Higher Leptin Levels Research Articles

Hyperandrogenism, Insulin Resistance, and Acanthosis Nigricans (HAIR-AN) Syndrome Reflects Adipose Tissue Dysfunction (“Adiposopathy” or “Sick Fat”) in Asian Indian Girls

Background: Whether HAIR-AN syndrome and polycystic ovarian syndrome (PCOS) are distinct entities or represent a phenotypic spectrum of the same syndrome is still unclear. HAIR-AN syndrome is characterized by high insulin resistance, obesity, and hyperinsulinemia as compared to PCOS and could represent adipose tissue dysfunction as the primary pathophysiologic trigger. This study was undertaken to study the role of adipose tissue dysfunction in HAIR-AN syndrome and PCOS using adipocytokines as surrogate markers of “adiposopathy.” Materials and Methods: A cross-sectional observational study was conducted at a tertiary care hospital over a period of 1 year. Serum adiponectin, leptin, IL-6, and TNF-α levels were measured in 30 women with HAIR-AN syndrome and in 30 women with PCOS. Correlations between adipocytokines, inflammatory markers, serum testosterone, and serum insulin were determined. Data analysis was performed using the SPSS version 23.0 (IBM SPSS Statistics Inc., Chicago, IL, USA) software program. Results: Women with HAIR-AN syndrome had significantly higher hyperandrogenemia, hyperinsulinemia, and insulin resistance as compared to PCOS women. They also had high leptin levels and lower adiponectin levels (p < 0.001). However, the levels of inflammatory markers (TNF-α and IL-6) were similar in both the groups (p > 0.05). Serum adiponectin showed a negative correlation with HOMA-IR and testosterone levels, while leptin showed a positive correlation with both in HAIR-AN patients while no such correlation was found in the PCOS group. Conclusion: The significantly raised adipocytokines in HAIR-AN syndrome patients as compared to PCOS patients indicates the primary role of adipose tissue dysfunction (“adiposopathy”) in the pathogenesis of HAIR-AN syndrome while only a minor role, if any, in PCOS. Both these syndromes stand as distinct entities pathogenically with an overlapping phenotype.

Adiponectin, Leptin and Cardiovascular Disorders.

The landmark discoveries of leptin and adiponectin firmly established adipose tissue as a sophisticated and highly active endocrine organ, opening a new era of investigating adipose-mediated tissue crosstalk. Both obesity-associated hyperleptinemia and hypoadiponectinemia are important biomarkers to predict cardiovascular outcomes, suggesting a crucial role for adiponectin and leptin in obesity-associated cardiovascular disorders. Normal physiological levels of adiponectin and leptin are indeed essential to maintain proper cardiovascular function. Insufficient adiponectin and leptin signaling results in cardiovascular dysfunction. However, a paradox of high levels of both leptin and adiponectin is emerging in the pathogenesis of cardiovascular disorders. Here, we (1) summarize the recent progress in the field of adiponectin and leptin and its association with cardiovascular disorders, (2) further discuss the underlying mechanisms for this new paradox of leptin and adiponectin action, and (3) explore the possible application of partial leptin reduction, in addition to increasing the adiponectin/leptin ratio as a means to prevent or reverse cardiovascular disorders.

Leptin correlates with monocytes activation and severe condition in COVID-19 patients.

Excessive monocyte activation with the development of excessive or uncontrolled release of proinflammatory cytokines often results in host tissue injury and even death in patients with pneumonia caused by the 2019 novel coronavirus. However, the changes of cytokine profiles of coronavirus disease 2019 (COVID-19) patients, as well as the underlying mechanisms that are involved, remain unknown. Using a cytokine array containing 174 inflammation-related cytokines, we found significantly altered cytokine profiles in severe COVID-19 patients compared with those in mild patients or healthy controls, and identified leptin, CXCL-10, IL-6, IL-10, IL-12, and TNF-α as the top differentially expressed cytokines. Notably, leptin showed high consistency with CXCL-10 and TNF-α in predicting disease severity, and correlated with body mass index, decreased lymphocyte counts, and disease progression. Further analysis demonstrated that monocytes in severe patients with higher leptin levels were inclined toward M1 polarization. Mechanistic studies revealed that leptin synergistically up-regulated expression levels of inflammatory cytokines and surface markers with IL-6 in monocytes through STAT3 and NF-κB signaling pathways. Collectively, our results suggest that overweight COVID-19 patients were prone to have higher leptin levels, which further activated monocytes, resulting in amplified or dysregulated immune responses. Taken together, our findings argue that leptin correlates severity of COVID-19 and may indicate a possible mechanism by which overweight patients have a greater tendency to develop severe conditions.

