Adiponectin Protein Research Articles

Relationship between cognitive impairment and serum amyloid β-protein, adiponectin, and C-reactive protein levels in type II diabetes patients.

This study sought to explore the plausible mechanism of the cognitive impairment of patients with type 2 diabetes by analyzing the levels of serum amyloid β-protein (Aβl-42), adiponectin, and C-reactive protein (CRP). Eighty-four patients diagnosed with type 2 diabetes and 60 healthy people were selected as the participants for this study. Clinical data were collected using self-made questionnaires. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scale was used to access cognitive functions. The serum Aβl-42 and adiponectin levels were individually determined by an enzyme-linked immunoassay (ELISA). CRP was detected using a Siemens BNP II specific-protein analyzer. Patients in the case group had significantly lower immediate memory, visual span, speech function, attention, and delayed memory scores on the RBANS scale than patients in the control group. The Aβl-42 levels of patients in case group were significantly higher than those of patients in the control group. The age of patients was significantly negatively correlated to RBANS scale subtest scores and standard scores in the case group. The number of years of schooling was significantly positively correlated to immediate memory, visual span, attention, delayed memory scores, and standard scores, but negatively correlated with speech function. After adjusting for age and the number of years of schooling, the Aβl-42 levels of patients in the case group were significantly negatively correlated with immediate memory, attention, delayed memory scores, and standard scores (P<0.05). The adiponectin levels of patients in the case group were positively correlated with RBANS scale subtest scores and standard scores (P<0.05). Type 2 diabetes patients suffered from cognitive impairment. It appears that the mechanism may be associated with increased serum Aβl-42 levels, decreased adiponectin levels and inflammation reaction. The detection of serum Aβl-42 and adiponectin could be used as indicators of the degree of cognitive impairment in patients with type 2 diabetes.

Effect of a Moderate Weight Loss on Serum Fetuin-A and Markers of Inflammation in Individuals With Obesity

ObjectivesElevated fetuin-A (Fet-A) has been shown to be a risk factor for several metabolic diseases and understanding the effects of moderate weight loss on changes in Fet-A and other inflammatory markers could allow for lifestyle intervention strategies. The association of inflammatory markers and Fet-A with incremental body weight loss is unknown. The objective of the study was to evaluate the association of inflammatory markers, including TNF-alpha (TNF-α), adiponectin, and C-reactive protein (CRP), Fet-A, and it’s phosphorylated form, pFet-A, with incremental body weight loss. MethodsSixteen men achieved a targeted weight loss of 8% to 10% of initial body weight. In this study, we analyzed changes in serum TNF-α, adiponectin, and CRP inflammatory cytokines to changes in serum serum-Fet-A and pFet-A. We also examined the relationship of changes in cytokine profile to alterations in anthropometrics and other metabolic indices. All statistical analyses were performed using GraphPad Prism version 8.0. ResultsA moderate body weight loss of 8% to 10%, significantly decreased serum CRP, but did not affect TNF-α or adiponectin concentrations in individuals with obesity. Serum CRP started to decrease with 4% to 6% body weight loss, demonstrating a mean change in serum CRP concentrations of – 0.15 mg/L and – 0.10 mg/L, for 4%-6% and 8%-10% body weight loss, respectively, for each 1 kg of body weight loss. Weight-loss induced change in serum CRP concentrations were not significantly associated with a decrease in serum Fet-A or pFet-A, although a trend was observed for change in serum pFet-A (r = 0.44, P = 0.09). ConclusionsA moderate weight loss improved serum inflammatory marker C-reactive protein but did not affect TNF-α or adiponectin concentrations in individuals with obesity. These changes were not significantly associated with a decrease in serum pFet-A although a trend was observed. Funding SourcesThis work was supported by the American Diabetes Association (ADA 7–04-JF-36); the Alabama Agricultural Experiment Station (ALA080–052).

The Correlation Between Adiponectin Levels With C-Reactive Protein in Adult Obese Non-Diabetic Among Staffs of DR. M. Djamil Hospital Padang

The adiponectin and C-reactive protein (CRP) are markers of chronic low-grade inflammation related to obesity. This study aims to determine a correlation between adiponectin level and CRP level in adult obese individuals. This study was analyzed with a cross-sectional design of 55 subjects at Dr. M Jamil Central Hospital Padang from January to September 2019. The subjects included were type 1 obese (25≤BMI≤29.9 kg/m2) and type 2 obese (BMI 30.0 kg/m2). Enzyme-linked immunoassay (ELISA) was used to measure adiponectin and High Sensitivity C-Reactive Protein (Hs-CRP) levels. Univariate statistical analysis is processed and presented in distribution, frequency, mean (standard deviation), median (minimum-maximum value). Bivariate data were analyzed using the Pearson correlation test, significant if p&lt;0.05. The study consists of 16 males and 39 females. The mean age was 35 years old (the range 23 to 57 years old), the mean BMI was 30.8 (4.5) kg/m2. This study consists of 28 subjects, type 1 obese and 27 types II obese. The mean adiponectin level in type 2 obese is lower than in type 2 obese groups. The mean CRP levels are high in all populations. Pearson ln-adiponectin and CRP correlation test in the entire population: r =-0.105 (p=0.444).

