Adipokine Secretion Research Articles

Targeted Inhibition of GATA-3 by Pyrrothiogatain: Implications for Adipocyte Biology and Inflammatory Response

GATA-3 is a master regulator of preadipocyte differentiation and function. Pharmacological or genetic targeting of GATA-3 will allow us to understand the function of GATA-3 in regulating metabolism, insulin signaling, and inflammation. Pyrrothiogatain, a novel small molecule inhibitor of GATA family proteins, has emerged as a promising tool for modulating GATA-3 activity. This study aims to investigate the specificity of Pyrrothiogatain in regulating GATA-3-mediated preadipocyte differentiation and adipokine secretion under normal and pathological conditions. Wild-type and GATA-3 knockout 3T3-L1 cells were treated with different concentrations of Pyrrothiogatain in the presence and absence of 4-hydroxy-2-nonenal (4HNE), an inducer of oxidative stress and impairment of adipogenesis. As expected, GATA-3 knockout cells exhibited enhanced adipogenic capacity, characterized by increased cell and lipid droplet sizes, and upregulated expression of key adipogenic markers including CEBPβ, PPARγ, and PGC-1α. Pyrrothiogatain treatment reduced cell proliferation in both wild-type and GATA-3 knockout 3T3-L1 cells, but did not alter their adipogenic capacity. Furthermore, Pyrrothiogatain lowered secreted IL-6 levels and attenuated 4-HNE-induced TNF-α elevation in wild-type, but not in GATA-3 knockout cells. Co-treatment of 4-HNE and Pyrrothiogatain led to increased cell size, suggesting complex interactions between oxidative stress and GATA protein inhibition. This effect was similar to GATA-3 knockout cells, indicating Pyrrothiogatain’s potential to modulate cellular stress responses independently of GATA-3 inhibition. These results reveal that Pyrrothiogatain’s effects on adipocyte biology extend beyond simple GATA-3 inhibition. While GATA-3 knockout primarily affects adipogenesis, Pyrrothiogatain modulates inflammatory responses and potentially cellular stress mechanisms without directly impacting adipocyte differentiation. This study provides new insights into the multifaceted actions of Pyrrothiogatain and highlights its potential as a therapeutic agent for lowering inflammation and oxidative-stress-related aspects of metabolic disorders, distinct from the direct modulation of adipogenesis.

The dual challenge of diabesity: pathophysiology, management, and future directions.

Diabesity, the concurrent occurrence of obesity and type-2 diabetes mellitus (T2DM), represents a pressing global health challenge characterized by intricate pathophysiological mechanisms and a wide range of associated comorbidities. Central to its development are insulin resistance, metabolic syndrome, and chronic low-grade inflammation mediated by dysregulated adipokine secretion and systemic metabolic dysfunction. These mechanisms underpin the progression of diabesity and its complications, including cardiovascular disease and hypertension. Management strategies encompass lifestyle interventions focusing on tailored dietary modifications and structured physical activity, pharmacological treatments targeting both glycemic control and weight loss, and surgical interventions such as bariatric surgery, which have demonstrated efficacy in achieving durable outcomes. Clinical trials and meta-analyses underscore the comparative advantages of different treatment modalities in terms of efficacy, safety, and sustainability. Moreover, long-term follow-up studies emphasize the critical need for sustained multidisciplinary interventions to prevent relapse and enhance patient outcomes. Future advancements in management include exploring precision medicine approaches that integrate individual metabolic profiles, lifestyle factors, and emerging therapeutic innovations. A multidisciplinary approach combining advanced therapeutic strategies and patient-centered care remains pivotal for optimizing management and improving prognoses for individuals with diabesity. This review highlights the complex interplay between obesity and T2DM, offering comprehensive insights into their pathophysiology, clinical presentation, and management paradigms.

PPARγ Functional Deficiency Expedited Fatty Acid Utilization in the Liver: A Foundation of Inflammatory Adipokine-Induced Hypolipemia in Rheumatoid Arthritis.

