Dysregulation Of Adipokines Research Articles

Kidney consequences of obesity.

Herein, we review the devastating consequences of the worldwide obesity epidemic on kidney health and outcomes. We submit that the obesity epidemic is the most pressing public health crisis facing the nephrology community today. A historical approach has been undertaken, wherein major breakthroughs in the recognition and understanding of obesity-related kidney disease (ORKD) are highlighted. We begin with a description of the worldwide obesity epidemic followed by an account of the discovery and characterization of ORKD. A detailed summary of the pathophysiology of ORKD disease is presented, wherein we set forth the following two propositions: first, ORKD is due to a maladaptive response to caloric surplus; and second, this maladaptive response causes kidney damage via hemodynamic (hyperfiltration), hormonal (adipokine dysregulation), and lipotoxic pathways. Each of these pathways is described, with particular emphasis on the relatively recent discovery that the final stage of cellular injury in ORKD is mitochondrial oxidative damage. The prevention and treatment of ORKD are then discussed, including environmental, behavioral, pharmacologic, and surgical options. Finally, we conclude with suggestions for future research to improve early recognition and treatment of ORKD.

Adipokines and Cardiometabolic Heart Failure with Preserved Ejection Fraction: A State-of-the-Art Review.

Cardiometabolic heart failure with preserved ejection fraction (HFpEF) is largely driven by obesity-related factors, including adipokines and bioactive peptides primarily secreted by the adipose tissue, such as leptin, adiponectin, and resistin. These molecules link metabolic dysregulation to cardiovascular dysfunction, influencing HFpEF progression and patient outcomes Methods: A comprehensive literature search was conducted in PubMed up to 20 November 2024, using keywords and MeSH terms, such as "HFpEF", "adipokines", "leptin", "adiponectin", and "resistin", yielding 723 results. Boolean operators refined the search, and reference lists of key studies were reviewed. After screening for duplicates and irrelevant studies, 103 articles were included, providing data on adipokines' roles in HFpEF pathophysiology, biomarkers, and therapeutic implications. Both preclinical and clinical studies have demonstrated that adipokines play a role in modulating cardiovascular function, thereby contributing to the development of cardiometabolic HFpEF. Leptin promotes myocardial hypertrophy, fibrosis, endothelial dysfunction, and inflammation, though contradictory evidence suggests potential cardioprotective roles in subgroups like obese African American women. Adiponectin generally offers protective effects but presents a paradox, where elevated levels may correlate with worse outcomes, which may reflect either a compensatory response to cardiac dysfunction or a maladaptive state characterized by adiponectin resistance. Resistin is associated with increased cardiovascular risk through pro-inflammatory and pro-fibrotic effects, though its role in HFpEF requires further clarification. Other adipokines, like retinol-binding protein 4 and omentin-1, have emerged as potential contributors. Despite growing insights, clinical translation remains limited, underscoring a significant gap between experimental evidence and therapeutic application. Future research should focus on targeted interventions that modulate adipokine pathways to potentially improve HFpEF outcomes. Innovative treatment strategies addressing underlying metabolic disturbances and adipokine dysregulation are essential for advancing the management of this challenging condition.

Exploring the Role of Adipose Tissue Dysregulation in Vitiligo Pathogenesis: A Body Composition Analysis.

Vitiligo is a commonly acquired pigmentary disease characterized by the progressive destruction of melanocytes. The role of adipose tissue in vitiligo remains unclear. To investigate the role of adipose tissue in the pathogenesis of vitiligo, 50 patients newly diagnosed with vitiligo and 40 age- and sex-matched healthy controls were enrolled, and fat mass and distribution using dual-energy X-ray absorptiometry (DXA) and serum adipokine levels using enzyme-linked immunosorbent assay were assessed. The trunk and whole-body fat mass and the trunk/limb fat mass ratio were significantly higher in patients with vitiligo. Higher leptin and resistin levels and lower adiponectin levels were observed. Positive correlation of the trunk fat mass index with vitiligo area scoring index scores (r = 0.38, p = 0.0071) was found. Additionally, plasma adiponectin levels were negatively correlated with vitiligo disease activity scores (r = -0.307, p < 0.05). Receiver operating characteristic curve analysis showed that the percentage of limb lean tissue mass, trunk/limb fat mass ratio, and serum adipokine levels achieved a high area under the curve score for distinguishing patients with vitiligo from healthy controls. In conclusion, the incidence of central obesity and adipokine dysregulation was higher in patients with vitiligo. The potential role of adipose tissue in the pathogenesis of vitiligo should be emphasized.

