Adipose Tissue-derived Cytokines Research Articles

Association Between CYP2C19 Genotypes With Clinical Phenotypes and Adipokine Levels Among Ischemic Stroke Patients: A Prospective Observational Study.

Background Cytochrome P450 system is implicated in vascular pathologies, including stroke. Besides its role as a drug metabolizer, it also plays an important role in the metabolism of several endogenous substances like fatty acids, arachidonic acid, etc., which have pro-inflammatory effects. On the other hand, leptin and adiponectin are two of the most common adipose tissue-derived cytokines (adipokines), which are pro-inflammatory andanti-inflammatory in nature,respectively. Both of them are implicated in the pathogenesis of stroke. Methods We prospectively recruited ischemic stroke patients (within three months of occurrence of an attack of stroke). The occurrence of composite outcome (recurrence of transient ischemic attack/ischemic stroke or death)was evaluated for association with genetic variants of CYP2C19 (allele *2, *17, *3, and *4, i.e., single nucleotide polymorphism (SNP) 1/2/3/4, identified using TaqMan assays and DNA sequencing). Adiponectin and leptin levels weredetermined usingan enzyme-linked immunosorbent assay. Comparisons were made betweenstroke vs. control patients and between CYP2C19 intermediate metabolizer (IM)/poor metabolizer (PM) vs. extensive metabolizer (EM)/ultra metabolizer (UM) (PM: *2/*2; IM: *1/*2vs. EM: *1/*1; UM: *1/*17). P < 0.05 was taken as the threshold for statistical significance. Results A total of 204 patients and 101 controls were recruited. With regardto the occurrence of stroke, SNP2 showed a significant positive association. Haplotypes (SNP1/SNP2) AC (OR = 1.75 (1.08-2.83), p= 0.024) and GT (OR = 3.33 (1.53-7.22), p = 0.0026) were strongly associated with the occurrence of ischemic stroke even after adjustment for age and sex (global haplotype association p-value: 0.0062). Haplotype phenotype gender interaction was evident. Among stroke patients, with regardto composite outcome, only SNP1 showed a positive association. The AC haplotype was significantly associated with the occurrence of composite outcome (OR = 2.27 (1.17-4.41), p = 0.016). Among stroke patients, a significant positive association was seen between death and SNP1 (OR = 2.35 (1.13-4.90), p = 0.021) and AC haplotype (OR = 2.73 (1.20-6.22), p = 0.018). However, none of the SNPs or haplotypes showed any association with recurrence. Significant higher leptin and lower adiponectin levels were observed among stroke patients compared to controls.Leptin levels were higher in IM/PM group. IM/PM phenotypes showed a higher incidence of occurrence of composite outcome (hazard ratio = 2.07 (0.96-4.47), p = 0.056). Conclusion CYP2C19 polymorphisms may play a significant role in the pathogenesis of stroke. Leptin could serve as a prominent biomarker of atherosclerosis and inflammation in the early post-stroke period; however, further study is warranted with a larger sample size.

Advances in "adiponcosis": Insights in the inner mechanisms at the base of adipose and tumour tissues interplay.

The epidemic spread of obesity is nowadays recognized as a global health and economic burden, arising great interest in the scientific community. The rate of adult obesity steadily increases concomitantly with the cancer incidence. As has been comprehensively reported, obesity is included among the multiple cancer risk factors and can progressively cause and/or exacerbate certain cancer types, as colorectal and breast cancers. The term adiponcosis was forged precisely to emphasize the interconnection between obesity and cancer onset and progression. The underlying mechanisms of adiponcosis have not been fully elucidated yet, may vary on cancer type, and depend on body fat distribution. It has been proposed that insulin resistance and related chronic hyperinsulinemia, increased insulin-like growth factors production, chronic inflammation or increased bioavailability of steroid hormones could be responsible of cancer hallmarks. Additionally, it has been suggested that adipose tissue-derived hormones, cytokines and adipokines, such as leptin, adiponectin and inflammatory markers, may reflect mechanisms linked to tumorigenesis. This review summarizes the current evidence on pathways, hormones, cytokines and low-chronic inflammation subtending adiponconsis, focusing on breast and colorectal cancers. In addition, we analyzed the lifestyle interventions that could attenuate the driving forces of obesity-related cancer incidence and progression. Moreover, current targets and drugs, their pros and cons, as well as new mechanisms and targets with promising therapeutic potential in cancer are discussed. Depicting this complex interconnection will provide insights for establishing new therapeutic approaches to halt the obesity impacts and thwart cancer onset and progression.

