Adipose Tissue Adipokines Research Articles

The impact of serum and follicular fluid secreted frizzled-related protein-5 on ICSI outcome in Iraqi infertile women with different body mass index

Introduction and Aim: Adipose tissue adipokines and cytokines impede oocyte maturation and endometrial epithelial receptivity. Secreted frizzled-related protein 5 (Sfrp5), a novel antagonist adipokine secreted by adipocytes, may have anti-inflammatory and insulin-sensitizing actions, but data is conflicting. This study examined serum and follicular fluid Sfrp5 levels in Iraqi infertile women with varying BMIs undergoing IVF/ICSI, as well as ICSI outcomes. Materials and Methods: This prospective cross-sectional study comprised 90 infertile females aged 18–45 who underwent IVF/ICSI at the High Institute of Infertility Diagnosis and Assisted Reproductive Technologies Centre in Baghdad, Iraq. Participants received antagonist ovarian hyperstimulation. All individuals' blood fasting sugar, serum fasting insulin, serum, and follicular fluid SFRP5 were tested on oocyte retrieval day. HOMA-IR was computed. Oocyte maturity and embryo morphology were categorized. Serum B-hCG was measured 14 days after embryo transfer. Results: A notable disparity was observed in the levels of serum and follicular Sfrp5, total oocyte count, mean metaphase II (MII), grade I, and pregnancy rate (p<0.05) among the participants categorized as normal weight, overweight, and obese. A notable disparity was observed in the average germinal vesicles (GV), grade III (GIII) embryos, and HOMA-IR (p < 0.05) among patients with varying body mass index (BMI) values. The study found a positive correlation between the levels of Sfrp5 in both serum and follicular fluid and the total count of oocytes, MII oocytes, grade I embryos, and pregnancy rate. However, there was a negative correlation between Sfrp5 levels and HOMA-IR, with statistical significance at p<0.05. Conclusion: Increased BMI is associated with lower serum and follicular fluid Sfrp5, reduced total oocyte count, reduced metaphase II oocyte count, more germinal vesicle oocytes, reduced embryo quality and lower pregnancy rate. Serum and follicular fluid Sfrp5 levels are negatively correlated with HOMA-IR but positively associated with ICSI outcome.

The Effect of Adiporon on Lipid Metabolism Genes Expression in Human Macrophages

Atherosclerosis is characterized by excessive uptake of cholesterol-rich low-density lipoproteins by the vascular wall macrophages. It leads to macrophage transformation into foam cells, accumulation of lipids in the intima of the arteries, atherosclerotic plaques development and following progression of cardiovascular diseases. Adiponectin, adipose tissue adipokine, has anti-atherogenic and anti-inflammatory effects that are mediated through binding to its receptors – AdipoR1 and AdipoR2. One of the mechanisms of adiponectin anti-atherogenic activity may be the participation in the regulation of reverse cholesterol transport and prevention of foam cells formation. We assumed that AdipoRon, a small-molecule adiponectin receptor agonist, could modulate the reverse cholesterol transport and inflammation genes expression in human macrophages. The aim of the present study was to investigate the effect of various concentrations of AdipoRon on the lipid metabolism ABCA1, ABCG1, APOA1, NR1H3 (LXRα), NR1H2 (LXRβ), PPARG, ACAT1 genes expression and inflammation IL6, TNFA, TLR4 genes expression in human macrophages. Primary human macrophages and THP-1 macrophages cell line were treated with various concentrations of AdipoRon. Cell viability was measured using the MTS assay. ABCA1, ABCG1, APOA1, NR1H3, NR1H2, PPARG, ACAT1, IL6, TNFA, TLR4 mRNA levels in the primary human macrophages was assessed using real-time PCR. The increase of PPARG and ABCA1 mRNA levels was shown in the primary human macrophages after 5 and 10 μM A-dipoRon treatment for 24 h. At the same time high concentration (20 μM) of AdipoRon has cytotoxic effect on macrophages, especially, on THP-1 cell line. The effect of AdipoRon on human macrophages and the investigation of potential adiponectin receptor agonists is of interest, due to the search for new approaches to the prevention and treatment of atherosclerosis.