The effect of the a regional cardioprotective nutritional program on inflammatory biomarkers and metabolic risk factors in secondary prevention for cardiovascular disease, a randomised trial

To evaluate the effect of the Brazilian Cardioprotective Diet Program (BALANCE Program) on inflammatory biomarkers, involved in the pathophysiology of the atherosclerosis, on inflammatory biomarkers, cardiovascular risk factors, and on plasma fatty acids in cardiovascular disease secondary prevention patients. In this substudy of the BALANCE Program randomized clinical trial, a total of 369 patients aged 45 years or older, who have experienced cardiovascular disease in the previous 10 years, were included. These patients were randomized into two groups and followed up for six months: BALANCE Program group and control group (conventional nutrition advice). In the initial and six-month final visits, anthropometry (body weight, height and waist circumference), food intake evaluation by 24-h dietary recall, plasma inflammatory biomarkers (IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-α, adiponectin, and C-reactive protein levels), blood pressure, glycemia, insulinemia, lipid profile, and plasma fatty acids levels were evaluated. The BALANCE Program group showed increased plasma alpha-linolenic acid levels (P=0.008), reduction in waist circumference (P=0.049) and BMI (P=0.032). No difference was observed among plasma inflammatory biomarkers and clinical data. After six months of follow-up, BALANCE Program led to a significant reduction on BMI and waist circumference in individuals in secondary prevention for cardiovascular disease. Although plasmatic alpha-linolenic acid has increased, there was no impact on plasma inflammatory biomarkers. NCT01620398.

Inflammatory Gene Expression in Neck Perivascular and Subcutaneous Adipose Tissue in Men With Carotid Stenosis.

The inflammatory phenotype of neck adipose tissue (NAT) might reflect its involvement in the pathogenesis of carotid atherosclerosis. We investigated inflammatory gene expression in the subcutaneous and the perivascular (pericarotid) adipose tissue from patients with carotid stenosis (CS) undergoing endarterectomy and a control group of patients without significant carotid atherosclerosis undergoing thyroid surgery. Only male patients were included (n = 13 in each study group). Clinical and biochemical data along with serum leptin, adiponectin, and monocyte chemoattractant protein 1 (MCP-1) were collected. Adipose tissue samples were obtained from both the subcutaneous and pericarotid compartments. Real-time polymerase chain reaction was used to measure gene expression of macrophage markers and adipokines. The CS group had higher subcutaneous and pericarotid visfatin gene expression and higher pericarotid expression of MCP-1 and CD68 genes. The ratio between pericarotid CD206 and CD68 gene expression was similar between study groups. Adiponectin gene expression in both NAT compartments did not differ between groups, but it was negatively associated with body weight. These observations suggest that NAT, and especially the pericarotid compartment, express enhanced inflammatory properties in patients with CS, but the proportion of anti-inflammatory macrophages in advanced atherosclerosis seems to be maintained.

Collagen β(1-O) galactosyltransferase 2 deficiency contributes to lipodystrophy and aggravates NAFLD related to HMW adiponectin in mice

AimOur previous results showed that Colgalt1 knock-out resulted in fetal death on day E11.5, and collagen secretion was retarded. This study aimed to elucidate the role of Collagen β(1-O) galactosyltransferase 2 (Colgalt2) in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). MethodsColgalt2−/− mice were fed a high-fat diet (HFD) or methionine-and choline-deficient diet (MCD). Nanopore long-read RNA-Seq analysis of liver tissues was used to profile genomic variation. In vitro, hepatocyte steatosis and differentiation of primary pre-adipocytes were induced. ResultsColgalt2−/− mice exhibited lipodystrophy, increased body weight, and hepatic lipid accumulation at 6 weeks of age. Colgalt2 deficiency aggravated hepatic steatosis in mice fed an HFD or a standard laboratory chow diet. Colgalt2 deficiency promotes steatohepatitis in MCD-fed mice. In HFD mice, Colgalt2 deficiency caused lipodystrophy and decreased plasma HMW, total adiponectin, and leptin levels. Colgalt2 deficiency also reduced circulating HMW/Total adiponectin in mice fed a HFD diet without differences of adiponectin mRNA and protein level in WT and Colgalt2−/− mice. The nanopore long-read RNA-Seq analysis results revealed transcriptional changes in the adiponectin receptor downstream signaling pathway and lipogenic genes, including the AMPK signaling pathway, adipocytokine signaling pathway, and lipid metabolism (Cidea, Cidec, CD36, and PPARγ). Colgalt2 deficiency did not promote lipid accumulation in OA-induced HepG2 cells or primary hepatocytes. However, Colgalt2 deficiency inhibited adipogenesis and reduced PPARγ, adipogenesis-related transcription factors, and expression during adipocyte differentiation. ConclusionsIn mice, Colgalt2 deficiency contributes to lipodystrophy and promotes NAFLD related to HMW adiponectin. These results suggest that Colgalt2 could be a novel and promising therapeutic strategy for the treatment of NAFLD.