Role of adipose tissue-derived cytokines in the progression of inflammatory breast cancer in patients with obesity

BackgroundInflammatory breast cancer (IBC) represents a deadly aggressive phenotype of breast cancer (BC) with a unique clinicopathological presentation and low survival rate. In fact, obesity represents an important risk factor for BC. Although several studies have identified different cellular-derived and molecular factors involved in IBC progression, the role of adipocytes remains unclear. Cancer-associated adipose tissue (CAAT) expresses a variety of adipokines, which contribute to tumorigenesis and the regulation of cancer stem cell (CSC). This research investigated the potential effect of the secretome of CAAT explants from patients with BC on the progression and metastasis of the disease.MethodsThis study established an ex-vivo culture of CAAT excised from IBC (n = 13) vs. non-IBC (n = 31) patients with obesity and profiled their secretome using a cytokine antibody array. Furthermore, the quantitative PCR (qPCR) methodology was used to validate the levels of predominant cytokines at the transcript level after culture in a medium conditioned by CAAT. Moreover, the impact of the CAAT secretome on the expression of epithelial-mesenchymal transition (EMT) and cells with stem cell (CSC) markers was studied in the non-IBC MDA-MB-231 and the IBC SUM-149 cell lines. The statistical differences between variables were evaluated using the chi-squared test and unpaired a Student’s t-test.ResultsThe results of cytokine array profiling revealed an overall significantly higher level of a panel of 28 cytokines secreted by the CAAT ex-vivo culture from IBC patients with obesity compared to those with non-IBC. Of note, interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemo-attractant protein 1 (MCP-1) were the major adipokines secreted by the CAAT IBC patients with obesity. Moreover, the qPCR results indicated a significant upregulation of the IL-6, IL-8, and MCP-1 mRNAs in CAAT ex-vivo culture of patients with IBC vs. those with non-IBC. Intriguingly, a qPCR data analysis showed that the CAAT secretome secretions from patients with non-IBC downregulated the mRNA levels of the CD24 CSC marker and of the epithelial marker E-cadherin in the non-IBC cell line. By contrast, E-cadherin was upregulated in the SUM-149 cell.ConclusionsThis study identified the overexpression of IL-6, IL-8, and MCP-1 as prognostic markers of CAAT from patients with IBC but not from those with non-IBC ; moreover, their upregulation might be associated with IBC aggressiveness via the regulation of CSC and EMT markers. This study proposed that targeting IL-6, IL-8, and MCP-1 may represent a therapeutic option that should be considered in the treatment of patients with IBC.

Associations between adipokines and atrial fibrillation: A systematic review and meta-analysis

AimsAlthough overweight and obesity are associated with increased risk of atrial fibrillation (AF), the underlying mechanisms are not well characterised. Recent data suggest that this link may be partly due to abnormal adipose tissue-derived cytokines or adipokines. However, this relationship is not well clarified. To evaluate the association between adipokines and AF in a systematic review and meta-analysis. Data synthesisPubMed, Embase, and Web of Science Core Collection were searched from inception through 1st March 2021. Studies were included if they reported any adipokine and AF, with their quality assessed using the Newcastle-Ottawa scale. Data were independently abstracted, with unadjusted and multivariable adjusted estimates pooled in a random-effects meta-analysis. Data are presented for overall prevalent or incident AF and AF subtypes (paroxysmal, persistent, or non-paroxysmal AF). A total of 34 studies, with 31,479 patients, were included. The following adipokines were significantly associated with AF in the pooled univariate data — apelin (risk ratio for prevalent AF: 0.05 [0.00–0.50], p = 0.01; recurrent AF: 0.21 [0.11–0.42], p < 0.01) and resistin (incident AF: 2.05 [1.02–4.1], p = 0.04; prevalent AF: 2.62 [1.78–3.85], p < 0.01). Pooled analysis of multivariable adjusted effect size estimates showed adiponectin as the sole independent predictor of AF incidence (1.14 [1.02–1.27], p = 0.02). Moreover, adiponectin was associated with non-paroxysmal AF (persistent AF: 1.45 [1.08–1.94, p = 0.01; non-paroxysmal versus paroxysmal AF: 3.14 [1.87–5.27, p < 0.01). ConclusionsAdipokines, principally adiponectin, apelin, and resistin, are associated with the risk of atrial fibrillation. However, the association is not seen after multivariate adjustment, likely reflecting the lack of statistical power. Future research should investigate these relationships in larger prospective cohorts and how they can refine AF monitoring strategies. PROSPERO IDCRD42020208879.