Effect of metformin on transcriptome and adipokinome of adipocytes of local fat deposts of patients with ischemic heart disease

BACKGROUND: The information available to date on the effect of metformin on the transcriptome and secretory capacity of adipocytes in human adipose tissue (AT) is scarce and contradictory. The study analyzed whether metformin in vitro modulates gene expression and secretion of adiponectin and leptin in the AT of subcutaneous (SAT), epicardial (EAT) and perivascular (PVAT) localization of patients with ischemic artery disease (IHD).AIM: To assess the effect of metformin at various concentrations (1 and 10 mmol / L) on the level of expression of adiponectin and leptin genes and their content in adipocytes of subcutaneous, epicardial and perivascular AT of patients with IHD.MATERIALS AND METHODS: The study included 134 patients with IHD and indications for direct myocardial revascularization by coronary artery bypass grafting (CABG). During the operation, biopsies of SAT, EAT and PVAT were obtained for 3–5 gram, which served as a source of adipocytes. Isolated adipocytes were cultured for 24 hours with and without metformin (1 and 10 mmol / L). After a day of incubation, the expression of the ADIPOQ and LEP genes and the level of secretion of adiponectin and leptin in the culture medium of adipocytes were determined. Statistical processing was performed using the GraphPad Prism 6 software package (GraphPad Software, La Jolla, CA, USA) and Statistica software, 6.1 (Dell Software, Inc., Round Rock, TX, USA).RESULTS: The adipocytes of the EAT and PVAT of patients with IHD were characterized by an imbalance in the adipokine system, manifested by a low level of ADIPOQ expression and a high LEP expression in comparison with adipocytes of the SAT. Metformin increased the level of ADIPOQ expression and its secretion by adipocytes regardless of their location, while a low concentration (1 mmol / L) in adipocytes of EAT had a stronger effect compared to 10 mmol / L. Metformin had a multidirectional effect on the level of leptin in adipocytes, which depended on their localization: both in low (1 mmol / L) and high concentrations (10 mmol / L), the drug reduced the level of LEP expression and protein secretion in the culture medium of adipocytes of the SAT. EAT had no significant effect on adipocytes. In PVAT, metformin increased the expression and secretion of leptin regardless of concentration.CONCLUSION: Metformin has a direct effect on adipocytes in SAT, EAT, and PVAT and is able to modulate their activity, which is a promising strategy for maintaining the balance of adipokines in AT, especially epicardial and perivascular localization.

AdipoRon Effect on Expression of Lipid Metabolism Genes in Cultured Human Primary Macrophages

Atherosclerosis is characterized by excessive uptake of cholesterol-rich low-density lipoprotein (LDL) by vascular wall macrophages. The macrophages are transformed into foam cells, lipids accumulate in the intima of arteries, atherosclerotic plaques arise, and cardiovascular diseases develop. Adiponectin is an adipose tissue adipokine and possess anti-atherogenic and anti-inflammatory activities, which are mediated by adiponectin binding to its receptors AdipoR1 and AdipoR2. To exert its anti-atherogenic effect, adiponectin may regulate the reverse cholesterol transport and prevent foam cells formation. The small-molecule adiponectin receptor agonist AdipoRon was assumed to modulate expression of reverse cholesterol transport and inflammation genes in human macrophages. Several AdipoRon concentrations (0, 5, 10, and 20 μM) were tested for effect on expression of the lipid metabolism genes ABCA1, ABCG1, APOA1, NR1H3 (LXRα), NR1H2 (LXRβ), PPARG, and ACAT1 and the inflammation genes IL6, TNFA, and TLR4 in cultured human primary macrophages and the THP-1 macrophage cell line. Cell viability was measured using the MTS assay. ABCA1, ABCG1, APOA1, NR1H3, NR1H2, PPARG, ACAT1, IL6, TNFA, and TLR4 mRNA levels in human primary macrophages were assessed by real-time PCR. The PPARG and ABCA1 relative mRNA levels were found to increase in human primary macrophages treated with 5 or 10 μM AdipoRon for 24 h. A higher AdipoRon concentration (20 μM) was cytotoxic to macrophages, especially THP-1 cells. The effect of AdipoRon on human macrophages and potential adiponectin receptor agonists are of interest to study in view of the need to develop new approaches to atherosclerosis prevention and treatment.

