Adipokine Gene Expression Research Articles

Comparative Effects of Gymnema sylvestre and Berberine on Adipokines, Body Composition, and Metabolic Parameters in Obese Patients: A Randomized Study.

We performed a comparative study in 50 adult Mexican patients with obesity treated with GS or BBR for 3 months. The baseline and final biochemical parameters, body composition, blood pressure, gene expression of Res, Ome, Vis, and Ap, and safety parameters were evaluated. BBR significantly decreased (p < 0.05) body weight, blood pressure and Vis and Ap gene expression and increased Ome, while GS decreased fasting glucose and Res gene expression (p < 0.05). A comparative analysis of the final measurements revealed a lower gene expression of Ap and Vis (p < 0.05) in patients treated with BBR than in those treated with GS. The most frequent adverse effects in both groups were gastrointestinal symptoms, which attenuated during the first month of treatment. In patients with obesity, BBR has a better effect on body composition, blood pressure, and the gene expression of adipokines related to metabolic risk, while GS has a better effect on fasting glucose and adipokines related to insulin resistance, with minimal side effects.

Effect of Adipose Biopsy Technique on Inflammatory Markers in Adipose Tissue

Objectives: The purpose of this study was to compare adipose tissue (AT) biomarkers obtained from the Bergström and Mercedes biopsy techniques in healthy, recreationally active adults. Hypotheses: There would be no difference in expression of inflammatory and adipokine genes of interest between techniques. There would be no difference in the concentration of inflammatory cytokine levels between techniques. Methods: Basal abdominal subcutaneous AT was obtained from 12 (8M, 4F; 28±4 y; 86±8 kg; BMI 26.8±2.9 kg/m2; body fat 29±8%; VO2max 3.4±0.7 L/min) healthy, recreationally active adults (i.e., regular aerobic and/or resistance exercise 3-5 days/wk) on contralateral sides of the umbilicus via Bergström and Mercedes biopsy techniques. Inflammatory and adipokine gene expression levels (IL1β, IL6, IL8, IL10, TNFα, ADIPOQ, LEPD) were measured in AT (n=8) via qPCR. Inflammatory cytokine concentrations (GM-CSF, IFNγ, IL1β, IL2, IL5, IL6, IL8, IL12p70, IL17A, IL23, TNFα, IL4, IL10, IL13) were measured in AT (n=11) via high sensitivity discovery assay. Results: There were no differences in inflammatory nor adipokine gene expression between AT biopsy techniques (P&gt;0.05). Of the measurable cytokines (GM-CSF, IFNγ, IL8, IL17A, IL13), there were no differences between Bergström and Mercedes AT (P&gt;0.05). Average tissue yield for the Mercedes biopsy was greater than the Bergström biopsy (1007±625 mg vs. 291±83 mg, respectively; p&lt;0.05). Conclusions: The analyses performed in this study suggest AT collected from Bergström and Mercedes techniques provide high-quality RNA (RNA integrity numbers &gt;7.0) and protein with comparable basal transcriptional and translational profiles. Both techniques may be utilized in the collection of AT; however, research questions may impact the technique chosen as the Mercedes biopsy technique obtains larger tissue yields whereas the Bergström technique may allow for an increased number of biopsies due to the smaller abdominal area impacted. This research was supported by the Human Bioenergetics program at Ball State University. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Catha edulis and Cathinone Effect on Bone Parameters and Adipokines Gene Expression in Obese Male Mice

Catha edulis and Cathinone Effect on Bone Parameters and Adipokines Gene Expression in Obese Male Mice

Distinct inflammatory signatures of upper and lower body adipose tissue and adipocytes in women with normal weight or obesity.