1391. Body Mass Index and Leptin Levels at Different Stages of the Tuberculosis Spectrum

BackgroundLeptin is an adipose tissue-derived cytokine that plays a role in energy regulation and immune functions. High leptin levels and obesity have been associated with decreased risk of developing active TB. We aimed to characterize the association between body mass index (BMI) and leptin levels in patients at different stages of tuberculosis (TB).MethodsData from a cross-sectional cardiovascular risk study of 40 to 70 years old individuals enrolled in Lima, Peru, and Cincinnati, US, were analyzed. Four categories based on TB and treatment status were defined: no TB infection (QuantiFERON-TB test negative; n= 31), latent TB infection (LTBI; QuantiFERON-TB test positive; n= 43), active TB on treatment (in the continuation TB treatment phase; n= 30), and post-TB (within one year of TB treatment completion; n=16). BMI and plasma leptin levels were compared among the four groups using the Kruskal-Wallis test, followed by Dunn’s multiple comparison test if differences were found in the Kruskal-Wallis test. Multivariate ordered logistic regression models were used to assess factors associated with leptin levels, adjusted for potential confounders.ResultsThe median age was 53 years, and 51% were female. BMI was different between study groups (p< 0.01), with LTBI individuals having the highest BMI compared to other groups; see Figure 1A. Leptin levels were marginally low in the group with active TB on treatment, but no significant differences were found between groups (p=0.44; see Figure 1B). In multivariate analysis, leptin was associated with female sex (OR 23, 95%CI, 9-58), BMI (OR, 1.5, 95%CI, 1.2-1.7), and coronary plaque ≥25% stenosis (OR, 0.29, 95%CI, 0.08-0.99). Body mass index (BMI) and plasma leptin levels in participants with negative QuantiFERON-TB test (QFN-), latent tuberculosis infection (LTBI), active tuberculosis on treatment (ATBT), and post-TB treatment (TB-treated). Significance was determined using the Kruskal-Wallis test, followed by Dunn’s multiple comparison test if the Kruskal- Wallis test p-value was <0.05.ConclusionLTBI individuals had a higher BMI compared to persons with active TB on treatment and post-TB. Higher leptin levels were associated with higher BMI, but we found no association between leptin and TB status in our cohort.Disclosures All Authors: No reported disclosures

Metabolic perturbations in fibrosis disease.

Metabolic changes occur in all forms of disease but their impact on fibrosis is a relatively recent area of interest. This review provides an overview of the major metabolic pathways, glycolysis, amino acid metabolism and lipid metabolism, and highlights how they influence fibrosis at a cellular and tissue level, drawing on key discoveries in dermal, renal, pulmonary and hepatic fibrosis. The emerging influence of adipose tissue-derived cytokines is discussed and brings a link between fibrosis and systemic metabolism. To close, the concept of targeting metabolism for fibrotic therapy is reviewed, drawing on lessons from the more established field of cancer metabolism, with an emphasis on important considerations for clinical translation.

Circulating Levels of Visceral Adipose Tissue-Derived Serine Protease Inhibitor (Vaspin) Appear as a Marker of Musculoskeletal Pain Disability.