Triglyceride (TG) and its derivatives tend to be decreased in rheumatoid arthritis (RA) patients' blood when inflammation progresses. Aside from the role as a lipid buffer, white adipose tissue (WAT) contributes to this abnormality via adipokines, which regulate many metabolic signals. This work investigated adipokine-caused hepatic changes and their involvement in RA-related hypolipemia. Given their immune similarities with RA and pathological representativeness, adjuvant-induced arthritis (AIA) rats and antigen-induced arthritis (AA) mice were adopted. Adipokine levels in the liver were quantified, and their hepatic conditions were assessed by oxidative/enzymatic indicators. Besides kit-based metabolite quantification, fatty acid levels in blood were accurately determined by GC-MS. Metabolic differences between healthy and AIA rats were further characterized by UPLC-MS2. In vitro, preadipocytes were stimulated by RA/AIA blood serum or together with rosiglitazone, a PPARγ agonist. The medium was used to culture HepG2 cells. Some AIA rats were subjected to adipectomy or rosiglitazone therapies. Being WAT-released mediators, IL-1β, IL-6, MCP-1, adiponectin, and visfatin were apparently increased in AIA/AA rodent models' liver, causing oxidative stress escalation, liver injuries, and fatty acid oxidation acceleration. This metabolic change was coincided to expression increase of CD36, FABP1, ATGL, and CPT-1A. PPARγ deficiency occurred both in vivo and in vitro under rheumatic conditions. RA serum reduced PPARγ expression and impaired its inhibition on NF-κB transcription activity in preadipocytes, which then led to excessive secretion of inflammatory adipokines. The corresponding medium down-regulated PPARγ and promoted expression of lipid catabolic enzymes in HepG2 cells. These effects were abrogated by rosiglitazone. Both the therapies impeded inflammatory secretion of WAT and fat catabolism of the liver. These data demonstrate that RA potentiates the capacity of WAT to secrete inflammatory adipokines. The resulting condition represses PPARγ expression and disrupts TG anabolism/catabolism balance in the liver. Because hepatocytes utilize more lipids but synthesize less, hypolipemia develops.

A narrative review about the intricate crosstalk among endometrium, adipose tissue, and neurons in endometriosis. The multifaceted role of leptin.

Endometriosis is a highly prevalent gynecological disease characterized by the presence of endometrium-like tissue outside the uterus, whose etiopathology is far from being elucidated. The most frequent complains of patients are pelvic pain and infertility. Increasing evidence supports the systemic impact of endometriosis suggesting that an intricate crosstalk among distinct organs underlies the development of the disease. In this setting, endometriosis patients present an increased risk for developing other diseases, such as cancer, cardiovascular pathologies, and autoimmune diseases, and manifest neurologic disturbances, including neuropathic hyperalgesia. Whilst the ovary-secreted estrogen dependency of ectopic endometrium growth is well established, we conjecture that adipose tissue-secreted molecules also intervene in endometriosis development and pain manifestation. In fact, women with endometriosis present a peculiar pattern of adipokine secretion that ensues the disease onset. Unexpectedly, the levels of adipose tissue-secreted molecules in those women present similarities with those found in patients with obesity, despite the recognized association of low body mass index with endometriosis. Taking this evidence into consideration, we hypothesize that endometriosis patients present a dysfunctional adipose tissue, which is associated with enhanced metabolism and unregulated browning that not only intervene in the control of body weight but also in peculiar pain processing pathways.

Embedded Bioprinting of Breast Cancer-Adipose Composite Tissue Model for Patient-Specific Paracrine Interaction Analysis.

The interaction between breast cancer and stromal tissues varies significantly from patient to patient, greatly impacting cancer prognosis. However, conventional models struggle to accurately replicate these patient-specific interactions. Herein, a novel breast cancer-adipose composite tissue model capable of precisely adjusting the inter-tissue interaction is developed. The composite tissue model is produced through precise embedded bioprinting of breast-cancer spheroids and live-adipose-tissue ink. This model possessed not only precisely patterned cancer spheroids but also well-preserved intrinsic extracellular matrices (ECMs) and heterogeneous cell populations of adipose tissue (AT). Evaluation results successfully demonstrated that the bioprinted composite model can precisely regulate adipokine secretion, drug resistance, and cancer-cell invasion characteristics by adjusting the distance between the cancer spheroids and adipose tissue. The utility of the model is validated using adipokine-targeted therapies (C-compound/SC600125 (SC), AG 490 (AG), and Metformin (MET)). Interestingly, the inhibition of cancer cell proliferation and invasion by these adipokine-targeted drugs nearly doubled as the tissue distance decreased. This suggests that the efficacy of the drugs can be precisely evaluated using the new model. These findings underscore the potential of the developed composite model to replicate patient-specific crosstalk, thereby offering a promising platform for the sophisticated evaluation of various breast-cancer therapies.