Upper and lower body fat accumulation poses an opposing obesity-related cardiometabolic disease risk. Depot-differences in subcutaneous adipose tissue (SAT) function may underlie these associations. We aimed to investigate the inflammatory signatures of abdominal (ABD) and femoral (FEM) SAT in postmenopausal women with normal weight or obesity. We included 23 postmenopausal women with normal weight (n = 13) or obesity (n = 10). In vivo secretion of adipokines from ABD and FEM SAT was measured using the arterio-venous balance technique. Adipokine gene expression and adipocyte morphology were examined in ABD and FEM SAT. Furthermore, adipokine expression and secretion were investigated in vitro using differentiated human primary ABD and FEM subcutaneous adipocytes derived from the study participants. Plasma leptin and plasminogen activator inhibitor (PAI)-1 concentrations were higher, and ABD and FEM adipocytes were larger in women with obesity than normal weight. No differences in adipocyte size and blood flow were apparent between ABD and FEM SAT. We found significant release of leptin and monocyte chemoattractant protein (MCP)-1 from ABD and FEM SAT, with higher fractional release of MCP-1 from ABD than FEM SAT. Gene expression of leptin, PAI-1, and tumor necrosis factor-α was lower in ABD than FEM SAT and higher in women with obesity than normal weight. In ABD adipocytes, interleukin-6, PAI-1, and leptin gene expression were higher, while adiponectin and dipeptidyl-peptidase-4 gene expression were lower than in FEM adipocytes. Finally, ABD adipocytes secreted less MCP-1 compared to FEM adipocytes. These findings demonstrate that upper and lower body SAT and adipocytes are characterized by distinct inflammatory signatures in postmenopausal women, which seem independent of adipocyte size.

Expression of Locally Produced Adipokines and Their Receptors during Different Physiological and Reproductive Stages in the Bovine Corpus Luteum.

This study aimed to determine the gene expression of different local novel adipokines, such as vaspin, adiponectin, visfatin, and resistin, and their known receptors, namely, heat shock 70 protein 5, adiponectin receptor 1, and adiponectin receptor 2, in the bovine corpus luteum (CL) during different phases of the estrous cycle (on days 1-2, 3-4, 5-7, 8-12, 13-18, >18) and pregnancy (at months 1-2, 3-4, 5-7, >7). The mRNA expression was measured by reverse transcription polymerase chain reaction (RT-qPCR). The mRNA expression levels were normalized to the geometric mean of all three constantly expressed reference genes (cyclophilin A, ubiquitin, ubiquitin C). Our findings suggest that adipokines are expressed and present in all investigated groups, and are specifically up- or downregulated during the estrus cycle and during pregnancy. Vaspin and adiponectin levels were upregulated in the middle and late cycle stages. Resistin was abundant during the CL regression stage and in the first months of pregnancy. The specific expression of adipokine receptors indicates their involvement in the local mechanisms that regulate CL function. Further investigations are required to elucidate the regulative mechanisms underlying the different local effects of adipokines on the ovarian physiology of cows.

Effects of probiotics in rats with experimental metabolic syndrome and periodontitis: An investigation of the intestine-adipose tissue axis.

This study evaluated the systemic (intestine and adipose tissue) and local (periodontal tissues) impact of probiotic therapy in rats with metabolic syndrome (MS) associated or not with periodontitis (PE). Forty-eight rats received a high-fat diet for induction of MS for 16weeks. They were subdivided into groups with (+) and without (-) PE, receiving (*) or not (**) receiving probiotics (PROB): MS (-**), MSP (-*), MSPE (+**), and MSPEP (+*). PROB administration (Bifidobacterium animalis subsp. lactis HN019) started on the 8th week of the study and PE was induced on the 14th week by placing ligature on the animals' lower first molars. Euthanasia occurred in the 16th week. Biomolecular, immunoenzymatic assays, and histomorphometric analyses were performed. The data obtained were statistically analyzed (ANOVA, Tukey, p<0.05). The MSPEP group exhibited reduced alveolar bone loss when compared with the MSPE group, as well as lower levels of hepatic steatosis and proteinuria (p<0.05). In the intestinal environment, the MSPE group exhibited significantlylower villus height and crypt depth, as well as a greater increase in Bacillota when compared with the MSPEP group (p<0.05). The MSPEP group showed lower adipokine gene expression (LEPR, NAMPT, and FABP4) in adipose tissue than the MSPE group (p<0.05). The probiotic B. lactis HN019 reduced the severity of experimental periodontitis and modulated the expression of lipogenic genes and intestinal morphological and microbiological parameters in rats with MS.