Sex Differences in Macrophage Responses to Obesity-Mediated Changes Determine Migratory and Inflammatory Traits.

The mechanisms whereby obesity differentially affects males and females are unclear. Because macrophages are functionally the most important cells in obesity-induced inflammation, we sought to determine reasons for male-specific propensity in macrophage migration. We previously determined that male mice fed a high-fat diet exhibit macrophage infiltration into the hypothalamus, whereas females were protected irrespective of ovarian estrogen, in this study, we show that males accumulate more macrophages in adipose tissues that are also more inflammatory. Using bone marrow cells or macrophages differentiated in vitro from male and female mice fed control or high-fat diet, we demonstrated that macrophages derived from male mice are intrinsically more migratory. We determined that males have higher levels of leptin in serum and adipose tissue. Serum CCL2 levels, however, are the same in males and females, although they are increased in obese mice compared with lean mice of both sexes. Leptin receptor and free fatty acid (FFA) receptor, GPR120, are upregulated only in macrophages derived from male mice when cultured in the presence of FFA to mimic hyperlipidemia of obesity. Unless previously stimulated with LPS, CCL2 did not cause migration of macrophages. Leptin, however, elicited migration of macrophages from both sexes. Macrophages from male mice maintained migratory capacity when cultured with FFA, whereas female macrophages failed to migrate. Therefore, both hyperlipidemia and hyperleptinemia contribute to male macrophage-specific migration because increased FFA induce leptin receptors, whereas higher leptin causes migration. Our results may explain sex differences in obesity-mediated disorders caused by macrophage infiltration.

Adipokines and the risk of active TB: a nested case-control study.

BACKGROUND: Adipokines are emerging mediators of immune response, and may affect susceptibility to active TB.OBJECTIVE: To examine the associations between adipokines and the risk of active TB.METHODS: In a case-control study nested within a prospective cohort of middle-aged and older adults in Singapore, 280 incident active TB cases who donated blood for research before diagnosis were matched with 280 controls. Serum levels of adiponectin, resistin, leptin and ghrelin were measured. Multivariable logistic regression models were used to compute the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between adipokines and the risk of active TB.RESULTS: Higher levels of leptin and resistin were associated with reduced risk of TB in a dose-dependent manner. Compared to those in the lowest quartile of leptin levels, those in the highest quartile had an OR of 0.46 (95%CI 0.26-0.82; P for trend = 0.009). Similarly, compared to those in the lowest quartile of resistin levels, those in the highest quartile had an OR of 0.46 (95%CI 0.24-0.90; P for trend = 0.03). Adiponectin and ghrelin levels were not associated with TB risk.CONCLUSION: Increased serum levels of leptin and resistin may be associated with reduced susceptibility to active TB infection.

PECULIARITIES OF HEMODYNAMIC AND METABOLIC INDICATORS IN PATIENTS WITH ARTERIAL HYPERTENSION AND CONCOMITANT OBESITY DEPENDING ON PLASMA RENIN ACTIVITY

The aim of the research: to evaluate the effect of plasma renin activity on the state of hemodynamic and neurohumoral parameters in obese hypertensive patients. Anthropometric, biochemical, automated methods of immune analysis, spectrophotometric, instrumental, statistical methods were used to examine 200 hypertensive patients with class I–II obesity aged 45–55 years. Patients were divided into two groups depending on plasma renin activity: the first group included 21 patients with low-renin hypertension, the second – 179 patients with high-renin hypertension. Patients with HRAH had higher blood pressure BP (DBP, p = 0.004, SBP and mean blood pressure, p&lt;0.001 for both indicators), higher CIMT bifurcation (p = 0.003) and cPWV (p = 0.023), larger size of the left ventricle and its MM (p = 0.039) compared with patients with LRAH. The HRAH was associated with a more pronounced imbalance of the oxidative stress system – antioxidant protection, higher levels of leptin, total cholesterol and LDL cholesterol. In the absence of differences in glycemic levels, patients with HRAH had significantly higher insulin levels and more pronounced IR, as assessed by the HOMA index. Patients with low plasma renin activity had significantly lower serum aldosterone levels with significantly higher ARR levels than patients with high plasma renin activity. Features of cardiovascular remodeling and neurohumoral status depending on the phenotype of hypertension in patients with concomitant obesity have been established.

