decreases energy expenditure (EE), which is corrected following leptin replacement. In humans, data are mixed regarding leptin-mediated effects on EE. OBJECTIVE: To determine the effects of metreleptin on EE in patients with lipodystrophy. DESIGN, SETTING, AND PATIENTS: Nonrandomized crossover study of 25 patients with lipodystrophy (National Institutes of Health, 2013-2018). INTERVENTION: The initiation cohort consisted of 17 patients without prior exposure to metreleptin, studied before and after 14 days of metreleptin. The withdrawal cohort consisted of 8 previously metreleptin-treated patients, studied before and after 14 days of metreleptin withdrawal. MAIN OUTCOMES: 24-h total energy expenditure (TEE), resting energy expenditure (REE), autonomic nervous system activity [heart rate variability (HrV)], plasma-free triiodothyronine (T3), free thyroxine (T4), epinephrine, norepinephrine, and dopamine. RESULTS: In the initiation cohort, TEE and REE decreased by 5.0% (121 ±â€…152 kcal/day; P = 0.006) and 5.9% (120 ±â€…175 kcal/day; P = 0.02). Free T3 increased by 19.4% (40 ±â€…49 pg/dL; P = 0.01). No changes in catecholamines or HrV were observed. In the withdrawal cohort, free T3 decreased by 8.0% (P = 0.04), free T4 decreased by 11.9% (P = 0.002), and norepinephrine decreased by 34.2% (P = 0.03), but no changes in EE, epinephrine, dopamine, or HrV were observed. CONCLUSIONS: Metreleptin initiation decreased EE in patients with lipodystrophy, but no changes were observed after metreleptin withdrawal. Thyroid hormone was higher on metreleptin in both initiation and withdrawal cohorts. Decreased EE after metreleptin in lipodystrophy may result from reductions in energy-requiring metabolic processes that counteract increases in EE via adipose tissue-specific neuroendocrine and adrenergic signaling.

Sex and Body Circumferences Associated with Serum Leptin in African American Adults.

Objective: Cardiovascular disease (CVD) continues to be a leading cause of death for U.S. adults, especially African Americans (AA). Yet, few studies have examined a comprehensive set of metabolic health and health behavior factors related to CVD risk in this population. This study investigated the relationship between serum leptin and anthropometries (body mass index [BMI], circumferences [waist-WC, hip-HC, and waist/hip ratio W/H]), metabolic health (systolic and diastolic blood pressure [BP], serum lipids, glucose, and C-reactive protein [CRP]), and health behaviors (hours of sleep, physical activity) in midlife and older AAs. Materials and Methods: Participants (n = 89, ≥45 years of age) were AAs in six churches in North Florida enrolled in a broader church-based longitudinal study. Anthropometric measurements, serum analyses, and self-reported items. Results: Serum leptin was positively correlated with gender (being female) (r = 0.623, p < 0.001), BMI log transformed (r = 0.469, p < 0.001), WC (r = 0.440, p < 0.001), HC (r = 0.658, p < 0.001), use of BP medication (r = 0.216, p < 0.05), and serum CRP (r = 0.277, p < 0.01). Correlations by sex showed significant relationships for both men and women between leptin and BMI log transformed, WC, and HC. The final multiple regression model [R2 = 0.758, F(4, 66) = 55.871, p < 0.001] showed that 75.8% of the variance in leptin was explained by being female (ß = 0.65, p < 0.001), WC (ß = 0.26, p < 0.02), and HC (ß = 0.28, p < 0.01). Conclusions: Findings more specifically delineate the variables associated with serum leptin in AAs, particularly WC and HC, and suggest greater attention to possible risk for leptin resistance in AA females. Clinical Trial Registration: This study is registered at www.clinicaltrials.gov NCT03339050.

Assessment of Adipokines, CXCL16 Chemokine Levels in Patients With Rheumatoid Arthritis Combined With Metabolic Syndrome.