Concentration of Polycyclic Aromatic Hydrocarbons (PAHs) in Human Serum and Adipose Tissues and Stimulatory Effect of Naphthalene in Adipogenesis in 3T3-L1 Cells.

Polycyclic aromatic hydrocarbons (PAHs) are one of the most prevalent classes of environmental pollutants. Some evidence shows that PAHs could be involved in human obesity. However, little is known about the distribution patterns of PAHs in human adipose tissue (AT) and the role of PAHs on adipogenesis/lipogenesis. The aims of this pilot study were to determine concentrations of 16 PAHs defined as high-priority pollutants in the plasma and adipose tissue of French and Polish bariatric patients, as well as their correlation with body mass index (BMI), plasma and AT adipokines expression levels. We finally investigated the role of naphthalene on cell proliferation, viability, and differentiation in 3T3-L1 preadipocytes. The concentration of most PAHs was similar in the three types of AT and it was significantly higher in AT as compared to plasma, suggesting bioaccumulation. Polish patients had higher PAH levels in AT than French ones. Only the concentration of naphthalene in AT was positively correlated with the BMI and serum or adipose chemerin, adiponectin and resistin expression, in French but not in Polish patients, who had significantly higher BMIs. Moreover, naphthalene exposure increased the cell proliferation of 3T3-L1 preadipocytes and lipogenesis, and increased the expression of genes involved in adipogenesis after cell differentiation. Taken together, PAHs and more particularly naphthalene could be an obesogenic molecule and increase the risk of obesity.

The acromegaly lipodystrophy.

Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) are essential to normal growth, metabolism, and body composition, but in acromegaly, excesses of these hormones strikingly alter them. In recent years, the use of modern methodologies to assess body composition in patients with acromegaly has revealed novel aspects of the acromegaly phenotype. In particular, acromegaly presents a unique pattern of body composition changes in the setting of insulin resistance that we propose herein to be considered an acromegaly-specific lipodystrophy. The lipodystrophy, initiated by a distinctive GH-driven adipose tissue dysregulation, features insulin resistance in the setting of reduced visceral adipose tissue (VAT) mass and intra-hepatic lipid (IHL) but with lipid redistribution, resulting in ectopic lipid deposition in muscle. With recovery of the lipodystrophy, adipose tissue mass, especially that of VAT and IHL, rises, but insulin resistance is lessened. Abnormalities of adipose tissue adipokines may play a role in the disordered adipose tissue metabolism and insulin resistance of the lipodystrophy. The orexigenic hormone ghrelin and peptide Agouti-related peptide may also be affected by active acromegaly as well as variably by acromegaly therapies, which may contribute to the lipodystrophy. Understanding the pathophysiology of the lipodystrophy and how acromegaly therapies differentially reverse its features may be important to optimizing the long-term outcome for patients with this disease. This perspective describes evidence in support of this acromegaly lipodystrophy model and its relevance to acromegaly pathophysiology and the treatment of patients with acromegaly.