Secreted frizzled-related protein 4 promotes brown adipocyte differentiation.

Secreted frizzled-related protein 4 (SFRP4) is a member of the SFRP family that contains a cysteine-rich domain homologous to the putative Wnt-binding site of frizzled proteins. In the present report, the effects of SFRP4 on murine brown adipocyte differentiation were evaluated, which exhibited an intrinsic capacity to differentiate with high efficiency. Brown preadipocytes were isolated from the scapular region of brown adipose tissue, which showed that the overexpression of recombinant active SFRP4 protein at three concentrations (1, 10 and 100 ng/ml) significantly increased the expression of adipocyte differentiation-associated genes (C/EBPα, C/EBPβ, UCP-1, PRDM16, PGC1α and GLUT4) in a dose-dependent manner compared with the control group. Secondly, adiponectin protein expression was significantly inhibited in a dose-independent manner, while leptin was increased in brown adipocytes by incubation with the high concentration (100 ng/ml) of SFRP4. Thirdly, the role of interleukin-1β (IL-1β) was investigated in brown adipocytes and discovered that IL-1β cannot induce SFRP4 mRNA expression in brown adipocytes, similar to human islet cells. These data suggested that SFRP4-treated brown adipocytes represent a valuable in vitro model for the study of adipogenesis and indicated that SFRP4 served various functions during brown adipocyte differentiation.

SIRT1 promotes lipid metabolism and mitochondrial biogenesis in adipocytes and coordinates adipogenesis by targeting key enzymatic pathways

The NAD+-dependent deacetylase SIRT1 controls key metabolic functions by deacetylating target proteins and strategies that promote SIRT1 function such as SIRT1 overexpression or NAD+ boosters alleviate metabolic complications. We previously reported that SIRT1-depletion in 3T3-L1 preadipocytes led to C-Myc activation, adipocyte hyperplasia, and dysregulated adipocyte metabolism. Here, we characterized SIRT1-depleted adipocytes by quantitative mass spectrometry-based proteomics, gene-expression and biochemical analyses, and mitochondrial studies. We found that SIRT1 promoted mitochondrial biogenesis and respiration in adipocytes and expression of molecules like leptin, adiponectin, matrix metalloproteinases, lipocalin 2, and thyroid responsive protein was SIRT1-dependent. Independent validation of the proteomics dataset uncovered SIRT1-dependence of SREBF1c and PPARα signaling in adipocytes. SIRT1 promoted nicotinamide mononucleotide acetyltransferase 2 (NMNAT2) expression during 3T3-L1 differentiation and constitutively repressed NMNAT1 and 3 levels. Supplementing preadipocytes with the NAD+ booster nicotinamide mononucleotide (NMN) during differentiation increased expression levels of leptin, SIRT1, and PGC-1α and its transcriptional targets, and reduced levels of pro-fibrotic collagens (Col6A1 and Col6A3) in a SIRT1-dependent manner. Investigating the metabolic impact of the functional interaction of SIRT1 with SREBF1c and PPARα and insights into how NAD+ metabolism modulates adipocyte function could potentially lead to new avenues in developing therapeutics for obesity complications.