Musculoskeletal pain (MSP), specifically low back pain (LBP), is often associated with several adipose tissue-derived cytokines (adipokines) and body composition, but their correlations with the LBP-related disability/severity phenotypes remain poorly understood. In this cross-sectional study, two self-reported validated questionnaires were used to collect back pain and disability data in an ethnically homogeneous family-based population sample (N = 1078). Plasma levels of relatively new adipokines, vaspin and adipsin, were detected by ELISA. Body composition parameters, including fat, skeletal muscle mass, extracellular water (ECW), and others were assessed through bioelectrical impedance analysis (BIA) technology. Statistical analysis was conducted, accounting for the familial composition of the sample. The multiple regression analyses with four LBP-related phenotypes as dependent variables consistently showed, for the first time, the significant associations with vaspin levels, regardless of other covariates. The odds ratios (OR)/SD ranged between 1.24 (95%CI = 1.03–1.50) and 1.33 (95%CI = 1.07–1.64), depending on the LBP phenotype. Among the tested body composition covariates, only ECW levels displayed consistent and highly significant associations with all tested LBP phenotypes (OR from 1.43, 95%CI = 1.14–1.79 to 1.68, 95%CI = 1.26–2.24). The results clearly suggest that circulating concentrations of vaspin and ECW levels could serve as biomarkers of MSP/LBP severity and complications.

Adiponectin receptor 1 gene is potentially associated with severity of postoperative pain but not cancer pain.

Adiponectin is an adipose tissue-derived cytokine that exerts its antiinflammatory effects by binding to 2 adiponectin receptors, adiponectin receptor 1 (ADIPOR1) and adiponectin receptor 2 (ADIPOR2). However, the role of these adiponectin receptors on inflammatory pain remains unclear. We investigated the association between single nucleotide polymorphisms (SNPs) of these genes and inflammatory pain, such as postoperative pain and cancer pain.We analyzed 17 SNPs of the ADIPOR1 gene and 27 SNPs of the ADIPOR2 gene in 56 adult patients with postlaparotomy pain. We compared these genotypes with pain intensity and opioid consumption, adjusting for multiple testing. We analyzed the genotypes of 88 patients with cancer pain and examined the association of the relevant SNP(s) with pain intensity and opioid consumption.One variant of the ADIPOR1 gene (rs12045862) showed significant association with postoperative pain intensity; patients with minor allele homozygote (n = 7) demonstrated significantly worse pain intensity than that of combined patient group exhibiting major allele homozygote or the heterozygote (n = 49; Mann-Whitney test, P < .00002), although their opioid consumptions were comparable. Cancer pain intensity between minor allele homozygote patients (n = 7) and other 2 genotype patients (n = 81) were comparable.The rs12045862 SNP of the ADIPOR1 gene was associated with postoperative pain but not cancer pain. This might result from functional alteration of the ADIPOR1 signalling pathways, which influence the inflammatory process. ADIPOR1 may be a novel potential target for developing analgesics of postoperative pain.

Review of obesity and periodontitis: an epidemiological view.

Obesity and periodontitis are among the most common non-communicable diseases, and epidemiological studies report the influence of obesity in the onset and progression of periodontitis. Data indicate that increased body mass index, waist circumference, percentage of subcutaneous body fat, and serum lipid levels are associated with increased risk to develop periodontitis. The underlying biological mechanisms of this association involve adipose tissue-derived cytokines, such as tumour necrosis factor-α and interleukin-6, which affect whole-body metabolism and contribute to the development of a low-grade systemic inflammation. Multiple studies report a positive association between these two diseases across diverse populations. Obesity does not appear to impair the success of periodontal therapy. However, currently available evidence is variable and therefore inconclusive. Despite the limited evidence about recommendations on treatment planning, oral healthcare professionals need to be aware of the complexity of obesity to counsel their patients about the importance of maintaining healthy body weight and performing good oral hygiene procedures.

Implications of resistin in type 2 diabetes mellitus and coronary artery disease: Impairing insulin function and inducing pro‐inflammatory cytokines

Diabetes mellitus is a metabolic and chronic disorder, which is very common all over the world. Many genetic and nongenetic factors are involved in the development of type 2 diabetes mellitus (T2DM). Meanwhile, the resistin gene is an important candidate in the pathogenesis of this complex condition. High levels of transcription of the resistin gene are associated with inflammation, insulin resistance, initiation and development of T2DM and atherosclerosis progression through induction of secretion of bioactive materials from adipocytes. Releasing adipose tissue-derived inflammatory cytokines is associated with inflammatory processes activation, which causes inhibition of insulin action via interference with insulin signaling, suchthat these disorders can contribute to insulin resistance. With the direct effect of resistin and other inflammatory mediators on vascular endothelial cells and arterial walls, the expression of cell adhesion molecules is increased. This process can lead to atherosclerosis and will result in coronary artery disease (CAD). In this review, we will explore the effects of resistin on inflammation and insulin resistance that may lead to type 2 diabetes and CAD.