OBJECTIVE: Rheumatoid arthritis (RA), which is a chronic systemic inflammatory disease, is associated with accelerated atherosclerosis and an increased risk of cardiovascular disease (CVD), but the causal factors have yet to be completely elucidated. The studies show that the prevalence of metabolic syndrome (MtS) was significantly higher in RA patients compared to the population. In RA and MetS inflammation and atherosclerosis are closely linked. The level of chemokines and adipokines, which may play a role in the development of atherogenesis in RA with MetS patients is currently unknown. In this study, we investigated the level of chemokine C-X-C motif chemokine ligand 16 (CXCL16) and adipokine in RA with MetS patients and assessed the association of biomarkers with clinical and biochemical activity scores of RA and components of MetS. METHODS: Blood serum of 298 people (48-patients with RA and MetS, 82-with RA without MetS, 105-with MetS, 63-control group without both RA and MetS) was tested for (CXCL16), Resistin, Leptin and Fibroblast Growth Factor 21 (FGF21) levels by fluorescent antibody technique. Statistical analysis was performed using SPSS version 18.0. RESULTS: The biomarker study showed the highest level in the RA with MetS patient group; but as compared with the RA group the differences were insignificant. CXCL16 (Me = 426.2 pg/ml (Q25-75 250.5-527.6), resistin (Me = 8685.4 pg/ml (Q25-75 6480.8-13 629.1), and FGF21 (Me = 443.6 pg/ml (Q25-75 772.9-916.3) proved to be significantly augmented in RA with MetS patients group, and in RA without MetS patients group (Me = 312.7 (Q25-75 199.4-517.7) pg/ml; Me = 8265.3 (Q25-75 5779.7-13 340.5) pg/ml; Me = 412.4 (Q25-75 300.4-497.4) pg/ml, respectively) as compared with MetS patients group (Me = 189.4 (Q25-75 130.3-280.6) pg/ml; Me = 5364.8 (Q25-75 2368.9-10 160.9) pg/ml; Me = 133.2 (Q25-75 76.2-268.6) pg/ml, respectively; P = <.001). Leptin level in all groups was higher than in the control group, but there were no differences between groups. The correlation analysis found a positive relationship between the leptin level and the waist circumference (rs = 0.39; P = .007) in the RA with MetS patients, the association of biomarkers with DAS28 score and ESR did not have any statistical significance. Conclusions: The augmented chemokine, resistin and FGF21 in the RA with MetS patients proves the systemic inflammation which is the basis of RA; the augmented leptin is linked to the abdominal obesity. These data are somewhat of an explanation of the increased risk of the CVD development in RA with MetS people. A differentiated specification can be useful to assess the cardiovascular risk of patients and justify prompt personalized treatment.

Assessment of autism-relevant behaviors in C57BKS/J leptin receptor deficient mice.

Gestational diabetes mellitus (GDM) was associated with greater autism risk in epidemiological studies. Disrupted leptin signaling may contribute to their coincidence, as it is found in both disorders. Given this we examined leptin receptor (Lepr) deficient (BKS.Cg-Dock7m +/+ Leprdb/J diabetic (db)) heterozygous (db/+) mice for autism-relevant behaviors. BKS db/+ females are lean with normal blood glucose, but they develop GDM while pregnant. We hypothesized BKS db/+ offspring might exhibit physiological and behavior traits consistent with autism. Adolescent body weight, fasting blood glucose, serum corticosterone, social preferences, self-grooming, marble burying, social dominance and cognitive flexibility of BKS db/+ mice was compared to C57BLKS/J (BKS) and C57BL/6J (BL6) mice. Male db/+ weighed more and had higher blood glucose and corticosterone relative to BL6, but not BKS mice. Also, male db/+ lacked social interaction preference, explored arenas less, and buried more marbles than BL6, but not BKS males. Male and female db/+ were more dominant and made more mistakes in water T-mazes locating a sunken platform after its position was reversed than BL6, but not BKS mice. Overall BKS db/+, particularly males, exhibited some autism-like social deficits and restrictive-repetitive behaviors relative to BL6, but BKS strain contributions to BKS db/+ behaviors were evident. Since BKS db/+ and BKS behavioral and physiological phenotypes are already so similar, it will be difficult to use these models in studies designed to detect contributions of fetal GDM exposures to offspring behaviors.