Menopausal age, adipokines, and heart failure incidence in postmenopausal women of the Multi-Ethnic Study of Atherosclerosis.

The mechanisms through which menopausal age influences heart failure (HF) development are controversial. Adiposity increases after menopause and could affect HF risk by influencing serum adipokine secretion. We investigated the associations of early menopause, and serum adipokines with incident HF in postmenopausal women. We included 746 postmenopausal women from the Multi-Ethnic Study of Atherosclerosis who reported their menopausal age and had data on adipokines and incident HF at the end of follow-up. Multivariable Cox proportional hazards models were used for analysis. The mean age was 65.1 years. Over a median follow-up period of 17.8 years, 45 HF events occurred. After adjusting for waist circumference, other cardiovascular disease risk factors and myocardial infarction, the hazard ratios (95% confidence intervals) of incident HF attributable to early menopause were 4.50 (1.41-14.3), 4.64 (1.46-14.7), and 5.16 (1.59-16.7) in models that additionally included adiponectin, leptin, and resistin, respectively. In adjusted analyses, adiponectin was independently associated with incident HF 2.20 (1.35-3.57), while leptin and resistin were not. The interaction terms of early menopause with adiponectin, leptin, and resistin for incident HF were not significant ( Pint = 0.08-0.82). Early menopause was significantly associated with incident HF. This association did not differ by serum adipokine levels. Only adiponectin was independently associated with incident HF in postmenopausal women when waist circumference, body mass index, and waist-hip ratio were used as the adiposity metric.

Deciphering endocrine function of adipose tissue and its significant influences in obesity-related diseases caused by its dysfunction.

Current research has found that adipose tissue is not only involved in energy metabolism, but also a highly active endocrine organ that secretes various adipokines, including adiponectin, leptin, resistin and apelin, which are involved in the regulation of physiology and pathology of tissues and organs throughout the body. With the yearly increasing incidence, obesity has become a risk factor for a variety of pathological changes, including inflammation and metabolic syndrome in various system (endocrine, circulatory, locomotor and central nervous system). Thus these symptoms lead to multi-organ dysfunctions, including the heart, liver, kidneys, brain and joints. An in-depth summary of the roles of adipokines in the regulation of other tissues and organs can help to provide more effective therapeutic strategies for obesity-related diseases and explore potential therapeutic targets. Therefore, this review has retrospected the endocrine function of adipose tissue under obesity and the role of dysregulated adipokine secretion in related diseases and the underlying mechanisms, in order to provide a theoretical basis for targeting adipokine-mediated systemic dysregulation.

Brown and beige adipose tissue-derived metabokine and lipokine inter-organ signalling in health and disease.

Adipose tissue has an established endocrine function through the secretion of adipokines. However, a role for bioactive metabolites and lipids, termed metabokines and lipokines, is emerging in adipose tissue-mediated autocrine, paracrine and endocrine signalling and inter-organ communication. Traditionally seen as passive entities, metabolites are now recognized for their active roles in regulating cellular signalling and local and systemic metabolism. Distinct from white adipose tissue, specific endocrine functions have been attributed to thermogenic brown and beige adipose tissues. Brown and beige adipose tissues have been identified as sources of metabokines and lipokines, which influence diverse metabolic pathways, such as fatty acid β-oxidation, mitochondrial function and glucose homeostasis, across a range of tissues, including skeletal muscle, adipose tissue and heart. This review explores the intricate signalling mechanisms of brown and beige adipose tissue-derived metabokines and lipokines, emphasizing their roles in maintaining metabolic homeostasis and their potential dysregulation in metabolic diseases. Furthermore, we discuss the therapeutic potential of targeting these pathways, proposing that precise modulation of metabokine receptors and transporters could offer superior specificity and efficacy in comparison to conventional approaches, such as β-adrenergic signalling-stimulated activation of brown adipose tissue thermogenesis. Understanding the complex interactions between adipokines, metabokines and lipokines is essential for developing a systems-level approach to new interventions for metabolic disorders, underscoring the need for continued research in this rapidly evolving field.