Serum 25OHD3 of Obese Mice Is Affected by Liver Injury and Correlates with Testosterone Levels and Sperm Motility

Introduction: The concentration of 25-hydroxycholecalciferol (25OHD₃) in the serum of obese people is low and often accompanied by symptoms of low fertility. Therefore, vitamin D is recommended as a potential treatment option. However, after clinical trials, it was found that vitamin D cannot effectively increase the concentration of 25OHD₃ in the serum of obese people. How obesity causes low 25OHD₃ concentration and low fertility is unclear. Methods: We analyzed the physiological and pathological changes in obese mice induced by a high-fat diet (HFD) and the changes in mice after supplementing with 25OHD₃. Results: The concentration of 25OHD₃ in the serum of obese mice induced by HFD was significantly reduced, and these mice showed liver hypertrophy accompanied by abnormal liver injury, testicular hypertrophy, low testosterone levels, high leptin levels, and low sperm motility. The mRNA and protein expression of CYP2R1 of hydroxylated vitamin D₃ was significantly reduced; CYP11A1 and CYP11A2, which synthesize testosterone, were significantly reduced. After supplementing with 25OHD₃, there was an increase in serum 25OHD₃ concentration, testosterone level, and sperm motility, but it cannot improve the degree of obesity, CYP2R1 expression, and liver damage. Conclusion: Our research shows that there is a metabolic interference mediated by 25OHD₃ and testosterone between obesity and low sperm motility. The results of this study can provide a scientific basis for studying the mechanism of 25OHD₃ and hormone regulation and treating obese people with low sperm motility.

Relationship between Serum Leptin Values and Abdominal Circumference Assessed in the First Trimester of Pregnancy in Obese Women.

Higher serum leptin values have been correlated with several complications of pregnancy, while the abdominal circumference (AC) is an anthropometric measurement usually used to diagnose abdominal obesity. For this study we compared serum leptin levels between two groups of pregnant women: those with abdominal obesity (AC>88cm) and those without abdominal obesity (AC<88cm), diagnosed at the beginning of pregnancy. Serum leptin levels were obtained through measurements performed between 11-14 and 28-32 weeks of gestation. Higher serum leptin levels were found in the group of pregnant women with abdominal obesity comparing to the group without abdominal obesity, but a positive correlation between abdominal circumference and the leptin values was found only at 11-14 weeks of pregnancy. Our study showed that a simple measurement of AC performed at the beginning of pregnancy may predict the average serum levels of leptin throughout the gestation period. A better understanding of the role of leptin during development is needed to make us able to know how maternal-placental-fetal leptin exchange influence the fetal development.

Evaluation of Leptin and HOMA-Adiponectin in Hypothyroid Infertile Females

Introduction:Thyroid hormones and leptin is a perfect pair that maintains homeostasis of metabolic profile and abnormality in thyroid hormone levels potentiates insulin resistant state.The intriguing relationship between obesity and hypothyroidism is related by the key element leptin leading to consequent clinical implications. The severity of insulin resistance in hypothyroid and adipocytokine levels relate to the chance of pregnancy in infertile women. Aim:To assess the Leptin, insulin resistance and HOMA-adiponectin in Hypothyroid infertile women. Settings and Design:It is an Observational Cross-sectional work conducted in women with 20 to 40 years of age. About 180 infertile females were screened at the Obstetric&amp; Gynecology OPD. 86 married women were categorized as groups: Euthyroid (A) –included fertile women who had TSH and FT4 within normal reference range. Subclinical Hypothyroidism (B) - infertile women with raised TSH ranging from 4.6 – 20 mIU/ml and normal FT4 Overt hypothyroid (C)- includedinfertile women with elevated TSH greater than 20 mIU/ml and decreased free T4 level. Methods and Material:Measurement of adiposity indices that includes calculated parameters such as BMI, WHR, waist circumference / height ratio and body roundness index. Fasting serum sample was collected and analysed for FT3, FT4, TSH, prolactin, insulin. Using Biovendor and DRG Human kit based on ELISA; Adiponectin and Leptin levels was estimated respectively. HOMA-IR and HOMA-adiponectin were calculated. Results:Mean Leptin concentrations and HOMA-adiponectin were significantly increased (p &lt; 0.01) in Overt hypothyroid infertile women as compared to euthyroid and subclinical hypothyroid infertile women. Leptin had significantly positive correlation with TSH, FT3/FT4 ratio whereas negatively correlated with FT4. Significant positive correlation was observed with HOMA-IR and HOMA- adiponectin in hypothyroid infertile women. Conclusions:The study concludes that in hypothyroid infertile women having high leptin levels with reduced insulin sensitivity as related with increased HOMA-adiponectin. Analysis of thyroid profile, insulin sensitivity state along with leptin is mandatory to regulate ovulatory process in infertile women.