Associations between subcutaneous adipocyte hypertrophy and nonalcoholic fatty liver disease

Adipocyte hypertrophy and expression of adipokines in subcutaneous adipose tissue (SAT) have been linked to steatosis, nonalcoholic steatohepatitis (NASH) and fibrosis in morbidly obese (BMI ≥ 40 kg/m2) subjects. It is unknown if this is also true for subjects with NAFLD with lesser degrees of obesity (BMI < 35 kg/m2). Thirty-two subjects with biopsy-proven NAFLD and 15 non-diabetic controls matched for BMI underwent fine-needle biopsies of SAT. Adipocyte volume was calculated. RNA-sequencing of SAT was performed in a subset of 20 NAFLD patients. Adipocyte volume and gene expression levels were correlated to the presence of NASH or significant fibrosis. Subjects with NAFLD had larger adipocyte volume compared with controls, (1939 pL, 95% CI 1130–1662 vs. 854 pL, 95% CI 781–926, p < 0.001). There was no association between adipocyte volume and the presence of NASH. Gene expression of adipokines previously described to correlate with NASH in morbid obesity, was not associated with NASH or fibrosis. Our results suggest that persons with NAFLD have larger SAT adipocytes compared with controls and that adipocytes are involved in the pathophysiology of hepatic steatosis in NAFLD. However, adipocyte volume was not associated with NASH or fibrosis in NAFLD subjects with varying degrees of obesity.

HDL AND ITS SUBPOPULATION (HDL2 AND HDL3) PROMOTE CHOLESTEROL TRANSPORTERS EXPRESSION AND ATTENUATES INFLAMMATION IN 3T3-L1 MATURE ADIPOCYTES INDUCED BY TUMOR NECROSIS FACTOR ALPHA

Obesity activates inflammation causing dysfunction of adipocytes. Increasing high-density lipoprotein (HDL) levels in obesity may be beneficial in overcoming this effect. However, not much data is available on the effects of HDL and its subpopulations in inflamed adipocytes. The objective of this study was to investigate the effects of total HDL (tHDL) and the comparison between its subpopulations (HDL2 &amp; HDL3) on protein and gene expression of cholesterol transporters, inflammation, and adipokines in TNF-α stimulated 3T3-L1 mature adipocytes. TNFα alone had lower adiponectin and higher protein and gene expression of IL-6 and NF-ĸβ (p65) compared to unstimulated adipocytes and these effects were attenuated by HDLs especially HDL3 (in most of the biomarkers). HDL and its subpopulation had higher cholesterol transporters expression in 3T3-L1 mature adipocytes induced by TNF-α compared to unstimulated cells. Increment of cholesterol transporters expression by HDL leads to reduce secretion of inflammatory markers [IL-6 &amp; NF-kB (p65)] and visfatin and increases adiponectin secretion in the inflamed mature adipocytes. HDL exhibits beyond its reverse cholesterol transporter property by exhibiting anti-inflammatory effects thru the deactivation of NF-ĸβ (p65). This may contribute to reducing the progression of obesity-related complications.

Differential effects of dolutegravir, bictegravir and raltegravir in adipokines and inflammation markers on human adipocytes

AimsTo assess the potential direct effects of the integrase strand-transfer inhibitors (INsTIs) dolutegravir, bictegravir, and raltegravir, drugs used as treatment for people living with human immunodeficiency virus (PLWH), on human adipose cells. Main methodsDrugs were added to the differentiation medium of human Simpson-Golabi-Behmel syndrome (SGBS) adipose cells and morphological adipogenesis was monitored for 10 days. Also, adipocytes were exposed to drugs following differentiation (day 14). The gene expression levels of selected adipogenesis markers, adipocyte metabolism markers, adipokines, and cytokines were determined by quantitative-reverse transcription polymerase-chain reaction. The release of adiponectin and leptin into the culture medium was measured using specific enzyme-linked immunosorbent assay, and release of interleukin-6 and chemokine (CC motif) ligand-2 using Multiplex assays. Key findingsOverall morphological adipogenesis was unaltered by INsTIs. The expression of adipogenesis marker genes (peroxisome proliferator-activated receptor-Ɣ and lipoprotein lipase) was slightly reduced in dolutegravir-treated differentiating adipocytes. Bictegravir repressed gene expression and the release of pro-inflammatory cytokines in differentiating adipocytes. Dolutegravir and raltegravir increased interleukin-6 gene expression, but only dolutegravir increased interleukin-6 release. Dolutegravir repressed adiponectin expression and release in differentiating adipocytes and had a similar but milder effect on leptin. Drug treatment of mature adipocytes reduced adiponectin gene expression in response to dolutegravir. SignificanceThe INsTIs studied do not have a significant effect on human adipose cell differentiation but exert distinct effects on gene expression and secretion of adipokines and cytokines. These findings will help understand and manage the effects of INsTI-containing treatments on body weight and metabolic dysregulation in PLWH.