Serum Leucine-Rich Alpha-2 Glycoprotein 1 Levels in Patients with Lipodystrophy Syndromes.

Serum concentrations of leucine-rich alpha-2 glycoprotein 1 (LRG1) are elevated in several cardio-metabolic and inflammatory diseases. LRG1 also plays an important role in the development of hepatic steatosis and insulin resistance. In lipodystrophies (LDs), severe cardio-metabolic complications can be observed. The dysregulation of several adipokines plays a significant role in the clinical manifestation of this syndrome. To date, there have been no studies of LRG1 levels in non-HIV-LD patients. We performed a cross-sectional analysis of LRG1 serum levels in 60 patients with non-HIV-associated LD and in 60 age-, sex-, and BMI-matched healthy controls. Furthermore, we investigated the gene expression of Lrg1 in a mouse model of generalised LD. No significant difference was found in the median concentration of LRG1 serum levels between LD patients (18.2 ng/L; interquartile range 8.3 ng/L) and healthy controls (17.8 ng/L; interquartile range 11.0 ng/L). LRG1 serum concentrations correlated positively with CRP serum levels (p < 0.001). Lrg1 mRNA expression was downregulated in the adipose tissue, whereas in the liver, no difference in Lrg1 expression between LD and wild-type mice was detected. In summary, circulating levels of LRG1 are associated with low-grade inflammation but cannot distinguish between patients with LD and controls.

Novel perspectives on the link between obesity and cancer risk: from mechanisms to clinical implications.

Existing epidemiologic and clinical studies have demonstrated that obesity is associated with the risk of a variety of cancers. In recent years, an increasing number of experimental and clinical studies have unraveled the complex relationship between obesity and cancer risk and the underlying mechanisms. Obesity-induced abnormalities in immunity and biochemical metabolism, including chronic inflammation, hormonal disorders, dysregulation of adipokines, and microbial dysbiosis, may be important contributors to cancer development and progression. These contributors play different roles in cancer development and progression at different sites. Lifestyle changes, weight loss medications, and bariatric surgery are key approaches for weight-centered, obesity-related cancer prevention. Treatment of obesity-related inflammation and hormonal or metabolic dysregulation with medications has also shown promise in preventing obesity-related cancers. In this review, we summarize the mechanisms through which obesity affects the risk of cancer at different sites and explore intervention strategies for the prevention of obesity-associated cancers, concluding with unresolved questions and future directions regarding the link between obesity and cancer. The aim is to provide valuable theoretical foundations and insights for the in-depth exploration of the complex relationship between obesity and cancer risk and its clinical applications.

The association between adipokines dysregulation and the occurrence of atrial fibrillation and obese patients, is it relevant?

Atrial fibrillation (AF) is the most common arrhythmia, affecting approximately 33.5 millions of people worldwide. Unfortunately, the prevalence of this arrhythmia will increase within the following two decades, resulting in a higher mortality rate and a higher economic burden for public health services. Obesity, specifically central obesity, plays an essential role in developing AF by increasing pericardial fat and epicardial adipose tissue thickness, generating a chronic inflammation state where dysregulation of the serum concentration of several proinflammatory proteins occurs and indirectly promotes AF. Therefore, recent research has focused on analyzing the circulating concentration of different molecules, including pro and anti-inflammatory adipokines, and their association with AF. Herein, we review several studies addressing the association of adipokines with the onset or recurrence of AF to establish such association as a potential biomarker for the prevention or adequate treatment of this arrhythmia. We concluded that the insight into this topic is very controversial and needs further research.

A Cross-Sectional Study: Systematic Quantification of Chemerin in Human Cerebrospinal Fluid.