The effect of adiponectin and its receptors in placental development of diabetic rats

Placenta development is an essential process for normal fetal growth and development, and healthy pregnancy maintenance. Inadequate placental development may cause clinical complications like diabetes, intrauterine growth retardation and preeclampsia. Due to limited data about placental expression of adiponectin, which has anti-diabetic effects, we studied the relationship between adiponectin and placental development in streptozotocin (STZ)-induced diabetic and normal rats. We also investigated Adiponectin receptors and the downstream adiponectin molecules like peroxisome proliferator-activated receptor (PPAR) α, PPARγ, retinoic acid receptor (RXR)α in the development of the diabetic placenta to explain the effects of Adiponectin in detail. Diabetic rat placentas were found to be heavier than control placentas at the 18th and 20th gestational days, while diabetic embryos were lighter than control group at the 14th, 18th and 20th days of gestation. Adiponectin protein level decreased in diabetic placenta towards term. Moreover, maternal serum adiponectin levels were found to be significantly decreased in diabetic group. Adiponectin receptor 1 (AdipoR1) mRNA expression levels were similar between groups, while Adiponectin receptor 2 (AdipoR2) mRNA expression was significantly decreased at the 14th, 18th and 20th days of gestation in diabetic placentas. Additionally, the mRNA and protein expression of PPARα, PPARγ, and RXRα were found to be decreased in diabetic placentas. These observations show that diabetes and pregnancy is associated with adiponectin levels. In conclusion, our data reveals that adiponectin plays a role in improvement of placental development in diabetic conditions, in the investigated animal species.

Impact of Bariatric Surgery on Body Composition and Metabolism among Obese Asian Indians with Prediabetes and Diabetes

Background: The aim of this study was to evaluate the changes in body composition, central obesity (visceral and liver fat), and pro-inflammatory markers after bariatric surgery in obese Asian Indians with prediabetes and diabetes. Materials and Methods: This is 1-year follow-up study of 30 obese patients (BMI of 30–40 kg/m2) with prediabetes and diabetes who underwent bariatric surgery at tertiary diabetes center in South India. HbA1c, adiponectin, liver enzymes, ferritin, and high-sensitivity C-reactive protein (hs-CRP) were tested before surgery and at 6 and 12 months postoperatively. Body composition analysis and ultrasound hepatic fat grading were done before and at 6 and 12 months’ post-surgery. Results: The baseline HbA1c were 8.3 ± 1.8% which reduced to 6.1 ± 0.8% at 12 months. The percent body fat, visceral fat area, and slim lean mass reduced significantly at 12 months compared with baseline (P &lt; 0.001). Hepatic steatosis and liver enzymes also significantly reduced at 12 months compared with baseline. hs-CRP and ferritin significantly reduced (P &lt; 0.05) at 12 months post-op [2.9 ± 2.8 mg/L, 39 ± 29 ng/mL] compared with baseline [7.5 ± 3.5 mg/L, 61 ± 44 ng/mL], respectively. Serum adiponectin levels significantly increased from 26.4 ± 1.4 to 67 ± 3.5 ng/mL after the surgery. Conclusion: Bariatric surgery is effective in reducing total body fat and visceral fat area, hepatic steatosis with an improvement in liver enzyme levels after bariatric surgery. hs-CRP, ferritin, and adiponectin also significantly improved following surgery.

Therapeutic potential of small extracellular vesicles derived from lipoma tissue in adipose tissue regeneration\u2014an in vitro and in vivo study

ObjectiveTo explore the adipogenic effects of the small extracellular vesicles derived from the lipoma tissues (sEV-LT), and to find a new cell-free therapeutic approach for adipose tissue regeneration.MethodsAdipose tissue-derived stem cells (ADSCs) and small extracellular vesicles derived from the adipose tissues (sEV-AT) were isolated from human adipose tissue, while sEV-LT were isolated from human lipomatous tissue. ADSCs were characterized by using flow cytometric analysis and adipogenic and osteogenic differentiation assays. sEV was identified by electron microscopy, nanoparticle tracking, and western blotting. ADSCs were treated with sEV-LT and sEV-AT, respectively. Fluorescence confocal microscopy was used to investigate whether sEV-LT and sEV-AT could be taken by ADSCs. The proliferation and migration abilities and adipogenic differentiation assay of ADSCs were evaluated by CCK-8 assays, scratch test, and oil red O staining test, and the expression levels of adipogenic-related genes C/EBP-δ, PPARγ2, and Adiponectin in ADSCs were assessed by real-time quantitative PCR (RT-PCR). The sEV-LT and sEV-AT transplantation tubes were implanted subcutaneously in SD rats, and the neotissues were qualitatively and histologically evaluated at 2, 4, 8, and 12 weeks after transplantation. Hematoxylin and eosin (H&E) staining was subsequently used to observe and compare the adipogenesis and angiogenesis in neotissues, while immunohistochemistry was used to examine the expression and the distribution of C/EBP-α, PPARγ, Adiponectin, and CD31 at the 4th week.ResultsThe in vitro experiments showed that both sEV-LT and sEV-AT could be taken up by ADSCs via endocytosis. The scratch experiment and CCK-8 experiment showed that the migration area and proliferation number of ADSCs in sEV-LT group and sEV-AT group were significantly higher than those in the non-sEV group (p < 0.05). Compared with sEV-AT group, sEV-LT group had larger migration area and proliferation number of ADSCs (p < 0.05). Oil red O staining and RT-PCR experiments showed that, compared with the non-sEVs group, the lipid droplets and the mRNA expression levels of adipogenesis-related genes PPARγ2 and Adiponectin of ADSCs in sEV-LT group and sEV-AT group were significantly upregulated (p < 0.05); however, there was no statistical significance in the expression level of C/EBP-δ (p > 0.05). In addition, no significant difference in the amount of lipid droplets and adipogenesis-related genes between the sEV-LT groups and sEV-AT was seen (p > 0.05). At 2, 4, 8, and 12 weeks, the adipocyte area and the number of capillaries in neotissues in the sEV-LT groups and sEV-AT groups were significantly increased compared with the Matrigel group (p < 0.05); however, there was no dramatic difference between sEV-LT groups and sEV-AT groups (p > 0.05). At the 4th week, neotissues in the sEV-LT groups and sEV-AT groups all showed upregulated expression of C/EBP-α, PPARγ, Adiponectin, and CD31 protein, while neotissues in the Matrigel group only showed positive expression of CD31 protein.ConclusionsThis study demonstrated that sEV-LT exerted promotion effects on adipose tissue regeneration by accelerating the proliferation, migration, and adipogenic differentiation of ADSCs in vitro and recruiting adipocytes and promoting angiogenesis in vivo. The sEV-LT could serve as an alternative cell-free therapeutic strategy for generating adipose tissue, thus providing a promising application prospect in tissue engineering.