Hepatic adropin is regulated by estrogen and contributes to adverse metabolic phenotypes in ovariectomized mice

ObjectiveMenopause is associated with visceral adiposity, hepatic steatosis and increased risk for cardiovascular disease. As estrogen replacement therapy is not suitable for all postmenopausal women, a need for alternative therapeutics and biomarkers has emerged. Methods9-week-old C57BL/6 J female mice were subjected to ovariectomy (OVX) or SHAM surgery (n = 10 per group), fed a standard diet and sacrificed 6- & 12 weeks post-surgery. ResultsIncreased weight gain, hepatic triglyceride content and changes in hepatic gene expression of Cyp17a1, Rgs16, Fitm1 as well as Il18, Rares2, Retn, Rbp4 in mesenteric visceral adipose tissue (VAT) were observed in OVX vs. SHAM. Liver RNA-sequencing 6-weeks post-surgery revealed changes in genes and microRNAs involved in fat metabolism in OVX vs. SHAM mice. Energy Homeostasis Associated gene (Enho) coding for the hepatokine adropin was significantly reduced in OVX mice livers and strongly inversely correlated with weight gain (r = −0.7 p < 0.001) and liver triglyceride content (r = −0.4, p = 0.04), with a similar trend for serum adropin. In vitro, Enho expression was tripled by 17β-estradiol in BNL 1 ME liver cells with increased adropin in supernatant. Analysis of open-access datasets revealed increased hepatic Enho expression in estrogen treated OVX mice and estrogen dependent ERα binding to Enho. Treatment of 5-month-old OVX mice with Adropin (i.p. 450 nmol/kg/twice daily, n = 4,5 per group) for 6-weeks reversed adverse adipokine gene expression signature in VAT, with a trended increase in lean body mass and decreased liver TG content with upregulation of Rgs16. ConclusionsOVX is sufficient to induce deranged metabolism in adult female mice. Hepatic adropin is regulated by estrogen, negatively correlated with adverse OVX-induced metabolic phenotypes, which were partially reversed with adropin treatment. Adropin should be further explored as a potential therapeutic target and biomarker for menopause-related metabolic derangement.

Gene expression of adipokines and inflammatory cytokines in peripheral blood mononuclear cells of obese dogs.

BackgroundPeripheral blood mononuclear cells (PBMCs) have been identified as a possible marker of inflammation in obesity. Understanding the expression of pro‐ and anti‐inflammatory cytokines in PBMCs in obese dogs will help control obesity‐related inflammatory diseases.ObjectivesThe aim of this study was to evaluate the role of PBMCs in obesity‐associated chronic inflammation by analyzing the expression of adipokines and inflammatory cytokines.MethodsBlood samples were obtained from 25 subjects and real‐time quantitative polymerase chain reaction determinations were performed to quantify the gene expression levels of adipokines and inflammatory cytokines, including TNF‐α, IL‐17, leptin, MCP‐1, and adiponectin, in the PBMCs.ResultsThe results showed that the gene expression levels of TNF‐α (p < 0.001), IL‐17 (p < 0.0001), and leptin (p < 0.0001) were strongly upregulated in the PBMCs of obese dogs compared to that in non‐obese dogs.ConclusionsThe changes in gene expression levels of inflammation‐related adipokines and pro‐inflammatory cytokines occur in PBMCs, which may contribute to the low‐grade chronic inflammation that is present in obesity.