Dysregulation of adipokines is considered a key mechanism of chronic inflammation in metabolic syndrome. Some adipokines affect food intake by crossing the blood/brain barrier. The adipokine chemerin is associated with metabolic syndrome, cardiovascular diseases and immune response. Little is known about chemerin's presence in cerebrospinal fluid (CSF) and its ability to cross the blood/CSF barrier. We quantified chemerin levels in paired serum and CSF samples of 390 patients with different neurological diagnoses via enzyme-linked immunosorbent assay (ELISA). Correlation analyses of serum and CSF chemerin levels with anthropometric, serum and CSF routine parameters were performed. Overweight patients exhibited higher chemerin levels in serum and CSF. Chemerin CSF levels were higher in men. Chemerin levels in serum were associated with BMI (body mass index) and CRP (C-reactive protein). Chemerin levels in CSF were associated with age. Neurological diseases affected chemerin levels in CSF. The chemerin CSF/serum ratio was calculated as 96.3 ± 36.8 × 10-3 for the first time. Our data present a basis for the development of standard values for chemerin quantities in CSF. CSF chemerin levels are differentially regulated in neurological diseases and affected by BMI and sex. Chemerin is able to cross the blood/CSF barrier under physiological and pathophysiological conditions.

Adipokine dysregulation as an underlying pathology for diffuse ectopic ossification of spinal posterior longitudinal ligament in patients with obesity

BACKGROUND CONTEXTGrowing evidence suggests that obesity is implicated in the progression of heterotopic ossification of the posterior longitudinal ligament of the spine (OPLL), a major cause of myelopathy in Asians. However, it remains unclear whether dysregulation of adipokine production due to fat accumulation contributes to OPLL progression. PURPOSETo determine whether adipose-derived biochemical signals are associated with OPLL development or severity. STUDY DESIGN/SETTINGA nationwide, multicenter, case-control study. PATIENT SAMPLEPatients with symptomatic thoracic OPLL (T-OPLL) who received treatment between June 2017 and March 2021 and 111 controls without OPLL. OUTCOME MEASURESOPLL severity index based on whole-spine computed tomography. METHODSSerum concentrations of adipokines, including leptin (Lep), tumor necrosis factor α (TNFα), and adiponectin (Adpn), as well as the Adpn/Lep ratio—an indicator of adipokine production dysregulation—were compared between the multiple-region OPLL and the single-region OPLL groups. Regression analysis was performed to examine the correlation between adipokine concentrations and OPLL severity index, which was calculated using whole-spine computed tomography images of 77 patients with T-OPLL within 3 years of onset. Using propensity score matching, the adipokine profiles of 59 patients with T-OPLL were compared with those of 59 non-OPLL controls. RESULTSPatients with multiple-region OPLL exhibited a higher body mass index (BMI), lower serum Adpn/Lep ratio, and higher serum concentration of osteocalcin (OCN) than those with single-region OPLL. The OPLL severity index exhibited a weak positive correlation with BMI and serum Lep levels and a weak negative correlation with the Adpn/Lep ratio. Serum TNFα and OCN concentrations were significantly higher in patients with T-OPLL than in controls with similar age, sex, and BMI. CONCLUSIONSPatients with diffuse OPLL over the entire spine are often metabolically obese with low Adpn/Lep ratios. In patients with OPLL, TNFα and OCN serum concentrations were essentially elevated regardless of obesity, suggesting a potential association with OPLL development. Considering the absence of therapeutic drugs for OPLL, the findings presented herein offer valuable insights that can aid in identifying therapeutic targets and formulating strategies to impede its progression.

Medicinal Plant Extracts against Cardiometabolic Risk Factors Associated with Obesity: Molecular Mechanisms and Therapeutic Targets.

Obesity has increasingly become a worldwide epidemic, as demonstrated by epidemiological and clinical studies. Obesity may lead to the development of a broad spectrum of cardiovascular diseases (CVDs), such as coronary heart disease, hypertension, heart failure, cerebrovascular disease, atrial fibrillation, ventricular arrhythmias, and sudden cardiac death. In addition to hypertension, there are other cardiometabolic risk factors (CRFs) such as visceral adiposity, dyslipidemia, insulin resistance, diabetes, elevated levels of fibrinogen and C-reactive protein, and others, all of which increase the risk of CVD events. The mechanisms involved between obesity and CVD mainly include insulin resistance, oxidative stress, inflammation, and adipokine dysregulation, which cause maladaptive structural and functional alterations of the heart, particularly left-ventricular remodeling and diastolic dysfunction. Natural products of plants provide a diversity of nutrients and different bioactive compounds, including phenolics, flavonoids, terpenoids, carotenoids, anthocyanins, vitamins, minerals, fibers, and others, which possess a wide range of biological activities including antihypertensive, antilipidemic, antidiabetic, and other activities, thus conferring cardiometabolic benefits. In this review, we discuss the main therapeutic interventions using extracts from herbs and plants in preclinical and clinical trials with protective properties targeting CRFs. Molecular mechanisms and therapeutic targets of herb and plant extracts for the prevention and treatment of CRFs are also reviewed.