Bone marrow adipose tissue-derived stem cell factor mediates metabolic regulation of hematopoiesis.

Hematopoiesis is dynamically regulated by metabolic cues in homeostatic and stressed conditions; however, the cellular and molecular mechanisms mediating the metabolic sensing and regulation remain largely obscure. Bone marrow adipose tissue remodels in various metabolic conditions and has been recently proposed as a niche for hematopoietic stem cells after irradiation. Here, we investigated the role of marrow adipose tissue-derived hematopoietic cytokine stem cell factor in unperturbed hematopoiesis by selectively ablating the Kitl gene from adipocytes and bone marrow stroma cells using Adipoq-Cre and Osx1-Cre, respectively. We found that both Adipoq-Kitl knockout (KO) and Osx1-Kitl KO mice diminished hematopoietic stem and progenitor cells and myeloid progenitors in the bone marrow and developed macrocytic anemia at the steady-state. The composition and differentiation of hematopoietic progenitor cells in the bone marrow dynamically responded to metabolic challenges including high fat diet, β3-adrenergic activation, thermoneutrality, and aging. However, such responses, particularly within the myeloid compartment, were largely impaired in Adipoq-Kitl KO mice. Our data demonstrate that marrow adipose tissue provides stem cell factor essentially for hematopoiesis both at the steady state and upon metabolic stresses.

Adipose tissue-derived cytokines and their correlations with clinical characteristics in Vietnamese patients with type 2 diabetes mellitus

BackgroundAdipokines are involved in the pathogenesis of metabolic disorders including obesity and type 2 diabetes mellitus (T2DM). This study investigates the levels of leptin, resistin, visfatin, secreted frizzled-related protein 5 (SFRP5), monocyte chemoattractant protein-1 (MCP-1) and retinol-binding protein 4 (RBP4) and their correlations with clinical parameters of overweight and T2DM.MethodsWe recruited overweight 50 patients with T2DM, 88 non-overweight patients with T2DM, 29 overweight and 100 non-overweight individuals devoid of T2DM for this study. The levels of studied adipokines were measured by enzyme-linked immunosorbent assay and correlated with clinical parameters.ResultsThe levels of MCP-1 and SFRP5 were decreased while visfatin and RBP4 levels were increased in patients with T2DM compared to those in the control individuals (P < 0.01). Among patients with T2DM, leptin and resistin levels were higher while RBP4 levels were lower in patients with overweight T2DM compared to those in patients with non-overweight T2DM (P < 0.0001, 0.019 and 0.05, respectively). Leptin and MCP-1 levels were correlated with HOMA-IR, QUICKI and HOMA-β. Leptin/MCP-1 ratio was correlated with insulin levels, HOMA-IR and HOMA-β indexes. Resistin/RBP4, visfatin/MCP-1 and MCP-1/RBP4 ratios were strongly correlated with the levels of fasting glucose, HbA1c and HOMA-β. In addition, ROC curve analyses indicated a diagnostic potential of resistin/RBP4 and MCP-1/RBP4 indexes for T2DM (AUC = 0.81 and 0.83, respectively) and β-cell function (AUC = 0.76 and 0.74, respectively).ConclusionsAdipokines (leptin, resistin, visfatin, SFRP5, MCP-1, and RBP4) are associated with overweight and T2DM and may serve as a potential prognostic marker and therapeutic intervention for overweight-related T2DM.

Evaluation of serum adiponectin levels in diabetic nephropathy

IntroductionDiabetic nephropathy is one of the major microvascular complications of diabetes mellitus. Adiponectin is an adipose tissue-derived cytokine that was identified in a human adipose tissue cDNA library. Serum adiponectin levels are found to be reduced in various pathological states including obesity, diabetes mellitus, ischaemic heart disease and arteriosclerosis obliterans and elevated in end stage renal diseases. Objective: to assess the level of plasma adiponectin as an early predictor of microvascular complications in patients with type 2 diabetes mellitus. Methods44 patients with type 2 diabetes recruited from outpatient diabetes clinic in Kasr Alainy hospital. All patients were subjected to full laboratory work-up including: Fasting blood glucose and Post prandial blood glucose, Glycated haemoglobin A1C, Serum creatinine, Serum total cholesterol, Triglycerides, Low density lipoprotein, High density lipoprotein, C-reactive protein titre, serum adiponectin and Urinary albumin/creatinine (UAC) ratio. ResultsThe present study demonstrated that serum adiponectin concentrations had significant positive correlation with UAC ratio (r = 0.534, p = 0.0001). Adiponectin levels showed significant positive correlation in patients with diabetes and hypertension with microalbumiuria (p = .001) or normoalbumiuria (p = 0.004). ConclusionSerum adiponectin level can be a good predictor of diabetic nephropathy in patients with type 2 diabetes mellitus.