The Role of Sarcopenic Obesity in Hyperlipidemia and Its Impact on Metabolic Health

Sarcopenic obesity, a condition characterized by the simultaneous presence of reduced muscle mass and increased adiposity, has emerged as a critical health concern in the context of metabolic disorders. This review examines the complex interplay between sarcopenic obesity and hyperlipidemia, focusing on the implications for metabolic health. The coexistence of diminished muscle mass and excess fat alters lipid metabolism, leading to elevated circulating lipid levels and exacerbating cardiovascular risks. Mechanisms contributing to this dysregulation include insulin resistance, chronic low-grade inflammation, and altered adipokine secretion, all of which are exacerbated in sarcopenic obesity. Moreover, the condition predisposes individuals to metabolic syndrome, type 2 diabetes, and cardiovascular diseases, highlighting the need for targeted therapeutic strategies. This article discusses the underlying pathophysiology, the role of lifestyle factors, and potential interventions aimed at mitigating the impact of sarcopenic obesity on hyperlipidemia and overall metabolic health. Keywords: Sarcopenic obesity, hyperlipidemia, metabolic health, insulin resistance, inflammation, adipokines, cardiovascular disease, metabolic syndrome

Somatic Changes of Maternal High-Fat Diet on Offspring-Possible Deleterious Effects of Flavonoids?

Background/Objectives: The rapidly increasing rate of obesity has become an extremely important public health problem, particularly in developed countries. Obesity is associated with a range of health problems, often referred to as the metabolic syndrome. Adipose tissue is now regarded as an endocrine organ responsible for the hormonal secretion of adipokines, which are cytokines involved in various physiological processes. It has been established that adipokines play a key role in the regulation of many processes in the human body. The aim of the current study was to use an animal model to investigate the possible influence of obesity and adipokines on the gestational period, on the development of offspring, and to assess whether these changes are influenced by the administration of antioxidant agents and flavonoids. Methods: The present study was performed using 5 groups of 7 female Wistar albino rats. A control group was used to which a 5% lipid diet was administered, and the other 4 groups were fed an obesogenic 65% lipid diet. From the 4 groups that received obesogenic diet one group received no supplement, and the rest of 3 received Detralex, Sel-E-Vit and Rutin (antioxidants and flavonoids). Study times for both pregnant groups and offsprings: on day 15 of gestation, venous blood was drawn to determine adipokine (leptin and visfatin) levels; on days 18-22 ultrasound examination was performed to measure the thickness of adipose tissue in the abdominal wall; for each batch a number of 10 offspring were selected for the measurements (pup weight, brain weight, head length, head width, spine length, width between shoulder blades, coxal bone length), adipokine levels in the offspring (from brain tissue) were also determined, as well as the existence of changes in the brain tissue of the offspring identified by electron microscopy. Results: The results of the study showed that the high-fat diet (HFD) led to a significant increase in body weight and abdominal wall thickness in pregnant females compared to the control group. The levels of leptin and visfatin were also affected by the HFD, with leptin levels being significantly higher in the HFD group and visfatin levels being lower. In the offspring, the HFD group had a significantly higher body mass and brain weight compared to the control group. The anthropometric measurements of the offspring were also affected by the maternal diet, with the HFD group having larger dimensions overall. Interestingly, the offspring of the groups that received flavonoids in addition to the HFD had significantly smaller dimensions compared to both the HFD group and the control group. Conclusions: The results of this experimental study reinforce what is already known about the effects of obesity on the gestation period and offspring and at the same time, the current study highlights the existence of possible adverse effects of flavonoid compounds on the development of pregnancy and offspring, opening the way for future studies on the benefits and risks of using these compounds during gestational period.