Altered Adipose Tissue Inflammatory Markers in Mothers With Gestational Diabetes

INTRODUCTIONAdipose tissue (AT) releases adipokines and inflammatory cytokines which may have an impact on the fetus during pregnancy. Mothers with gestational diabetes (GDM) have children who have an increased risk of developing obesity and diabetes compared to children born to normal glucose tolerant (NGT) mothers, but the mechanisms are not known. AT dysfunction in mothers with GDM may play a mechanistic role in the relationship.HYPOTHESISMothers with GDM will have impaired AT mitochondrial function and increased markers of inflammation.METHODSAT tissue samples were collected from 22 NGT and 6 GDM pregnant women undergoing a C‐section. Subcutaneous (SQ) and visceral AT (VAT) samples, mother's blood, and fetal cord blood were collected. AT samples were assessed for protein expression (via Western blot) of EGF‐like module‐containing mucin‐like hormone receptor‐like 1; estrogen receptors (ERα and ERβ); adiponectin; mitochondrial oxidative phosphorylation (Ox‐phos) C1‐5; nuclear factor kappa‐light‐chain‐enhancer of activated B cells; adipose triglyceride lipase (ATGL) and a panel of inflammatory, mitochondrial, and metabolic genes via quantitative real time polymerase chain reaction. Mother’s blood and cord blood were assessed for presence of adiponectin, brain derived neurotrophic factor, C‐reactive protein. and non‐esterified fatty acids via enzyme‐linked immunoassay.RESULTSIn GDM compared to NGT mothers, VAT had significantly lower protein expression levels of Ox‐phos C2 and adiponectin (p=0.009 and 0.008 respectively) and trended towards significance for ATGL and Ox‐phos C3 (p=0.05 and 0.06 respectively). Gene expression of adiponectin and ERβ also tended to be lower in GDM mothers (p=0.05 and 0.06 respectively). In SQAT, higher gene expression of mannose receptor C‐type 1 (anti‐inflammatory macrophage marker) in the GDM mothers was found (p=0.037). No differences in the measured blood markers were found.CONCLUSIONData support that mothers with GDM differentially express AT adipokines and genes associated with inflammation, insulin resistance and altered lipid metabolism than mothers with NGT.

Near-roadway air pollution, immune cells and adipokines among obese young adults

BackgroundAir pollution has been associated with metabolic disease and obesity. Adipokines are potential mediators of these effects, but studies of air pollution-adipokine relationships are inconclusive. Macrophage and T cells in adipose tissue (AT) and blood modulate inflammation; however, the role of immune cells in air pollution-induced dysregulation of adipokines has not been studied. We examined the association between air pollution exposure and circulating and AT adipokine concentrations, and whether these relationships were modified by macrophage and T cell numbers in the blood and AT.MethodsFasting blood and abdominal subcutaneous AT biopsies were collected from 30 overweight/obese 18–26 year-old volunteers. Flow cytometry was used to quantify T effector (Teff, inflammatory) and regulatory (Treg, anti-inflammatory) lymphocytes and M1 [inflammatory] and M2 [anti-inflammatory]) macrophage cell number. Serum and AT leptin and adiponectin were measured using enzyme-linked immunosorbent assay (ELISA). Exposure to near-roadway air pollution (NRAP) from freeway and non-freeway vehicular sources and to regional particulate matter, nitrogen dioxide and ozone were estimated for the year prior to biopsy, based on participants’ residential addresses. Linear regression models were used to examine the association between air pollution exposures and adipokines and to evaluate effect modification by immune cell counts.ResultsAn interquartile increase in non-freeway NRAP exposure during 1 year prior to biopsy was associated with higher leptin levels in both serum [31.7% (95% CI: 10.4, 52.9%)] and AT [19.4% (2.2, 36.6%)]. Non-freeway NRAP exposure effect estimates were greater among participants with greater than median Teff/Treg ratio and M1/M2 ratio in blood, and with greater M1 counts in AT. No adipokine associations with regional air pollutants were found.DiscussionOur results suggest that NRAP may increase serum leptin levels in obese young adults, and this association may be promoted in a pro-inflammatory immune cell environment in blood and AT.