English

BACKGROUND Obesity is a global pandemic in adolescent and adult population. Although changes in hypothalamic-pituitary-gonadal (HPG) axis with obesity is well known, there is dearth of literature from Eastern India especially with its relationship to obesity parameters, insulin resistance (IR) &amp; inflammatory markers. We wanted to study the changes in total testosterone (TT), sex hormone binding globulin (SHBG) and calculated free testosterone (cFT) with parameters of obesity [body mass index (BMI), waist, hip, neck, wrist circumference and waist-hip ratio], insulin resistance [homeostatic model assessment (HOMA) – insulin resistance (HOMA-IR) and (HOMA2-IR) and inflammation (adiponectin and high sensitivity C-reactive protein, hs-CRP)] in overweight and obese (OWOB) adolescent and adult males. METHODS An institution based cross-sectional study was done from January 2018 to January 2020 consisting of 323 male participants including adolescent and adults presenting to or being referred for overweight or obesity to the Department of Endocrinology and non-obese volunteers. RESULTS TT was lower in OWOB groups (adolescents - 216.6 ± 82.2 vs. 259.0 ± 111.1 ng / dl; P = &lt; 0.0001, adults - 392.3 ± 131.4 vs. 500.24 ± 137.8 ng / dl; P = &lt; 0.0001) compared to nonobese. Luteinizing hormone (LH), SHBG and cFT was also significantly lower in OWOB groups. Obesity parameters (except waist-hip ratio), HOMA-IR, HOMA2-IR and adiponectin correlated with TT, SHBG and cFT in OWOB adults and only TT in OWOB adolescents. Hs-CRP correlated with TT, SHBG and cFT in OWOB adults. CONCLUSIONS Testosterone was found to have a significant correlation with parameters of obesity, insulin resistance, and inflammation in overweight and obese adolescent and adult males. KEYWORDS Overweight, Obesity, Insulin Resistance, Testosterone, Hypogonadism

Adipokines and Subclinical Cardiovascular Disease in Post-Menopausal Women: Study of Women's Health Across the Nation.

BackgroundThe menopausal transition is characterized by increased cardiovascular risk, weight gain, and increased adiposity for many women. The adipose‐derived secretory proteins adiponectin and leptin are associated with insulin resistance, metabolic syndrome, and cardiovascular disease but their role in subclinical atherosclerotic disease is unclear. This cross‐sectional study evaluated the associations of adiponectin and leptin with carotid artery intima‐media thickness, adventitial diameter, presence of carotid plaques, and brachial‐ankle pulse wave velocity (baPWV) in women aged 54 to 65 years.Methods and ResultsParticipants were 1399 women from SWAN (Study of Women's Health Across the Nation), a community‐based study of women transitioning through menopause. Carotid ultrasound and baPWV measures were obtained at SWAN follow‐up visits 12 or 13, when 97% of participants were post‐menopausal. Adipokines were assayed from serum specimens obtained concurrently at these visits. Linear and logistic regression models were used to evaluate adiponectin or leptin, both log‐transformed attributable to skewness, in relationship to carotid artery intima‐media thickness, adventitial diameter, baPWV, and presence of carotid plaque. Covariates included age, race, study site, smoking, alcohol use, obesity, cardiovascular disease risk factors, and menopausal status. Lower levels of adiponectin were related to greater carotid artery intima‐media thickness, wider adventitial diameter, and faster baPWV; associations were attenuated after adjusting for cardiovascular disease risk factors. Higher levels of leptin were associated with greater carotid artery intima‐media thickness and wider adventitial diameter in minimally and fully adjusted models, and contrary to expectation, with slower baPWV, particularly among women with diabetes mellitus or obesity.ConclusionsAdiponectin and leptin are 2 important inflammatory pathways that may contribute to adverse subclinical cardiovascular disease risk profiles in women at midlife.