Metabolic syndrome as a factor influencing the course of pregnancy

Background. According to the WHO guidelines, the criteria for metabolic syndrome (MS) include obesity (body mass index (BMI) &gt;30 kg/m2), abdominal obesity (ratio of waist circumference and hips circumference &gt;0.85 for females), blood pressure &gt;160/90 mm Hg, triglyceride level &gt;1.7 mmol/l, impaired glucose tolerance, microalbuminuria &gt;20 μg/min.&#x0D; Objective. To assess the impact of MS on pregnancy.&#x0D; Materials and methods. Analysis of literature data on this issue and our own study involving 38 obese women. Pregnant women in the study were tested for pregnancy-associated protein A (PAPP-A), placental growth factor (PIGF), arginine, and leptin. They were also prescribed a comprehensive preventive treatment (from 12 weeks of pregnancy – 150 mg of aspirin 1 g per day, from 16 weeks – L-arginine solution (Tivortin aspartate, “Yuria-Pharm”) 5 ml (1 g) 4 times per day for 2 months). The control group consisted of 30 healthy pregnant women, the comparison group – of 30 obese pregnant women who did not receive L-arginine.&#x0D; Results and discussion. The pathological consequences of the mother’s MS for the foetus are mediated by the insulin resistance, hyperglycemia, and vascular damage. The negative effects include birth injuries, caesarean section, childhood obesity, and cardiovascular disease. Eclampsia and preeclampsia (PE), which increase the risk of perinatal mortality, are also the important problems of modern obstetrics. The presence of obesity in pregnant women increases the likelihood of PE by 2-3 times. Pre-pregnancy BMI increase by 5-7 kg/m2 also doubles the risk. In addition to PE, obesity also increases the risk of gestational hypertension, premature birth, foetal growth retardation syndrome, macrosomia, gestational diabetes mellitus, sudden foetal death. Endothelial dysfunction (ED) is one of the main pathogenetic links of obstetric complications, primarily PE. Thus, hypertension in PE is a consequence of impaired endothelial control of vascular tone, proteinuria and oedema – of increased vascular permeability, coagulopathy – of overexpression of procoagulants. In obesity, the likelihood of PE increases as chronic inflammation and ED are induced. PE development is also mediated by the increase in the leptin concentration. Nitric oxide donors, namely L-arginine, should be prescribed to correct ED and prevent PE. According to the results of our own study, obese women in the first trimester had significantly higher leptin levels and significantly lower PIGF levels, which is a prerequisite for PE and other gestational complications. In the main group, compared to the comparison group, there was a lower frequency of early moderate PE (5 % vs. 8 %), early severe PE (1 % vs. 5 %), moderate PE after 34 weeks of pregnancy (8 % vs. 12 %), and severe PE after 34 weeks of pregnancy (1 % vs. 4 %).&#x0D; Conclusions. 1. Obesity significantly increases the risk of PE and other gestational complications. 2. The main mechanisms of adverse effects of obesity are chronic inflammation and ED. 3. The use of complex prophylaxis with aspirin and L-arginine for 2 months almost 5 times reduced the degree of severe early PE.

Endotypes identified by cluster analysis in asthmatics and non-asthmatics and their clinical characteristics at follow-up: the case-control EGEA study

BackgroundIdentifying relevant asthma endotypes may be the first step towards improving asthma management. We aimed identifying respiratory endotypes in adults using a cluster analysis and to compare their clinical characteristics...