Saponin-rich extract of Tribulus terrestris alleviates systemic inflammation and insulin resistance in dietary obese female rats: Impact on adipokine/hormonal disturbances

Tribulus terrestris saponins (TTS) have been longley used as an overall tonic and recent studies showed they influence inflammatory conditions. We examined the ameliorative effect of a commercial formula of a saponin-rich extract of TT in a model of dietary obesity in female rats focusing on their ability to control the inflammatory burden, insulin resistance (IR), adipokine expression and the related reproductive system pathologies. Female rats were fed with high fat diet (HFD) for 14 weeks to launch diet-induced obesity; they were assigned as: the obese control female rats (OFR) which received no treatment and TTS (5 and 10 mg/kg/day) treated rats; they were compared to a normal rat group. We determined the IR index, serum/tissue inflammatory cytokines, and adipose tissue adipokine expression and examined the secondary ovarian pathologies. Body weight gain, serum triglycerides and IR (>5-fold) in the OFR group were greater than the normal group; TTS lessened these parameters compared with the OFR group. TTS, at 10 mg/kg dose, ameliorated mRNA expression of leptin and visfatin genes in addition to serum inflammatory cytokine levels. Moreover, TTS corrected the hyperprolactinemia and other hormonal disturbances and ameliorated the ovarian pathologies. This study highlighted that the anti-inflammatory properties of TTS helped in alleviation of IR and body weight gain in OFR. Upon correction of obesity manifestations, the gonadal hormone dysregulations and ovarian pathologies were subsequently ameliorated. We can consider TTS as a promising candidate that may alleviate the inflammatory burden, IR and adipokine expression in obesity and hence prevent the secondary gonadal complications in female subjects if appropriate clinical studies are available.

Omentin-1 gene expression is gender specific influenced by PPARγ

Background and Aims: Introduction: Adipose tissue adipokine omentin-1 is considered as potential biomarker of obesity-related cardiovascular diseases and diabetes. Peroxisome proliferator activated receptor PPARγ provides transcriptional control of adipogenesis and adipokine secretion. Aim of the study was to investigate omentin-1 and PPARG genes expression in adipose tissue from patients with obesity, metabolic syndrome (MS) and coronary artery disease (CAD).

Melanoma Progression under Obesity: Focus on Adipokines.

Simple SummaryObesity is a rapidly growing public health problem and the reason for numerous diseases in the human body, including cancer. This article reviews the current knowledge of the effect of molecules secreted by adipose tissue-adipokines on melanoma progression. We also discuss the role of these factors as markers of incidence, metastasis, and melanoma patient survival. Understanding the functions of adipokines will lead to knowledge of whether and how obesity promotes melanoma growth.Obesity is a growing problem in the world and is one of the risk factors of various cancers. Among these cancers is melanoma, which accounts for the majority of skin tumor deaths. Current studies are looking for a correlation between obesity and melanoma. They suspect that a potential cause of its development is connected to the biology of adipokines, active molecules secreted by adipose tissue. Under physiological conditions, adipokines control many processes, including lipid and glucose homeostasis, insulin sensitivity, angiogenesis, and inflammations. However, when there is an increased amount of fat in the body, their secretion is dysregulated. This article reviews the current knowledge of the effect of adipokines on melanoma growth. This work focuses on the molecular pathways by which adipose tissue secreted molecules modify the angiogenesis, migration, invasion, proliferation, and death of melanoma cells. We also discuss the role of these factors as markers of incidence, metastasis, and melanoma patient survival. Understanding the functions of adipokines will lead to knowledge of whether and how obesity promotes melanoma growth. Further studies may contribute to the innovations of therapies and the use of adipokines as predictive and/or prognostic biomarkers.

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

FABP4 and omentin-1 gene expression in epicardial adipose tissue from coronary artery disease patients.