Adiponectin ameliorates hyperoxia-induced lung endothelial dysfunction and promotes angiogenesis in neonatal mice.

Bronchopulmonary dysplasia (BPD) is a common respiratory disease of preterm infants. Lower circulatory/intrapulmonary levels of the adipokine, adiponectin (APN), occur in premature and small-for-gestational-age infants and at saccular/alveolar stages of lung development in the newborn rat. However, the role of low intrapulmonary APN during hyperoxia exposure in developing lungs is unknown. We test the hypothesis that treatment of hyperoxia-exposed newborn mice with recombinant APN protein attenuates the BPD phenotype characterized by inflammation, impaired alveolarization, and dysregulated vascularization. We used developmentally appropriate in vitro and in vivo BPD modeling systems as well as human lung tissue. We observed reduced levels of intrapulmonary APN in experimental BPD mice and human BPD lungs. APN-deficient (APN-/-) newborn mice exposed to moderate (60% O2) hyperoxia showed a worse BPD pulmonary phenotype (inflammation, enhanced endothelial dysfunction, impaired pulmonary vasculature, and alveolar simplification) as compared to wild-type (WT) mice. Treatment of hyperoxia-exposed newborn WT mice with recombinant APN protein attenuated the BPD phenotype (diminished inflammation, decreased pulmonary vascular injury, and improved pulmonary alveolarization) and improved pulmonary function tests. Low intrapulmonary APN is associated with disruption of lung development during hyperoxia exposure, while recombinant APN protein attenuates the BPD pulmonary phenotype. Intrapulmonary APN levels were significantly decreased in lungs of experimental BPD mice and human BPD lung tissue at various stages of BPD development. Correlative data from human lung samples with decreased APN levels were associated with increased lung adhesion markers (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin). Decreased APN levels were associated with endothelial dysfunction and moderate BPD phenotype in APN-deficient, as compared to WT, experimental BPD mice. WT experimental BPD mice treated with recombinant APN protein had an improved pulmonary structural and functional phenotype. Exogenous APN may be considered as a potential therapeutic agent to prevent BPD.

Quercetin improved histological structure and upregulated adiponectin and adiponectin receptors in the placenta of rats with gestational diabetes mellitus

IntroductionGestational diabetes mellitus (GDM) is a metabolic syndrome among pregnant mothers that increases the risk of developing growth disorders in the fetus and the placenta. Adiponectin is an adipokine, which plays a central role in the regulation of glucose and lipid metabolism, energy homeostasis, and insulin resistance in various tissues. Quercetin is a natural flavonoid with beneficial effects in the diabetic animal model, but data related to its effect on histological change and adiponectin system in the placenta of GDM are limited. In the current study, some histological changes and expression of adiponectin and its two receptors in the placenta of rats with GDM were investigated. MethodsThis study was carried out on placentas from the rodent model. To induce GDM, female rats were treated with a single dose of STZ. Placenta tissue was harvested and stained by PAS method. Protein and mRNA levels of adiponectin and its two receptors were assessed by immunohistochemistry and Real time PCR analysis, respectively. ResultsThe results showed the increased number of glycogen cells and thickness of the labyrinth interhemal membrane (LIM) in the embryonic part of the placenta in diabetic rats, while the use of quercetin significantly prevented their increase in diabetic rats. Treatment of the diabetic group with quercetin caused significantly increased adiponectin expression and decreased its receptors.The immunohistochemical study revealed the expression of AdipoR2 in the cytoplasm of syncytiotrophoblast and cytotrophoblast cells. DiscussionThe results indicated that quercetin in pregnant diabetic rats could attenuate the histological abnormalities and improved adiponectin system dysregulation in the placenta.