Leptin and adiponectin synthesis and secretion in mature 3T3-L1 adipocytes are differentially down-regulated by arsenic and palmitic acid exposure throughout different stages of adipogenesis

AimsArsenic is a risk factor for type 2 diabetes and cardiovascular disease. However, little is known about arsenic effects over adipocyte endocrine functionality, particularly for leptin and adiponectin, and about its interaction with dietary components, which are the main environmental regulators of adipose tissue functionality. The aim of this work was to evaluate leptin and adiponectin in mature 3T3-L1 adipocytes exposed to palmitate (simulating excess fat intake), arsenite, or both throughout two different stages of adipogenesis. Material and methods3T3-L1 adipocytes were exposed starting from the beginning of its differentiation process during 11 d or once adipocytes were mature for 72 h. Adipokines secretion was evaluated by ELISA, intracellular protein levels and secreted adiponectin multimers by Western blot and mRNA abundance by qPCR. Key findingsLeptin and adiponectin secretion decreased by arsenite alone or in combination with palmitate due to reduced gene and protein expression of both adipokines. However, leptin was impaired more at the transcriptional level, whereas affections to adiponectin were more relevant at the intracellular protein amount level with changes in the multimers proportion. The gene expression of several of their transcription factors was altered. Additionally, the magnitude of the effects depends on the adipocyte cell stage at which exposure began; adiponectin was more affected when exposure started from differentiation and leptin once adipocytes were mature. SignificanceThese results in an in vivo model could be translated into less satiety and reduced insulin sensitivity.

Relationship between cardiovascular risk factors and adipocytokines gene expression in local fat depots

Abstract In this study we studied the relationships between adipokines (leptin, soluble leptin receptor) in adipose tissue (AT) and cardiovascular disease (CVD) risk factors. Methods Fat tissue biopsies were obtained from 134 patients median aged 64.0 (48.0; 68.0) with stable CAD undergoing coronary artery bypass grafting. Traditional cardiovascular risk factors and patient treatment have been recorded. AH was defined as systolic blood pressure &amp;gt;140 mm Hg Art., diastolic blood pressure &amp;gt;90 mm Hg. Dyslipidemia was defined as a previously detected increase in total serum cholesterol (&amp;gt;200 mg/dl), triglycerides (&amp;gt;200 mg/dl), or low-density lipoprotein (LDL) cholesterol (&amp;gt;150 mg/dl) for at least 1 year, or use of lipid-lowering drugs. Smoking was classified as current or former smokers; current smoking status was defined as at least one cigarette daily over the last year. Adipocytes were isolated from subcutaneous (SAT), epicardial (EAT), and perivascular AT (PVAT) samples. Isolated adipocytes were cultured for 24-h after which, Then adipocytes were immediately processed to RNA extraction and determination of adipokines gene expression. Results In this study, we showed that men with CAD LEP and LEPR expression were lower in PVAT, whereas only the latter was decreased in SAT. Thus, LEPR expression in local fat depots appeared to differ in men and women, which is consistent with previous reports. Men with CAD showed lower LEP expression than women in EAT, whereas no significant differences were observed in SAT. Patients 51–59 years old were characterized by the lowest LEP expression in SAT and the highest LEP and LEPR expression in EAT and PVAT. Those &amp;gt;60 years presented the highest levels of LEPR in SAT. The presence of dyslipidemia in patients with CAD correlated with decreased LEPR expression in EAT, which is an unfavorable sign and may potentially lead to the development of leptin resistance. In patients with AH, LEP expression in EAT and LEPR expression in SAT and PVAT is increased. AH &amp;gt;20 years was associated with increased LEP in ATs. Smokers with CAD exhibited higher levels of LEP expression in SAT and EAT, and LEPR expression in SAT. Conclusions The results of the study indicate a close association of traditional CVD risk factors with adipocytokine imbalance in patients with CAD. The results indicate the potential of the fat depot and leptin and its receptor data as a drug application point. The study of the molecular basis of PVAT and EAT function can provide a more complete understanding of the etiopathogenetic mechanisms of CVD and develop an effective strategy for their prevention and control. Funding Acknowledgement Type of funding sources: None.