An Increasing Triglyceride-Glucose Index Is Associated with a Pro-Inflammatory and Pro-Oxidant Phenotype.

Background/Objectives: Insulin resistance is crucial in the pathogenesis of Metabolic Syndrome (MetS), type 2 diabetes mellitus (T2DM) and premature atherosclerotic cardiovascular disease (ASCVD). The triglyceride-glucose index (TyG index), a validated measure of insulin resistance, also predicts MetS, T2DM, the severity of albuminuria and ASCVD. There are scant data providing mechanistic insights into these sequalae. Accordingly, we investigated the relationship between the TyG index and biomarkers of inflammation, oxidative stress, free fatty acid (FFA) levels and adipokine dysregulation in a cohort comprising both controls and patients with nascent MetS. Methods: Participants (n = 102) included 59 patients with MetS and 43 controls. People with diabetes, ASCVD, smoking and macro-inflammation were excluded. Fasting blood was obtained for both plasma and monocyte isolation. Results: Receiver Operating Characteristic (ROC) curve analysis revealed that the TyG index was an excellent predictor of MetS with an area under the curve of 0.87, and it correlated with both hepatic and adipose tissue insulin resistance. Both serum RBP-4 levels and non-HDL cholesterol increased significantly over tertiles of the TyG index. Based on the TyG index tertiles and/or correlations, oxidized LDL, nitrotyrosine, C-reactive protein, endotoxin, chemerin, interleukin-6 levels and monocyte toll-like receptor (TLR)-4 and TLR-2 and their cellular signaling were significantly associated with the TyG index. Conclusions: Increased non-HDL-C and, most importantly, a pro-inflammatory and pro-oxidant state could be advanced as potential mechanisms explaining the increased risk for T2DM and ASCVD with an increasing TyG index.

Current research trends on the effect of diabetes mellitus on rotator cuff tendon healing/tendinopathy.

Rotator cuff tendon tears are a leading cause of shoulder pain. They are challenging to treat, and tendon-bone healing has a high failure rate despite successful surgery. Tendons connect the muscles and bones, which make them important for the body's overall mobility and stability. Metabolic diseases, including diabetes or high blood pressure, can affect the healing process after repair of a damaged tendon. With a global incidence of 9.3%, diabetes is considered as a significant risk factor for rotator cuff tendon healing because it causes structural, inflammatory, and vascular changes in the tendon. However, the mechanisms of how diabetes affects tendon healing remain unknown. Several factors have been suggested, including glycation product accumulation, adipokine dysregulation, increased levels of reactive oxygen species, apoptosis, inflammatory cytokines, imbalanced matrix-metalloproteinase-to-tissue-inhibitor ratio, and impaired angiogenesis and differentiation of the tendon sheath. Despite the effects of diabetes on tendon function and healing, few treatments are available to improve recovery in these patients. This review summarizes the current literature on the pathophysiological changes of the tendon in diabetes and hyperlipidemia. Preclinical and clinical evidence regarding the association between diabetes and tendon healing is presented. Moreover, current approaches to improve tendon healing in patients with diabetes are reviewed.