Bariatric surgery can acutely modulate ER-stress and inflammation on subcutaneous adipose tissue in non-diabetic patients with obesity

BackgroundBariatric surgery, especially Roux-en-Y gastric bypass (RYGB), is the most effective and durable treatment option for severe obesity. The mechanisms involving adipose tissue may be important to explain the effects of surgery.MethodsWe aimed to identify the genetic signatures of adipose tissue in patients undergoing RYGB. We evaluated 13 obese, non-diabetic patients (mean age 37 years, 100% women, Body mass index (BMI) 42.2 kg/m2) one day before surgery, 3 and 6 months (M) after RYGB.ResultsAnalysis of gene expression in adipose tissue collected at surgery compared with samples collected at 3 M and 6 M Post-RYGB showed that interleukins [Interleukin 6, Tumor necrosis factor-α (TNF-α), and Monocyte chemoattractant protein-1(MCP1)] and endoplasmic reticulum stress (ERS) genes [Eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3) and Calreticulin (CALR)] decreased during the follow-up (P ≤ 0.01 for all). Otherwise, genes involved in energy homeostasis [Adiponectin and AMP-activated protein kinase (AMPK)], cellular response to oxidative stress [Sirtuin 1, Sirtuin 3, and Nuclear factor erythroid 2-related factor 2 (NRF2)], mitochondrial biogenesis [Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)] and amino acids metabolism [General control nonderepressible 2 (GCN2)] increased from baseline to all other time points evaluated (P ≤ 0.01 for all). Also, expression of Peroxisome proliferator-activated receptor gamma (PPARϒ) (adipogenesis regulation) was significantly decreased after RYGB (P < 0.05). Additionally, we observed that PGC1α, SIRT1 and AMPK strongly correlated to BMI at 3 M (P ≤ 0.01 for all), as well as ADIPOQ and SIRT1 to BMI at 6 M (P ≤ 0.01 for all).ConclusionsOur findings demonstrate that weight loss is associated with amelioration of inflammation and ERS and increased protection against oxidative stress in adipose tissue. These observations are strongly correlated with a decrease in BMI and essential genes that control cellular energy homeostasis, suggesting an adaptive process on a gene expression level during the caloric restriction and weight loss period after RYGB.Trial registration CAAE: 73,585,317.0.0000.5440

ROLE OF ADIPOSE TISSUE AND ADIPOKINES IN CHRONIC INFLAMMATION DEVELOPMENT ON METABOLIC SYNDROME BACKGROUND

The most pressing issue that combines obesity and insulin resistance is chronic subclinical inflammation, which affects the metabolic and secretory functions of adipose tissue, and is important for the development of pathological processes. The morphological basis of inflammation is the infiltration of adipose tissue by immune competent cells. Biologically active substances specific for adipose tissue are considered to be the collagen−like protein adiponectin and the protein hormone leptin, which are secreted in adipocytes. Leptin stimulates the cellular immune response and increases the production of pro−inflammatory cytokines, and adiponectin is thought to have anti−inflammatory properties. With the development of metabolic syndrome, the concentration of adiponectin in blood decreases, and that of leptin increases. To establish the relationship between serum leptin levels with markers of systemic inflammation and spontaneous production of proinflammatory cytokines as well as mononuclear blood leukocytes, an experimental study was conducted, i.e. modeling the metabolic syndrome in white female rats WAG / GSto aged 5−6 months. The predominance of proinflammatory cytokines: interleukins − 1β, −6, −8, −10, TNF−α in supernatants of mononuclear leukocytes with increasing leptin concentration, which is consistent with the view of its ability to stimulate cell immunity and affect the production of proinflammatory cytokines. It is proven that an increase in leptin levels in metabolic syndrome is not only a symptom that characterizes the functional state of adipose tissue, but also causes spontaneous production of proinflammatory cytokines and mononuclear leukocytes in blood, that is pathogenetically interrelated with the systemic inflammatory response. It is established that the change in the cytokine profile in the serum becomes a forecast of the formation and effectiveness of treatment of metabolic syndrome on the background of obesity. Key words: obesity, metabolic syndrome, undifferentiated chronic inflammation, cytokines.

Periodontal Treatment Improves Serum Levels of Leptin, Adiponectin, and C-Reactive Protein in Thai Patients with Overweight or Obesity.