Omentin-1 and fatty acid-binding protein 4 (FABP4) are adipose tissue adipokines linked to obesity-associated cardiovascular complications. The aim of this study was to investigate epicardial adipose tissue (EAT) omentin-1 and FABP4 gene expression in obese and non-obese patients with coronary artery disease (CAD). Omentin-1 and FABP4 mRNA levels in EAT and paired subcutaneous adipose tissue (SAT) as well as adipokine serum concentrations were assessed in 77 individuals (61 with CAD; 16 without CAD (NCAD)). EAT FABP4 mRNA level was decreased in obese CAD patients when compared to obese NCAD individuals (p=0.001). SAT FABP4 mRNA level was decreased in CAD patients compared to NCAD individuals without respect to their obesity status (p=0.001). Omentin-1 mRNA level in EAT and SAT did not differ between the CAD and NCAD groups. These findings suggest that omentin-1 gene expression in adipose tissue is not changed during CAD; downregulated FABP4 gene expression in SAT is associated with CAD while EAT FABP4 gene expression is decreased only in obesity-related CAD.

Адипокины жировой ткани в патогенезе ожирения и ишемической болезни сердца

Дисбаланс в секреции адипокинов жировой тканью при ожирении может играть роль в развитии сердечно-сосудистых заболеваний. Нами было проведено исследование уровня экспрессии генов адипонектина и оментина-1 в жировой ткани у лиц с ожирением и ишемической болезнью сердца (ИБС). Показано, что сниженные концентрация в сыворотке крови и экспрессия гена адипонектина в подкожной жировой ткани могут вносить вклад в развитие ИБС при ожирении. ИБС ассоциирована с низкой концентрация оментина-1 в сыворотке крови. Imbalance in the secretion of adipose tissue adipokines may play a role in the development of cardiovascular diseases associated with obesity. Investigation of adiponectin and omentin-1 genes expression levels in adipose tissue was conducted in patients with obesity and coronary artery disease (CAD). Our study has shown that reduced adiponectin serum concentration and subcutaneous adipose tissue gene expression may contribute to CAD development. CAD is associated with a low serum omentin-1 concentration.

The NLRP3 inflammasome regulates adipose tissue metabolism.

Adipose tissue regulates metabolic homeostasis by participating in endocrine and immune responses in addition to storing and releasing lipids from adipocytes. Obesity skews adipose tissue adipokine responses and degrades the coordination of adipocyte lipogenesis and lipolysis. These defects in adipose tissue metabolism can promote ectopic lipid deposition and inflammation in insulin-sensitive tissues such as skeletal muscle and liver. Sustained caloric excess can expand white adipose tissue to a point of maladaptation exacerbating both local and systemic inflammation. Multiple sources, instigators and propagators of adipose tissue inflammation occur during obesity. Cross-talk between professional immune cells (i.e. macrophages) and metabolic cells (i.e. adipocytes) promote adipose tissue inflammation during metabolic stress (i.e. metaflammation). Metabolic stress and endogenous danger signals can engage pathogen recognition receptors (PRRs) of the innate immune system thereby activating pro-inflammatory and stress pathways in adipose tissue. The Nod-like receptor protein 3 (NLRP3) inflammasome can act as a metabolic danger sensor to a wide range of pathogen- and damage-associated molecular patterns (PAMPs and DAMPs). Activation of the NLRP3 inflammasome facilitates caspase-1 dependent production of the pro-inflammatory cytokines IL-1β and IL-18. Activation of the NLRP3 inflammasome can promote inflammation and pyroptotic cell death, but caspase-1 is also involved in adipogenesis. This review discusses the role of the NLRP3 inflammasome in adipose tissue immunometabolism responses relevant to metabolic disease. Understanding the potential sources of NLRP3 activation and consequences of NLRP3 effectors may reveal therapeutic opportunities to break or fine-tune the connection between metabolism and inflammation in adipose tissue during obesity.

Role of Complement and Complement-Related Adipokines in Regulation of Energy Metabolism and Fat Storage.