Adipose tissue-derived cytokines, CTRPs as biomarkers and therapeutic targets in metabolism and the cardiovascular system

Adipose tissue-derived cytokines, CTRPs as biomarkers and therapeutic targets in metabolism and the cardiovascular system

Biomechanics, obesity, and osteoarthritis. The role of adipokines: When the levee breaks.

Osteoarthritis is a high-incidence painful and debilitating disease characterized by progressive degeneration of articular joints, which indicates a breakdown in joint homeostasis favoring catabolic processes. Biomechanical loading, associated with inflammatory and metabolic imbalances of joint, strongly contributes to the initiation and progression of the disease. Obesity is a primary risk factor for disease onset, and mechanical factors increased the risk for disease progression. Moreover, inflammatory mediators, in particular, adipose tissue-derived cytokines (better known as adipokines) play a critical role linking obesity and osteoarthritis. The present article summarizes the knowledge about the role of adipokines in cartilage and bone function, highlighting their contribution to the imbalance of joint homeostasis and, consequently, pathogenesis of osteoarthritis. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:594-604, 2018.

Cytokine profiles in overweight and obese subjects and normal weight individuals matched for age and gender.

Background Obesity is associated with a state of systemic inflammation, mediated by adipose tissue-derived cytokines that may also have metabolic effects, including an effect on insulin resistance. The aim of this study was to compare the serum profile of pro- and anti-inflammatory cytokines in obese and non-obese subjects. Methods A total of 242 subjects who were either overweight or obese (body mass index [BMI] ≥ 25 kg/m2) and non-obese subjects (body mass index <25 kg/m2), were recruited in Mashhad in northeastern Iran. The concentrations of serum interleukin-1α, -1β, -2, -4, -6, -8 and -10 (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8 and IL-10), were measured in all subjects, together with serum vascular endothelial growth factor, interferon-γ, epidermal growth factor, monocyte chemoattractant protein-1 and tumour necrosis factor-α. Results The groups differed significantly with respect to measures of adiposity and fasted lipid profile. Serum pro-inflammatory cytokines interferon-γ and interleukin-1α, and anti-inflammatory cytokines, interleukin-10, and epidermal growth factor were significantly different between obese and non-obese individuals, as was serum high-sensitivity C-reactive protein. Multivariate regression showed that waist circumference was significantly and independently related to serum monocyte chemoattractant protein-1concentrations ( P = 0.001). Conclusion Despite significant differences in several cytokines between the groups, only monocyte chemoattractant protein-1appeared to be independently related to a measure of adiposity in this population sample from Iran.

A high-fat diet containing lard accelerates prostate cancer progression and reduces survival rate in mice: possible contribution of adipose tissue-derived cytokines.

To examine the effects of high-fat diet (HFD) containing lard on prostate cancer development and progression and its underlying mechanisms, transgenic adenocarcinoma mouse prostate (TRAMP) and TRAMP-C2 allograft models, as well as in vitro culture models, were employed. In TRAMP mice, HFD feeding increased the incidence of poorly differentiated carcinoma and decreased that of prostatic intraepithelial neoplasia in the dorsolateral lobes of the prostate, which was accompanied by increased expression of proteins associated with proliferation and angiogenesis. HFD feeding also led to increased metastasis and decreased survival rate in TRAMP mice. In the allograft model, HFD increased solid tumor growth, the expression of proteins related to proliferation/angiogenesis, the number of lipid vacuoles in tumor tissues, and levels of several cytokines in serum and adipose tissue. In vitro results revealed that adipose tissue-conditioned media from HFD-fed mice stimulated the proliferation and migration of prostate cancer cells and angiogenesis compared to those from control-diet-fed mice. These results indicate that the increase of adipose tissue-derived soluble factors by HFD feeding plays a role in the growth and metastasis of prostate cancer via endocrine and paracrine mechanisms. These results provide evidence that a HFD containing lard increases prostate cancer development and progression, thereby reducing the survival rate.