Adipocines and longevity: connections and paradoxes

Adipose tissue is an active endocrine organ that regulates energy homeostasis throughout the body by releasing hundreds of biologically active substances called adipokines. Dysregulation of adipokines is a key feature of insulin resistance with the development of metabolic syndrome and type 2 diabetes mellitus, which is an age-dependent pathology. In turn, dysregulation of adipokines and insulin resistance are associated with the development of metabolic deficiency and senile asthenia syndrome in older age groups. Previous studies have shown that the absence of insulin resistance and low prevalence of diabetes among centenarians are metabolic prerequisites for increased lifespan, suggesting a possible role for adipokine homeostasis in healthy longevity. Among numerous adipokines, adiponectin is considered a protective factor, showing a negative correlation with major metabolic disorders associated with age and obesity, and a positive association with life expectancy and insulin sensitivity among centenarians. Despite all the apparent protective effects of adiponectin, large-scale epidemiological studies have revealed the opposite aspect of adiponectin as a predictor of all-cause mortality and cardiovascular disease in patients with heart failure as well as kidney disease. In this review, the clinical significance of adiponectin is considered in centenarians from the point of view of the development of the main geriatric syndrome - senile asthenia, as well as cardiovascular risk and mortality.

Adipokines, Vitamin D, and Selected Inflammatory Biomarkers among Parkinson's Disease Patients with and without Dyskinesia: A Preliminary Examination.

Parkinson's disease (PD), a widely recognized neurodegenerative disorder, is characterized by a spectrum of symptoms including motor fluctuations and dyskinesia. Neuroinflammation and dysregulation of adipokines are increasingly implicated in the progression of PD. This preliminary study investigated the levels of inflammatory biomarkers and adipokines, namely interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), C-reactive protein (CRP), visfatin, progranulin, and 25(OH)-vitamin D in 52 PD patients, divided equally between those with and without dyskinesia and 26 healthy controls. Significant differences in the levels of IL-6, TNF-α, visfatin, and progranulin were noted between the groups. Patients with dyskinesia exhibited notably higher IL-6 levels compared to controls, and TNF-α was significantly elevated in both PD patient groups relative to the control group. Additionally, visfatin levels were higher in PD patients without dyskinesia as opposed to those with dyskinesia, and progranulin levels were elevated in the non-dyskinetic PD group compared to controls. The findings highlight the potential role of the examined biomarkers in the pathophysiology of PD. Changes in levels of the tested inflammatory biomarkers and adipokines might be associated with Parkinson's disease and its symptoms such as dyskinesia.

Endoplasmic Reticulum Stress and Its Impact on Adipogenesis: Molecular Mechanisms Implicated.

Endoplasmic reticulum (ER) stress plays a pivotal role in adipogenesis, which encompasses the differentiation of adipocytes and lipid accumulation. Sustained ER stress has the potential to disrupt the signaling of the unfolded protein response (UPR), thereby influencing adipogenesis. This comprehensive review illuminates the molecular mechanisms that underpin the interplay between ER stress and adipogenesis. We delve into the dysregulation of UPR pathways, namely, IRE1-XBP1, PERK and ATF6 in relation to adipocyte differentiation, lipid metabolism, and tissue inflammation. Moreover, we scrutinize how ER stress impacts key adipogenic transcription factors such as proliferator-activated receptor γ (PPARγ) and CCAAT-enhancer-binding proteins (C/EBPs) along with their interaction with other signaling pathways. The cellular ramifications include alterations in lipid metabolism, dysregulation of adipokines, and aged adipose tissue inflammation. We also discuss the potential roles the molecular chaperones cyclophilin A and cyclophilin B play in adipogenesis. By shedding light on the intricate relationship between ER stress and adipogenesis, this review paves the way for devising innovative therapeutic interventions.

Excessive Pregestational Weight and Maternal Obstetric Complications: The Role of Adipokines.

There is a high frequency of overweight and obesity in women of reproductive age. Women who start pregnancy with overweight or obesity have an increased risk of developing maternal obstetric complications such as gestational hypertension, pre-eclampsia, gestational diabetes mellitus, postpartum hemorrhage, and requiring C-section to resolve the pregnancy with a higher risk of C-section surgical site infection. Excessive weight in pregnancy is characterized by dysregulation of adipokines, the functions of which partly explain the predisposition of pregnant women with overweight or obesity to these maternal obstetric complications. This review compiles, organizes, and analyzes the most recent studies on adipokines in pregnant women with excess weight and the potential pathophysiological mechanisms favoring the development of maternal pregnancy complications.