Adipose tissue releases many cytokines and inflammatory factors described as adipokines. In obesity, adipokines released from expanding adipose tissue are implicated in disease progression and metabolic dysfunction. However, mechanisms controlling the progression of adiposity and metabolic complications are not fully understood. It has been suggested that expanding fat mass and sustained release of inflammatory adipokines in adipose tissue lead to hypoxia, oxidative stress, apoptosis, and cellular damage. These changes trigger an immune response involving infiltration of adipose tissue with immune cells, complement activation and generation of factors involved in opsonization and clearance of damaged cells. Abundant evidence now indicates that adipose tissue is an active secretory source of complement and complement-related adipokines that, in addition to their inflammatory role, contribute to the regulation of metabolic function. This article highlights advances in knowledge regarding the role of these adipokines in energy regulation of adipose tissue through modulating lipogenic and lipolytic pathways. Several adipokines will be discussed including adipsin, Factor H, properdin, C3a, Acylation-Stimulating Protein, C1q/TNF-related proteins, and response gene to complement-32 (RGC-32). Interactions between these factors will be described considering their immune-metabolic roles in the adipose tissue microenvironment and their potential contribution to progression of adiposity and metabolic dysfunction. The differential expression and the role of complement factors in gender-related fat partitioning will also be addressed. Identifying lipogenic adipokines and their specific autocrine/paracrine roles may provide means for adipose-tissue-targeted therapeutic interventions that may disrupt the vicious circle of adiposity and disease progression. © 2019 American Physiological Society. Compr Physiol 9:1411-1429, 2019.

Effects of resveratrol and its analogue pterostilbene, on NOV/CCN3 adipokine in adipose tissue from rats fed a high-fat high-sucrose diet.

Nephroblastoma overexpressed protein, also called NOV/CCN3, is an adipokine which is present in various tissues and recently linked to obesity. The objective of the study was to determine the effect of resveratrol and pterostilbene on NOV/CCN3 in adipose tissue from rats fed an obesogenic diet. Thirty-six male Wistar rats were split into four groups (n = 9): fed a standard diet (CC), high-fat high-sucrose (HFS) diet supplemented with resveratrol (RSV; 30mg/kg/day) or with pterostilbene (PT; 30mg/kg/day), or without phenolic supplementation (HFS). Rats were sacrificed after 6weeks of treatment, and adipose tissue (white and brown) from different anatomical locations were dissected. Then, Nov/ccn3 gene and protein expression and the adipogenic genes, Ucp-1 and Pgc-1a, expressions were studied. Increased weight of white adipose tissues was found in rats fed the HFS diet. Whereas resveratrol-treated rats showed reduced internal and total adipose tissue weights, pterostilbene-treated rats showed reduced subcutaneous, internal and total adipose depots. Nov/ccn3 gene expression decreased in epididymal and interscapular brown depot in rats fed HFS diet when compared with the control group. Regarding the phenolic compounds, resveratrol prompted a Nov/ccn3 gene expression increase in epididymal fat tissue, whereas pterostilbene reduced its protein expression compared with the obese group. However, these phenolic compounds did not affect NOV/CCN3 expression in brown depot. NOV/CCN3 seems to be involved in weight changes in epididymal adipose tissue under obesogenic feeding, but not in subcutaneous, acting as a protective mechanism counteracting the fattening effect of the diet. To our knowledge, this is the first study analyzing whether NOV/CCN3 is involved in the anti-obesity effect of resveratrol and pterostilbene. Our results suggest that this is not the case.

Increased Adipocyte Size, Macrophage Infiltration, and Adverse Local Adipokine Profile in Perirenal Fat in Cushing's Syndrome.

To analyze changes in fat cell size, macrophage infiltration, and local adipose tissue adipokine profiles in different fat depots in patients with active Cushing's syndrome. Subcutaneous (SC) and perirenal (PR) adipose tissue of 10 patients with Cushing's syndrome was compared to adipose tissue of 10 gender-, age-, and BMI-matched controls with regard to adipocyte size determined by digital image analysis on hematoxylin and eosin stainings, macrophage infiltration determined by digital image analysis on CD68 stainings, and adipose tissue leptin and adiponectin levels using fluorescent bead immunoassays and ELISA techniques. Compared to the controls, mean adipocyte size was larger in PR adipose tissue in patients. The percentage of macrophage infiltration of the PR adipose tissue and PR adipose tissue lysate leptin levels were higher and adiponectin levels were lower in SC and PR adipose tissue lysates in patients. The adiponectin levels were also lower in the SC adipose tissue supernatants of patients. Associations were found between the severity of hypercortisolism and PR adipocyte size. Cushing's syndrome is associated with hypertrophy of PR adipocytes and a higher percentage of macrophage infiltration in PR adipose tissue. These changes are associated with an adverse local adipokine profile.