Adipokines and Arterial Stiffness in the Elderly.

IntroductionThe aim of this study was to evaluate the relationship between adipokines and arterial stiffness in a group of 85 elderly subjects and the role of leptin and adiponectin on subclinical vascular damage, defined by a PWV>10 m/s.MethodsIn each subject, we evaluated anthropometry, body composition by DXA (fat mass, fat mass%, lean mass), metabolic variables, leptin, adiponectin, systolic, diastolic, mean arterial pressure and pulse pressure (SBP, DBP, MAP, PP), carotid-femoral pulse wave velocity (cfPWV) and carotid-radial pulse wave velocity (crPWV).ResultsIn the study population, significant associations were observed between cfPWV and crPWV, age, SBP, MAP, waist circumference, fat body mass and leptin. The study population was subdivided in 2 subgroups according to adipokine patterns: group 1 included patients with high adiponectin and low leptin, and group 2 patients had high leptin and low adiponectin. SBP, PP, cfPWV were significantly higher in subjects with high leptin and low adiponectin (group 2). Even after adjustment for gender, fat mass%, MAP, HDL cholesterol and triglycerides, cfPWV was higher in group 2 than group 1. In a logistic binary regression on the entire population, considering subclinical vascular damage as a dependent variable and age, gender, MAP, fat mass%, triglycerides, HDL cholesterol and category of subjects with high leptin and low adiponectin as independent variables, MAP and category of subjects with high leptin and low adiponectin were significant predictors (OR, respectively, 1.09 and 3.61).ConclusionIn conclusion, in the elderly, the presence at the same time of high leptin levels and low adiponectin levels seems to have synergic effects on arterial stiffness.

The association of leptin and adiponectin with hepatocellular carcinoma risk and prognosis: a combination of traditional, survival, and dose-response meta-analysis

BackgroundAn increasing number of studies have focused on the association between leptin, adiponectin levels and the risk as well as the prognosis of hepatocellular carcinoma. However, the reported results are conflicting.MethodsA meta-analysis was performed to assess the correlation between leptin, adiponectin levels and risk and prognosis of hepatocellular carcinoma (CRD42020195882). Through June 14, 2020, PubMed, Cochrane Library and EMBASE databases were searched, including references of qualifying articles. Titles, abstracts, and main texts were reviewed by at least 2 independent readers. Stata 16.0 was used to calculate statistical data.ResultsThirty studies were included in this meta-analysis and results showed that hepatocellular carcinoma group had significantly higher leptin levels than the cancer-free control group (SMD = 1.83, 95% CI (1.09, 2.58), P = 0.000), the healthy control group (SMD = 4.32, 95% CI (2.41, 6.24), P = 0.000) and the cirrhosis group (SMD = 1.85, 95% CI (0.70, 3.01), P = 0.002). Hepatocellular carcinoma group had significantly higher adiponectin levels than the healthy control group (SMD = 1.57, 95% CI (0.37, 2.76), P = 0.010), but no statistical difference compared with the cancer-free control group (SMD = 0.24, 95% CI (− 0.35, 0.82), P = 0.430) and the cirrhosis group (SMD = − 0.51, 95% CI (− 1.30, 0.29), P = 0.213). The leptin rs7799039 polymorphism was associated with increased risk of hepatocellular carcinoma (G vs A: OR = 1.28, 95% CI (1.10, 1.48), P = 0.002). There were linear relationships between adiponectin levels and the risk of hepatocellular carcinoma (OR = 1.066, 95% CI (1.03, 1.11), P = 0.001). In addition, the results showed that high/positive expression of adiponectin was significantly related to lower overall survival in hepatocellular carcinoma patients (HR = 1.70, 95% CI (1.22, 2.37), P = 0.002); however, there was no significantly association between the leptin levels and overall survival (HR = 0.92, 95% CI (0.53, 1.59), P = 0.766).ConclusionThe study shows that high leptin levels were associated with a higher risk of hepatocellular carcinoma. Adiponectin levels were proportional to hepatocellular carcinoma risk, and were related to the poor prognosis.

Hyperleptinemia as a contributing factor for the impairment of glucose intolerance in obesity.