The Hepatokine Adropin Is Regulated by Estrogen

Introduction: menopause is associated with weight gain, visceral adiposity and NAFLD. Rodent ovariectomy (OVX) is an accepted model for human menopause. Many OVX studies add high-fat diet or old-age to accentuate deranged phenotype. We have shown OVX alone induced weight gain and changes in liver transcriptome including downregulation of Enho, encoding for the hepatokine adropin (1). Here, we explore changes in VAT cytokine and adipokine genes, hepatic miRNA, and liver triglyceride content induced by OVX, in addition to estrogen’s role in regulation of adropin. Methods: 9-week-old C57BL/6J female mice underwent OVX or sham surgery. Groups of 10 mice were sacrificed at 6- and 12-weeks post-surgery and tissues harvested including mesenteric adipose tissue representing VAT. Liver TG was quantified using Cayman colorimetric assay. In-vitro studies performed in the murine hepatic cell-line, BNL1.ME. Adropin was measured using ELISA. Results: OVX induced adverse inflammatory cytokine & adipokine gene expression in VAT at 6-weeks post-surgery (Il18 1.1 p=0.01, Rares2 2.9, p=0.003, Retn 5.5, p=0.002) and 12-weeks post-surgery (Tnfa 2.3 p<0.001, Cxcl5 1.9 p=0.04). In the liver, OVX induced an increase in TG content at 12 weeks post-surgery (realtive increase vs sham 2.0 p=0.05). Hepatic Enho expression showed a strong inverse coorelation with total body weight gain (r= -0.7 p<0.001) and liver TG content (r=-0.4, p=0.04). In-vitro, estrogen induced an increase in Enho (relative mRNA change vs. growing medium 2.6, p=0.004); though protein level was unchanged, a trend for increased adropin was found in supernatant (relative change vs control 2.2 P=0.09). In-silico analysis of data from OVX mice treated with estrogen showed up-regulation of Enho (relative change vs vehicle, 6 p<0.001). At 6-weeks post-surgery OVX induced changes in hepatic miRNA profile with 48 miRNAs differentially expressed vs SHAM (24 up & 24 down). Integrating data from same sample RNA-SEQ and miRNA-SEQ created a network of differently expressed miRNA with oppositely differently expressed known specific mRNA targets. mIR-29, a known regulator of Enho in liver, was not found to be correlated with Enho expression in this context. Conclusions: OVX alone is sufficient to induce adverse changes in VAT gene expression and liver TG. Hepatic adropin gene expression is regulated by estrogen and its downregulation was strongly correlated to phenotypes relevant to menopause induced metabolic dysfunction, weight gain and increased liver fat. Thus, adropin should be further explored as a novel therapeutic and/or biomarker for menopause induced metabolic dysfunction. (1) Stokar, J., Gurt, I., Cohen-Kfir, E., Yakubovsky, O., Hanna, A., Assayag, E., & Dresner-Pollak, R. (2019). RNA-Seq Analysis of Ovariectomy-Induced Changes in Mouse Liver Reveals New Targets for Menopause-Associated Metabolic Derangement. Journal of the Endocrine Society, 3(Supplement_1), SUN-033.

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.

\u03c9-3PUFA supplementation ameliorates adipose tissue inflammation and insulin-stimulated glucose disposal in subjects with obesity: a potential role for apolipoprotein E

BackgroundLong chain omega-3 polyunsaturated fatty acids (ω-3PUFA) supplementation in animal models of diet-induced obesity has consistently shown to improve insulin sensitivity. The same is not always reported in human studies with insulin resistant (IR) subjects with obesity.ObjectiveWe studied whether high-dose ω-3PUFA supplementation for 3 months improves insulin sensitivity and adipose tissue (AT) inflammation in IR subjects with obesity.MethodsThirteen subjects (BMI = 39.3 ± 1.6 kg/m2) underwent 80 mU/m2·min euglycemic-hyperinsulinemic clamp with subcutaneous (Sc) AT biopsy before and after 3 months of ω-3PUFA (DHA and EPA, 4 g/daily) supplementation. Cytoadipokine plasma profiles were assessed before and after ω-3PUFA. AT-specific inflammatory gene expression was evaluated on Sc fat biopsies. Microarray analysis was performed on the fat biopsies collected during the program.ResultsPalmitic and stearic acid plasma levels were significantly reduced (P < 0.05) after ω-3PUFA. Gene expression of pro-inflammatory markers and adipokines were improved after ω-3PUFA (P < 0.05). Systemic inflammation was decreased after ω-3PUFA, as shown by cytokine assessment (P < 0.05). These changes were associated with a 25% increase in insulin-stimulated glucose disposal (4.7 ± 0.6 mg/kg ffm•min vs. 5.9 ± 0.9 mg/kg ffm•min) despite no change in body weight. Microarray analysis identified 53 probe sets significantly altered post- ω-3PUFA, with Apolipoprotein E (APOE) being one of the most upregulated genes.ConclusionHigh dose of long chain ω-3PUFA supplementation modulates significant changes in plasma fatty acid profile, AT, and systemic inflammation. These findings are associated with significant improvement of insulin-stimulated glucose disposal. Unbiased microarray analysis of Sc fat biopsy identified APOE as among the most differentially regulated gene after ω-3PUFA supplementation. We speculate that ω-3PUFA increases macrophage-derived APOE mRNA levels with anti-inflammatory properties.