Adipocentric View of the Cardiometabolic Alternations Related to Abdominal Obesity

Body fat distribution patterns in humans are heterogeneous and result from regional differences in intrinsic properties of adipose cells as well as local hormonal effects. Under chronic overfeeding conditions, adipose tissue expansion in a given compartment occurs by adipocyte hypertrophy (enlargement of existing adipocytes through triglyceride synthesis), and/or adipocyte hyperplasia (generation of new adipocytes through differentiation of preadipocytes). Visceral adipocytes (e.g. omental fat cells) are efficient for hypertrophy through lipid storage and show high lipolytic responsiveness, whereas subcutaneous cells have a higher capacity for hyperplasia. Our results demonstrate that visceral adipocyte hypertrophy and high diacylglycerol acyltransferase activity are independently related to hypertriglyceridemia and triglyceride enrichment of circulating lipoproteins. Moreover, low capacity for adipogenic differentiation of preadipocytes in the subcutaneous fat compartment is a significant predictor of excess visceral adipose tissue accumulation, visceral adipocyte hypertrophy, triglyceride enrichment of lipoproteins and fasting hyperglycemia. Adipose tissue-derived cytokines and immune cells infiltrating adipose tissues also mediate the link between visceral obesity and cardiometabolic alterations increasing type 2 diabetes and cardiovascular disease risk. These inflammatory phenotypes are also observed in patients with visceral adipocyte hypertrophy when compared to those who predominantly exhibit hyperplasic adipose tissue expansion. Overall, in individuals with elevated cardiometabolic risk, adipose tissue function impairments include adipocyte hypertrophy, impaired adipogenesis, low free fatty acid uptake, reduced triglyceride synthesis, resistance to the inhibitory effect of insulin on lipolysis, immune cell infiltration and inflammatory cytokine secretion. These alterations collectively reflect reduced storage capacity of fat tissues and contribute to systemic metabolic perturbation.

The role of adipocytokines in the pathogenesis of knee joint osteoarthritis.

Osteoarthritis (OA) is one of the most common causes of musculoskeletal disability in the world. Traditionally, it has been thought that obesity contributes to the development and progression of OA by increased mechanical load of the joint structures. Nevertheless, studies have shown that adipose tissue-derived cytokines (adipocytokines) are a possible link between obesity and OA. Furthermore, according to recent findings, not only articular cartilage may be the main target of these cytokines but also the synovial membrane, subchondral bone and infrapatellar fat pad may be encompassed in the process of degradation. This review presents the most recent reports on the contribution of adipocytokines to the knee joint cartilage degradation, osteophyte formation, infrapatellar fat pad alterations and synovitis.

Obesity and cancer

The incidence of obesity in the western world has increased dramatically during recent decades. Epidemiological data suggest that obesity is associated with an increased risk of several but not all types of cancers, with clear sex-specific differences. The underlying mechanisms are still a matter of debate. This review focuses on the potential factors linking obesity to cancer. Current experimental evidence suggests that insulin resistance and a chronic, subclinical inflammation in the visceral fat are the major metabolic events causing alterations in the levels of insulin, glucose, free fatty acids, insulin-like growth factor 1 (IGF-1) and 2, adipose tissue-derived proinflammatory cytokines and other bioactive molecules, such as adipokines (e.g. leptin and adiponectin), vascular endothelial growth factor (VEGF), sex hormones, gut microbiota and secondary bile acids. All these factors may act directly or indirectly on the tumor microenvironment to drive tumor progression via stimulation of cell survival/antiapoptosis, cell proliferation, angiogenesis and invasion/metastasis of the cancer cells. Therapeutic strategies that target dysfunctional or inflamed fat and have been shown to benefit patients include bariatric surgery, while other cell or hormone-directed interventions, such as conversion of visceral fat macrophages to an anti-inflammatory M2 phenotype or the pharmacological modulation of serum adipokine levels are still theoretical and need to be clinically evaluated for their ability to successfully treat or prevent obesity-related cancers.