Obesity has emerged as a major risk factor for insulin resistance leading to the development of type 2 diabetes (T2D). The condition is characterized by high circulating levels of the adipose-derived hormone leptin and a state of chronic low-grade inflammation. Pro-inflammatory signaling in the hypothalamus is associated with a decrease of central leptin- and insulin action leading to impaired systemic glucose tolerance. Intriguingly, leptin not only regulates body weight and glucose homeostasis but also acts as a pro-inflammatory cytokine. Here we demonstrate that increasing leptin levels (62,5µg/kg/d, PEGylated leptin) in mice fed a high-fat diet (HFD) exacerbated body weight gain and aggravated hypothalamic micro- as well as astrogliosis. In contrast, administration of a predetermined dose of a long-acting leptin antagonist (100 µg/kg/d, PESLAN) chosen to block excessive leptin signaling during diet-induced obesity (DIO) showed the opposite effect and significantly improved glucose tolerance as well as decreased the total number of microglia and astrocytes in the hypothalamus of mice fed HFD. These results suggest that high levels of leptin, such as in obesity, worsen HFD-induced micro-and astrogliosis, whereas the partial reduction of hyperleptinemia in DIO mice may have beneficial metabolic effects and improves hypothalamic gliosis.

Abstract 13525: The Association Between Multiparity and Adipokine Levels: The Multi-Ethnic Study of Atherosclerosis (MESA)

Background: Multiparity is a risk factor for cardiovascular disease (CVD). However, the mechanism of this relationship is unknown. Adipokines may predispose multiparous women to certain cardiometabolic complications that can increase their risk of future CVD. Methods: We studied 975 female MESA participants (ages 45-84 yrs and initially free of CVD) who had complete data on parity assessed at baseline and adipokine levels measured at either Exam 2 or 3. Parity was categorized as nulliparity (reference), 1-2, 3-4 and ≥5 live births. Multivariable linear regression was used to evaluate the association of parity categories with log-transformed levels of leptin, resistin, and adiponectin. Results: The women (38% white, 23% black, 13% Chinese, and 26% Hispanic) had mean age at MESA visit 2/3 of 63±9 yrs. Median adipokine levels by parity group are shown in the Table . Compared to nulliparity, a history of 3-4 live births was associated with higher leptin levels, even after full covariate adjustment including body mass index (BMI) and CVD risk factors (model 4). Grand multiparity (≥5 births) was associated with greater leptin after adjustment for demographic and lifestyle factors (models 1 &amp; 2), but these associations were no longer significant after BMI adjustment (model 3). Grand multiparity was also associated with lower adiponectin levels in demographic/lifestyle-adjusted models but not after adjustment for BMI. In contrast, grand multiparity remained associated with higher resistin levels after full covariate adjustment (model 4). Conclusions: In a multiethnic U.S. cohort of women, multiparity is associated with adipokine levels, specifically with higher leptin and resistin levels. Further studies are needed to determine whether adipokines mediate the relationship between multiparity and CVD.

High levels of leptin and non-high molecular weight-adiponectin in patients with colorectal cancer: Association with chemotherapy and common genetic polymorphisms.

Colorectal cancer (CRC) is the third most frequently diagnosed cancer worldwide. Leptin and adiponectin are hormones produced by adipose tissues, which exhibit opposing effects on tumor growth. Leptin promotes tumor development and metastasis, whereas adiponectin attenuates this. The aim of the present study was to assess the possible association between leptin and adiponectin [both high molecular weight (HMW) and non-HMW factions] levels with CRC, CRC response to chemotherapy, and to study the relationship between LEPR (rs6588147), ADIPO (rs266729), LEP (rs2167270), and ADIPO (rs822369) polymorphisms and CRC. A total of 32 blood samples collected from CRC patients were analyzed to identify the serum levels of leptin and adiponectin, and the presence of CRC related polymorphisms. A total of 25 healthy subjects were recruited in the control group. Serum levels of leptin and adiponectin were detected using ELISA whereas DNA from patients and controls was amplified and analyzed using PCR-restriction fragment length polymorphism assay. The results showed that the levels of leptin and non-HMW adiponectin were significantly higher in CRC patients compared with the controls (P<0.05). In addition, HMW adiponectin was significantly higher in patients receiving chemotherapy. The association between LEPR (rs6588147), ADIPO (rs266729), LEP (rs2167270) and ADIPO (rs822369) polymorphisms and CRC was not significant (P>0.05). In conclusion, higher leptin and non-HMW adiponectin levels may be associated with increased CRC. Chemotherapy may positively influence the levels of HMW adiponectin. No association between LEPR (rs6588147), ADIPO (rs266729), LEP (rs2167270) and ADIPO (rs822369) polymorphisms with CRC was found.