Periodontitis and overweight or obesity independently change serum levels of leptin, adiponectin, and C-reactive protein (CRP). The aim of this study is to investigate the alterations of serum levels of leptin, adiponectin, and CRP after nonsurgical periodontal treatment (NSPT) in Thai patients with overweight or obesity (Owt/Ob) who did or did not exhibit severe periodontitis (SP) and normal weight (Nwt) patients with or without SP. Two hundred sixty patients were screened; 29 patients were included in this study. The study participants comprised 6 patients with Owt/Ob who exhibited SP, 11 patients with Owt/Ob who did not exhibit SP, 5 Nwt patients with SP, and 7 Nwt patients without SP. Periodontal disease status was evaluated; serum levels of leptin, adiponectin, and CRP were determined by enzyme-linked immunosorbent assay at baseline, as well as at 3 and 6 months after NSPT. At 3 months after NSPT, periodontal status was improved in all groups (p < 0.05), except Nwt patients without SP. Serum levels of leptin and CRP were significantly reduced, while serum levels of adiponectin were elevated after NSPT, regardless of bodyweight or waist circumference (p < 0.05). Improvement in serum levels of leptin after NSPT was also observed in the Nwt with SP group (p = 0.015); these levels did not significantly differ in Nwt patients without SP. NSPT reduces serum levels of leptin and CRP and enhances serum levels of adiponectin in Thai patients with Owt/Ob, irrespective of periodontitis severity. These results suggest a role for periodontal treatment in the systemic inflammatory response of Thai people with Owt/Ob.

Insulin resistance and the adiponectin/leptin ratio as a surrogate measure of insulin resistance in Japanese collegiate baseball players.

No study has previously investigated insulin resistance in collegiate baseball players. The purposes of this study were to examine: 1) the insulin resistance; and 2) the usefulness of the adiponectin/leptin (A/L) ratio compared with the homeostasis model assessment of insulin resistance (HOMA-IR) for assessing insulin resistance in collegiate baseball players. Twenty collegiate baseball players with abdominal obesity (AO group) defined by a waist circumference (WC) ≥85 cm, 65 lean baseball players with a WC<85 cm (L group), and 20 controls who were sedentary for at least 1 year (C group) were compared. The Body Mass Index, WC, systolic and diastolic blood pressures, fasting plasma glucose, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, apolipoprotein B, insulin, leptin, adiponectin, and high-sensitivity C-reactive protein (hs-CRP) were measured. The AO group had a significantly higher insulin level, HOMA-IR, and leptin level, and lower A/L ratio than the L and C groups. The AO group had a significantly higher prevalence of insulin resistance (50%) than the L (14%) group. The A/L ratio was significantly negatively correlated with body weight, Body Mass Index, WC, triglycerides, triglycerides/HDL-C ratio, apolipoprotein B, hs-CRP, insulin, HOMA-IR, and leptin, and positively correlated with HDL-C, whereas HOMA-IR was significantly positively correlated with body weight, Body Mass Index, WC, systolic and diastolic blood pressures, fasting plasma glucose, and insulin, and negatively correlated with adiponectin and the A/L ratio. In the forward stepwise multiple regression analysis, WC, triglycerides, and hs-CRP were the significant determinants for the A/L ratio, whereas diastolic blood pressure and WC were the significant determinants for HOMA-IR. This model explained 53.7% of the variance in the A/L ratio and 13.6% of the variance in HOMA-IR. The present study suggested that the baseball players with abdominal obesity had a significantly higher prevalence of insulin resistance than the lean baseball group. The A/L ratio may be more useful than HOMA-IR to accurately assess insulin resistance in male collegiate baseball players.

Incidence of Atrial Fibrillation in Postmenopausal Women with Endometrial Cancer.

Endometrial cancer (EC) has been associated with an increased risk of cardiovascular disease, including atrial fibrillation (AF). We performed a prospective, case-controlled analysis among 310 Bulgarian women with new-onset, histologically confirmed EC, free of AF at the baseline survey, and women with normal (senile) endometrium/endometrial hyperplasia as a control group (n = 205). The risk of AF as well as relationship of adiponectin (APN) and high sensitivity C-reactive protein (hs-CRP) levels with AF in women with EC were calculated by Cox proportional hazards models. During the mean follow-up of 2.5 ± 0.5 years, new-onset AF had occurred in 11.7% of women with EC vs. 5.8% in the control group (p < 0.01). The risk of AF was highest in the first 6 months after new-onset EC, with an incidence rate ratio (IRR) of 1.19 (95% CI 1.10–1.29; p = 0.01). Women with EC, who were obese (body mass index (BMI) > 30 kg/m2) and younger (age < 60) were found to be more likely to develop AF (HR 1.95; 95% CI 1.18–3.32; p = 0.05). APN levels were not significantly associated with new-onset AF (95% CI 0.87–1.21; p = 0.063). However, the secondary analysis showed evidence of APN–AF association when adjusted for BMI (2.05; 95% CI 1.04–4.04; p = 0.037). We conclude that EC was significantly associated with the incidence of AF.