Adiponectin receptor 1 could explain the sex differences in molecular basis of cognitive improvements induced by exercise training in type 2 diabetic rats

Adipokines dysregulation, the main reason for cognitive impairments (CI) induced by diabetes, shows a sex-dependent pattern inherently and in response to exercise. This study aimed to compare the attenuating effect of 8-week high intensity-interval training (HIIT) on type 2 diabetes (T2D)-induced CI between male and female rats with a special focus on adiponectin and leptin. 28 male & 28 female Wistar rats with an average age of 8 weeks were randomly assigned into four groups: control (Con), exercise (EX), Diabetes (T2D), and Type 2 diabetes + exercise (T2D + Ex). Rats in EX and T2D + EX groups performed HIIT for eight weeks (80–100% Vmax, 4–10 intervals). T2D was induced by 2 months of a high-fat diet and a single dose of STZ (35 mg/kg) administration. Leptin and adiponectin levels in serum were measured along with hippocampal expression of leptin and adiponectin receptors, AMP-activated protein kinase (AMPK), dephosphorylated glycogen synthase kinase-3 beta (Dep-GSK3β), Tau, and beta-amyloid (Aβ). Homeostasis model assessments (HOMAs) and quantitative insulin-sensitivity check index (QUICKI) indices were calculated. Our results showed that following T2D, serum levels of APN, and hippocampal levels of adiponectin receptor 1 (APNR1) were higher and HOMA-IR was lower in female than male rats (P < 0.05). However, after 8 weeks of HIIT, hippocampal levels of APNR1 and AMPK as well as QUICKI were lower and hippocampal levels of GSK, Tau, and Aβ were higher in females compared to male rats (P < 0.05). While the risk of CI following T2D was more in male than female rats HIIT showed a more ameliorating effect in male animals with APN1 as the main player.

Dysregulation of adipokines levels among healthy first-degree relatives of type 2 diabetes patients

BackgroundLeptin, adiponectin and its ratio (L/A), as well as adipocyte fatty acid binding protein (A-FABP) have shown association to type 2 diabetes and atherosclerosis. Since first degree relatives (FDR) of type 2 diabetes are known to have higher risks of developing aforementioned diseases, this study aimed to see differences in adipokines profiles between FDR of type 2 diabetes and non-FDR counterpart. MethodsAge, sex and body mass index (BMI)-matched normotensive-normoglycemic subjects, aged 19–39 years with BMI<30 kg/m2, were included in this cross-sectional study. Serum adiponectin, leptin, and A-FABP levels were measured by sandwich ELISA while HOMA-IR was calculated from fasting blood glucose and insulin levels. ResultsOf 116 subjects recruited, there were significant difference of insulin level (6.00 vs 5.00 μIU/mL, P = 0.029) and HOMA-IR (1.27 vs 1.10, P = 0.028). Adiponectin, leptin, L/A ratio, and A-FABP levels were not statistically different between FDR and non-FDR groups. Stratified by BMI, non-obese FDR had higher L/A ratio (0.83 vs 0.49, P = 0.020) compared to those of corresponding non-FDR. In multivariate analysis, after adjusting for age, sex, waist circumference, BMI, and metabolic profiles (HbA1C, HOMA-IR, LDL-C, HDL-C, and triglyceride levels), FDR status became significantly associated with adiponectin level, and in non-obese subgroup, remained its significance with L/A ratio. ConclusionThe FDR status was independently associated with adiponectin level. Furthermore, higher L/A ratio was more pronounced in non-obese FDR than those of non-FDR subjects, suggesting that FDR status may already contribute to the development of adipokines dysregulation before obesity occurs.

Adipose Tissue and Plasma Markers Associated with HbA1c Pre- and Post-bariatric Surgery: a Cross-sectional and Cohort Study.