Association between plasma leptin/adiponectin ratios with the extent and severity of coronary artery disease

BackgroundLeptin can have a direct effect on endothelial and vascular smooth muscle cells and high level of leptin is involved in the pathogenesis of atherosclerosis. This study aimed to determine the relationship between leptin/adiponectin (L/A) ratio and the extent and severity of coronary artery disease (CAD).MethodsThis case-control study was conducted in an educational hospital in Ilam, Iran from June 2014 to September 2015. Totally 300 participants including 150 patients with CAD (case group) and 150 healthy individuals (control group) were selected and their plasma leptin, adiponectin and leptin/adiponectin ratio was measured. The extent and severity of coronary artery disease were assayed based on the number of involved vessels and Gensini score (GS) and the relation between scores and L/A findings were compared between cases and controls.ResultsTotally, 300 participants including 150 (42.7% male), mean age 59.5 ± 11.4 years as cases and 150 (50.7% male), mean age 59.8 ± 10.7 as controls were analyzed. Plasma level of leptin and L/A ratio were higher in cases compared to controls, but level of adiponectin was significantly lower in CAD patients than the control group. More number of involved coronary vessels was significantly correlated to higher level of plasma leptin, L/A ratio and lower level of adiponectin among case group. Moreover, adiponectin was negatively and leptin or L/A ratio were positively correlated with number of involved vessels. 7.3% of cases had only one involved vessel, 42.7% had two involved vessels, and 50% of total patients had involved vessels and the mean ± SD of GS in the case group was 23.6 ± 6.9.ConclusionsPlasma levels of leptin, and adiponectin can indicate the extent of coronary artery diseases but leptin may be a better marker of extent of CAD than either L/A ratio or adiponectin separately.

The aging mouse microbiome has obesogenic characteristics

BackgroundDuring aging, there is a physiological decline, an increase of morbidity and mortality, and a natural change in the gut microbiome. In this study, we investigated the influence of the gut microbiome on different metabolic parameters in adult and aged mice.MethodsFecal and blood samples from adult (n = 42, 100–300 days) and aging (n = 32, 550–750 days) mice were collected. Microbiome analysis was done using QIIME2. Mouse weight and body composition were measured using NMR, and insulin and leptin levels in the blood were measured with Mouse Adipokine Magnetic Bead Panel kit. Fecal microbiota transplantation experiments from adult and aged mice into young germ-free mice were carried out in order to examine the effect of the gut microbiome of adult and aging mice on weight, body composition, insulin, and leptin.ResultsWe demonstrate that the microbiomes from adult and aged mice are distinguishable. We also report changes in metabolic parameters as we observed significantly higher weight and fat mass and low lean mass in aged compared to adult mice along with high insulin and leptin levels in the blood. The transplanted gut microbiome from aged mice transferred part of the phenotypes seen in aged mice. Fat body mass and insulin levels were higher in the mice who received feces from aged mice than mice receiving feces from adult mice. In addition, they consumed more food and had a higher respiratory quotient compared to mice receiving adult feces.ConclusionsWe conclude that aged mice have a gut microbiota with obesogenic characteristics. In addition, the gut bacterial population itself is sufficient to induce some of the manifestations of obesity.

Susceptibility of the obese population to COVID-19

•Obesity is a risk factor for disease severity in individuals with coronavirus disease (COVID-19). However, the increased susceptibility of this population to COVID-19 is unclear. We outline several underlying mechanisms that may explain the relationship between obesity and COVID-19 severity. Obesity has an adverse effect on respiratory physiology because increased intra-abdominal adipose tissue can interfere with lung expansion, resulting in reduced lung compliance. Further, fat accumulation in the soft tissue of the pharynx can increase inspiratory resistance, and obesity may be associated with sleep apnea. Obesity is associated with several defects in cell-mediated immunity, including increased levels of pro-inflammatory cytokines. Impaired adipocyte-mediated immune function results in chronically high leptin levels, low adiponectin levels, and anti-inflammatory adipokines. Reduced physical activity can impair several steps of the immune response to viruses. Obesity also promotes a hypercoagulable state, leading to severe consequences. These factors may synergistically play a role in promoting the severity of the disease in obese individuals. A better understanding of the mechanisms by which obesity contributes to the severity of COVID-19 is important for developing more effective treatments.