A214 BARIATRIC SURGERY PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE HAVE DIFFERENT VISCERAL ADIPOSE TISSUE GENE EXPRESSION COMPARED TO THOSE WITH NORMAL LIVER

Abstract Background Non-alcoholic fatty liver disease (NAFLD) includes simple steatosis (SS) and nonalcoholic steatohepatitis (NASH). It affects 74–98% of individuals with morbid obesity undergoing bariatric surgery (BSX). Among several factors contributing to NAFLD pathogenesis, adipokines secreted by visceral adipose tissue (VAT) can play a role by regulating glucose/lipid metabolism and inflammation. Aims This study aims to determine if visceral adipose tissue adipokine and cytokine gene expression are associated with NAFLD (SS and NASH) at the time of BSX. Methods Patients were recruited from the Toronto Western Hospital Bariatric Clinic. Demographic data was recorded. The VAT and liver biopsies were collected at the time of bariatric surgery. VAT adipokines and other mediators were assessed by RT-PCR and included markers of thermogenic capacity, inflammation, fibrosis, adipokines, and others. Liver histology was assessed by a pathologist using the Brunt system and individuals were diagnosed as either SS, NASH, or having a healthy liver (HL). Blood samples were collected pre-BSX to measure liver and metabolic syndrome related parameters, including HOMA-IR, HbA1c, liver enzymes, and lipid profile. Anthropometry was also assessed. Groups were compared using Kruskal-Wallis test followed by Wilcoxon ranked sum, or chi-square and Fisher’s exact test as necessary. Data was considered to be statistically significant with a p-value less than 0.05. Results We are presenting data on 126 patients, 80.2% females with a median age of 49 and a body mass index (BMI) of 46.9. Fifty-seven patients had SS, 34 had NASH and 35 had a healthy liver (HL). BMI, age, and sex did not differ between the three groups. First, we found that those with NASH had significantly higher VAT expression of fibrosis (Loxl2), inflammation (CCL4 and TGFb1) and proliferation markers (E2F1) and significantly lower expression of adipokines (TNFa and resistin) compared to HL. Also, we found that SS had significantly higher fibrosis (Col3a1, Col6a1, Loxl2, CD9 and Acta2), inflammation (Nox2, TGFb1, IFNg and Clec10a), browning (PPARa, PPARg and Glut1) and proliferation (E2F1) marker expression compared to HL. Conclusions Results show that there is a significant difference in the expression pattern of VAT fibrotic and inflammatory markers between HL, SS and NASH patients. The observed increase of inflammatory markers in NAFLD is in line with prior research outlining the ability of inflammatory mediators from VAT to contribute to liver pathology via portal circulation. The relationship between VAT characteristics and NAFLD are important in understanding the widespread metabolic effects of obesity. Funding Agencies CIHRCanadian Liver foundation

Antioxidant and Anti-Inflammatory Potential of Polyphenols Contained in Mediterranean Diet in Obesity: Molecular Mechanisms.