Cardiotrophin‐1 Regulates Adipokine Production in 3T3‐L1 Adipocytes and Adipose Tissue From Obese Mice

Cardiotrophin-1 (CT-1) belongs to the IL-6 family of cytokines. Previous studies of our group revealed that CT-1 is a key regulator of glucose and lipid metabolism. The aim of the present study was to analyze the in vitro and in vivo effects of CT-1 on the production of several adipokines involved in body weight regulation, nutrient metabolism, and inflammation. For this purpose, 3T3-L1 adipocytes were incubated with recombinant protein CT-1 (rCT-1) (1-40 ng/ml) for 1 and 18 h. Moreover, the acute effects of rCT-1 administration (0.2 mg/kg, i.v.) for 30 min and 3 h on adipokines levels were also evaluated in high-fat fed obese mice. In 3T3-L1 adipocytes, rCT-1 treatment downregulated the expression and secretion of leptin, resistin, and visfatin. However, rCT-1 significantly stimulated apelin mRNA and secretion. rCT-1 (18 h) also promoted the activation by phosphorylation of AKT, ERK 1/2, and STAT3. Interestingly, pre-treatment with the PI3K inhibitor LY294002 reversed the stimulatory effects of rCT-1 on apelin expression, suggesting that this pathway could be mediating the effects of rCT-1 on apelin production. In contrast, acute administration of rCT-1 (30 min and 3 h) to diet-induced obese mice downregulated leptin and resistin, without significantly modifying apelin or visfatin mRNA in adipose tissue. Furthermore, CT-1 null mice exhibited altered expression of adipokines in adipose tissue. The present study demonstrates that rCT-1 modulates the production of adipokines in vitro and in vivo, suggesting that the regulation of the secretory function of adipocytes could be involved in the metabolic actions of this cytokine. J. Cell. Physiol. 232: 2469-2477, 2017. © 2016 Wiley Periodicals, Inc.

Experimental type 2 diabetes induction reduces serum vaspin, but not serum omentin, in Wistar rats.

Vaspin and omentin are adipose tissue adipokines that have often been related to obesity and its comorbidities. The aim of this study was to investigate the behaviour of serum omentin and vaspin in models of type 2 diabetes. To do this, Wistar rats (~200g) were randomly divided into two groups: a non-diabetic group (n=6) and a diabetic group fed on a high-fat diet (n=6) and a low dose of streptozotocin (Sigma® ). All procedures were approved by the Brazilian Ethics Committee. Body weight (BW) and food intake were recorded daily. Tail blood glucose levels were assessed at the end of the diabetes induction period. The insulin tolerance test (ITT) was performed after the diabetes induction period (7weeks). The serum and tissues (liver, pancreas, and retroperitoneal (RET), epididymal (EPI) and visceral (VIS) white adipose tissues) were immediately removed and weighed. Analyses of levels of insulin, omentin, vaspin, adiponectin and inflammatory cytokines IL-6, IL-8 (CXCL8), TNF-α and C-reactive protein (CRP) in serum were performed using the enzyme-linked immunosorbent assay (ELISA). Our results showed that IL-8 and CRP serum levels in the diabetic group were significantly higher than in the non-diabetic group. Vaspin and adiponectin values were lower for the diabetic group than for the non-diabetic group. Omentin, IL-6 and TNF-α values did not differ between the groups. Our results showed that both the metabolism of the adipose tissue and the secretion of adipokines may be affected in diabetic rats. Omentin showed no difference between the groups, although the vaspin values decreased in the diabetic group.