ASSOCIATION OF ADIPOKINES AND OBESITY-RELATED PATHWAYS WITH LUNG FUNCTION AND PULMONARY VASCULAR DISTENSIBILITY

SESSION TITLE: Pulmonary Manifestations of Systemic Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Obesity has multifactorial effects on lung function and pulmonary hypertension. The contributions of adipose related cytokine (adipokine) pathways to alterations in lung function remain unclear. In this context, we examined the role of adipokines and obesity-related biomarkers in relationship to pulmonary function and dynamic pulmonary vascular response to exercise. METHODS: We examined patients who underwent clinically indicated cardiopulmonary exercise testing (CPET) with invasive hemodynamic monitoring at Massachusetts General Hospital between December 2006 and June 2017. We excluded patients with low LVEF or who failed to reach adequate exercise threshold (defined at RER>1.0). We examined the association of adiponectin, leptin, resistin, IL6, CRP, and insulin resistance (HOMA-IR) with pulmonary function (% predicted FEV1, FVC, FEV1/FVC, TLC and DLCO) using multivariable linear regression. Analyses were adjusted for age, sex, BMI, smoking status, diabetes, prior MI, and heart failure. Adipokines were log-transformed and standardized. RESULTS: Among 695 individuals (mean age 57 years, 60% women), we found that leptin, CRP and HOMA-IR were all associated with lower FEV1, FVC, TLC and DLCO (multivariable p<0.05 for all), with minimal effect on FEV1/FVC ratio indicating restrictive physiology. For example, a 1-SD higher leptin level was associated with a 3% lower FEV1, 2.7% lower FVC, 4.5% lower TLC and 3.5% lower DLCO (p<0.05 for all). By contrast, adiponectin was associated with lower FEV1 and FEV1/FVC ratio (p<0.05 for both), indicating obstructive physiology. In addition, leptin, resistin, IL6, CRP, and HOMA-IR were associated with lower peak VO2 (p<=0.001 for all). When examining measures of pulmonary vascular function, we observed that higher adiponectin, IL6, and CRP were associated with worse pulmonary distensibility, and higher leptin, IL6, and CRP were associated with worse pulmonary artery compliance (p<0.05 for all). CONCLUSIONS: Adipokines and obesity-related pathways including leptin, IL6, CRP, and HOMA-IR were associated with worse pulmonary function in a pattern suggestive of restrictive physiology, in addition to worse functional capacity. IL6 and CRP were associated with both a lower pulmonary artery distensibility and compliance. CLINICAL IMPLICATIONS: Adipokine and obesity-related biomarkers were associated with restrictive lung physiology demonstrated by a reduction in % predicted FEV1, FVC, TLC and DLCO. In addition, higher levels of adipokines, in particular IL6 and CRP, demonstrated worsening pulmonary distensibility as well as pulmonary compliance indicating a negative effect on the pulmonary vascular system. These results may shed light onto potential mechanisms by which obesity can lead to lung disease and pulmonary hypertension. DISCLOSURES: No relevant relationships by Robyn Farrell, source=Web Response No relevant relationships by Jennifer Ho, source=Web Response No relevant relationships by Emily Lau, source=Web Response no disclosure on file for Gregory Lewis; No relevant relationships by Elizabeth Liu, source=Web Response Owner/Founder relationship with Patch Please note: >$100000 Added 04/06/2020 by Rajeev Malhotra, source=Web Response, value=Ownership interest Consultant relationship with Third Pole Please note: $1001 - $5000 Added 04/06/2020 by Rajeev Malhotra, source=Web Response, value=Consulting fee Consultant relationship with MyoKardia Please note: $20001 - $100000 Added 04/06/2020 by Rajeev Malhotra, source=Web Response, value=Consulting fee No relevant relationships by Jenna McNeill, source=Web Response No relevant relationships by Matthew Nayor, source=Web Response No relevant relationships by John Sbarbaro, source=Web Response No relevant relationships by Mark Schoenike, source=Web Response No relevant relationships by Emily Zern, source=Web Response