Nutrition transition can be defined as shifts in food habits, and it is characterized by high-fat (chiefly saturated animal fat), hypercaloric and salty food consumption at the expense of dietary fibers, minerals and vitamins. Western dietary patterns serve as a model for studying the impact of nutrition transition on civilization diseases, such as obesity, which is commonly associated with oxidative stress and inflammation. In fact, reactive oxygen species (ROS) overproduction can be associated with nuclear factor-κB (NF-κB)-mediated inflammation in obesity. NF-κB regulates gene expression of several oxidant-responsive adipokines including tumor necrosis factor-α (TNF-α). Moreover, AMP-activated protein kinase (AMPK), which plays a pivotal role in energy homeostasis and in modulation of metabolic inflammation, can be downregulated by IκB kinase (IKK)-dependent TNF-α activation. On the other hand, adherence to a Mediterranean-style diet is highly encouraged because of its healthy dietary pattern, which includes antioxidant nutraceuticals such as polyphenols. Indeed, hydroxycinnamic derivatives, quercetin, resveratrol, oleuropein and hydroxytyrosol, which are well known for their antioxidant and anti-inflammatory activities, exert anti-obesity proprieties. In this review, we highlight the impact of the most common polyphenols from Mediterranean foods on molecular mechanisms that mediate obesity-related oxidative stress and inflammation. Hence, we discuss the effects of these polyphenols on a number of signaling pathways. We note that Mediterranean diet (MedDiet) dietary polyphenols can de-regulate nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) and NF-κB-mediated oxidative stress, and metabolic inflammation. MedDiet polyphenols are also effective in upregulating downstream effectors of several proteins, chiefly AMPK.

Effects of obesity on periodontal tissue remodeling during orthodontic movement

Orthodontic movement triggers a sequence of cellular and molecular events that may be affected by different systemic conditions. This study evaluated the effect of obesity on rat periodontal tissue remodeling induced by mechanical orthodontic force. Thirty-two Holtzman rats were distributed into 4 groups: control, obesity induction (O), orthodontic movement (M), and obesity induction and orthodontic movement (OM). Obesity was induced by a high-fat diet for 90days. After 15days of orthodontic movement, the animals were killed. Obesity induction was confirmed by animal body weight, adipose tissue weight, and serologic analysis. Periodontal tissue remodeling was evaluated using microcomputed tomography and histologic analysis. The gene expression of adipokines and cytokines in gingival tissues was evaluated. An increase in body and adipose tissue weight was observed in the obesity induction groups. The O group presented an increase in lipids and blood glucose. The OM group showed a decrease in bone volume fraction and bone mineral density compared with all other groups and a tendency for more rapid tooth movement than the M group. The OM group showed a higher quantity of inflammatory cells and higher Mmp1 expression than the O group. The O and OM groups showed higher Nampt expression than the control group and lower Nampt expression than the M group. Obesity modulates periodontal tissue remodeling during orthodontic movement and results in more inflammation and bone loss than in nonobese animals.

Androgen Reduces Mitochondrial Respiration in Mouse Brown Adipocytes: A Model for Disordered Energy Balance in Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrinopathy that is associated with an adverse metabolic profile including reduced postprandial thermogenesis. Although abnormalities in adipose tissue function have been widely reported in women with PCOS, less is known about direct effects of androgen on white and, particularly, brown adipocytes. The purpose of this study was to investigate the effect of the nonaromatizable androgen dihydrotestosterone (DHT) on (1) lipid accumulation and expression of adipogenic markers in immortalized mouse brown adipose cell lines (IMBATs), (2) mitochondrial respiration in IMBATs, (3) mitochondrial DNA content and gene expression, (4) expression of brown adipose tissue (BAT) markers and thermogenic activation. In addition, we profiled the relative levels of 38 adipokines secreted from BAT explants and looked at androgen effects on adipokine gene expression in both IMBATs and immortalized mouse white adipose (IMWATs) cell lines. Androgen treatment inhibited IMBAT differentiation in a dose-dependent manner, reduced markers of adipogenesis, and attenuated the β-adrenoceptor-stimulated increase in uncoupling protein-1 (UCP1) expression. In explants of mouse interscapular BAT, androgen reduced expression of UCP1, peroxisome proliferator-activated receptor-γ coactivator-1 (PCG-1) and Cidea. Significantly, as well as affecting genes involved in thermogenesis in BAT, androgen treatment reduced mitochondrial respiration in IMBATs, as measured by the Seahorse XF method. The results of this study suggest a role for excess androgen in inhibiting brown adipogenesis, attenuating the activation of thermogenesis and reducing mitochondrial respiration in BAT. Together, these data provide a plausible molecular mechanism that may contribute to reduced postprandial thermogenesis and the tendency to obesity in women with PCOS.