Obesity can be associated with chronic inflammation and dysregulated expression of inflammatory adipokines that contribute to insulin resistance and type 2 diabetes. This may also affect the clinical response to bariatric surgery. Our objective was whether baseline visceral adipose tissue features and plasma adipokine are associated with HbA1c ≥0.06 at the time of Roux-en-Y gastric bypass (RYGB) surgery and with persistently elevated HbA1c at 12 months post-RYGB. During the surgery, adipose biopsies and plasma were collected for adipokine/cytokine profile. Clinical and biochemical measurements were also collected at the time of RYGB and, in those with baseline elevated HbA1c, at 12 months post-RYGB. In the cross-sectional study, 109 patients (82.6% female; age 49 years; BMI 46.98 kg/m2) participated. Of those with elevated HbA1c at baseline (n = 61), 47 patients had repeated measurements at 12 months post-RYGB (23% drop-out). Using a multivariate logistic regression model, older age (adjusted odds ratio (aOR), 1.14; 95% confidence interval (CI), 1.06-1.22) and higher plasma resistin (aOR, 5.30; 95% CI, 1.25-22.44) were associated with higher odds of HbA1c ≥ 0.06, whereas higher plasma adiponectin (aOR, 0.993; 95% CI, 0.99-0.996) was associated with lower odds of HbA1c ≥0.06. In addition, baseline higher average adipose cell area (aOR, 1.0017; 95% CI, 1.0002-1.0032) and plasma resistin (aOR, 1.0004; 95% CI, 1.0000-1.0009) were associated with higher odds of having persistently elevated HbA1c at 12 months post-RYGB. Our study suggests that baseline plasma adipokine dysregulation, specifically high resistin, and adipocyte hypertrophy may affect the clinical response to RYGB.

Serum asprosin levels are increased and associated with insulin resistance in patients with polycystic ovary syndrome: A retrospective case-control study.

Dysregulation of adipokines may play a role in the development of polycystic ovary syndrome (PCOS). This was a retrospective case-control study to investigate the relationship between asprosin and insulin resistance in patients with PCOS patients. The study enrolled 213 PCOS patients and 213 age-matched and body mass index-matched controls. The serum asprosin levels and the relationship between asprosin and PCOS with IR were compared between the 2 groups. In the current study, it was found that the serum asprosin level and hemostasis of model assessment-insulin resistance of PCOS were significantly higher than those of the control group, and asprosin was independently correlated with hemostasis of model assessment-insulin resistance and CRP (P < .05). Asprosin was found to be statistically significant in the analysis of receiver operating characteristics, and the specific result was 0.826 (0.724-0.879). This study emphasizes that increased levels of asprosin are independently associated with PCOS, and asprosin may be a new indicator for evaluating insulin resistance in PCOS patients.

Abstract 2560: Post-translational modification of focal adhesion kinase (FAK) protein increases in breast cancer cells upon exposure to conditioned medium derived from in vitro and in vivo adipocytes

Abstract Under obese conditions, dysregulation of the normal secretion of adipokines from fat cells has been shown to drive cancer progression. However, the role adipokine dysregulation plays in driving metastasis is still unclear. Recent studies have reported the activation of metastasis-associated cell signaling pathways. One such pathway involves Focal Adhesion Kinase (FAK), a non-receptor cytoplasmic protein that acts as a signal transducer between receptor activation by adipokines and downstream effector proteins that control the biological phenomenon of metastasis. Nevertheless, the association between obesity-induced changes in adipocyte secretory factors and the subsequent increase in the transactivation of FAK through phosphorylation is unknown. To elucidate the potential relationship of adipocyte-secreted factors towards activating FAK, breast cancer cells with low (MCF7) and high (MDA-MB-231) metastatic potential were exposed to in vitro and in vivo, murine adipocyte-derived, conditioned medium. For the in vitro adipocyte model, 3T3-L1 MBX cells differentiated to obesity, with fatty acids supplementation, were used. For the in vivo model, adipocyte-secreted factors from organ-cultured visceral fat harvested from C3H/HeJ female mice fed an either high fat (46%) or control (11%) diets, were collected in the medium. Adipocyte secretions from the in vitro and in vivo adipocyte samples were determined using a mouse adipokine proteomic profiler array and ELISA kit. Under obese conditions, both the 3T3-L1 MBX cells and C3H/HeJ visceral fat were found to have significant changes in their adipokine secretions in comparison to controls. Results showed that the breast cancer cells got increased FAK autophosphorylation when exposed to either in vitro or in vivo-derived obese adipocyte-conditioned medium in comparison to the untreated breast cancer cells. Citation Format: Noshin Mubtasim, Caleb Boren, Benjamin Barr, Lauren Gollahon. Post-translational modification of focal adhesion kinase (FAK) protein increases in breast cancer cells upon exposure to conditioned medium derived from in vitro and in vivo adipocytes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2560.