The effects of WWP1 overexpression on the golgi apparatus stress response and proteoglycan production in adipocytes

White adipocytes are a major component of white adipose tissue (WAT) and help to maintain systemic metabolic homeostasis by storing energy and secreting adipokines. In mice deficient in the protein WWP1 (WW domain-containing E3 ubiquitin protein ligase 1), oxidative stress in adipocytes increases but insulin resistance induced by obesity improves. However, the specific roles of WWP1 in adipocytes remain unclear. Here, we show that in 3T3L1 adipocytes, WWP1 localized in the Golgi apparatus via its C2 domain, where it protected the Golgi apparatus from monensin-induced disruption. By contrast, WWP1 knockdown by short hairpin RNA failed to protect the Golgi apparatus and enhanced Golgi apparatus disruption by monensin. The Golgi apparatus acts as a central organelle to establish accurate protein glycosylation of proteoglycans containing glycosaminoglycans, including chondroitin sulfate and heparan sulfate (HS). WWP1 overexpression increased chondroitin sulfate and HS levels, whereas WWP1 knockdown decreased them. Furthermore, obesity-related increases in HS were prevented by WWP1 knockout in adipose tissue. In summary, our results demonstrate a novel role for WWP1 in maintaining Golgi apparatus morphology and proteoglycan synthesis in adipocytes.

Resistin concentrations in perivascular adipose tissue as a highly sensitive marker of smoking status in patients with advanced coronary artery disease requiring coronary artery bypass grafting.

Smoking is a significant risk factor for numerous diseases, including coronary artery disease (CAD). Chronic inflammation from smoking affects endothelial function and may alter adipokine secretion, particularly resistin, in perivascular adipose tissue (PVAT). This study investigated the association between resistin concentrations in PVAT and smoking status in CAD patients undergoing coronary artery bypass grafting (CABG). The study included 110 patients with advanced CAD scheduled for CABG. Patients were categorized into never-smokers and ever-smokers, with the latter further divided into current and past smokers. Resistin concentrations in PVAT and plasma, along with plasma interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) concentrations, were measured using ELISA. Significant differences in PVAT resistin concentrations were observed between never-smokers and ever-smokers (p < 0.0001), as well as between never-smokers and both current (p < 0.0001) and past smokers (p < 0.0001). PVAT resistin concentrations correlated positively with the number of pack-years (p < 0.0001) and plasma resistin (p < 0.0001) and IL-6 concentrations (p < 0.0001). Plasma resistin, IL-6, and hs-CRP concentrations were higher in ever-smokers compared with never-smokers. Multiple regression analysis indicated that smoking is significantly correlated with higher PVAT resistin concentrations, with increased pack-years (p = 0.0002), higher plasma resistin concentrations (p < 0.0001), and IL-6 concentrations (p < 0.0001), all contributing to elevated PVAT resistin. Smoking status in advanced CAD patients requiring CABG is positively associated with PVAT resistin concentrations, with a clear demonstration of dose-dependency.

Abstract B047: Understanding the role of cancer-associated adipocytes in breast tumor microenvironment to delineate the relationship between obesity and cancer

Abstract Obesity has emerged as a prominent risk factor for the development of malignant tumors. However, the existing literature on the role of adipocytes in the tumor microenvironment (TME) to elucidate the correlation between obesity and cancer remains insufficient. Here, we aim to investigate the formation of cancer-associated adipocytes (CAAs) and their contribution to tumor growth using mouse models harboring dysfunctional adipocytes. Our results reveal that the activation of YAP/TAZ signaling in CAAs induces adipocyte dedifferentiation and the formation of a malignant TME. The additional deletion of YAP/TAZ significantly led to tumor regression by mitigating adipokine secretion such as Lipocalin2 and TNFα. Furthermore, mice fed a high- fat diet exhibit increased YAP/TAZ expression in their adipose tissues. Treatment with the YAP/TAZ inhibitor, verteporfin, suppressed tumor progression, highlighting its efficacy against mice with metabolic dysregulation. These findings provide insights into the key mediators of CAA transformation and their significance in developing a TME. Our study extends to the impact of maladaptive adipocytes as a TME component. We gather multi-omics results including single-nucleus RNA sequencing and spatial transcriptomics (Xenium) to identify the CAA population in the peritumoral region. CAAs are found to modulate the TME via interacting with multiple immune cells, especially macrophages. Xenium result visualizes the proximity between CAAs and macrophages, indicating their cellular interaction. Additionally, our in-vitro co- culture system shows that CAAs recruit macrophages more effectively compared to normal adipocytes. Overall, we strive to understand the importance of adipocyte quality in forming a malignant TME and ultimately introduce therapeutic strategies targeting the tumor microenvironment, especially adipocytes. Citation Format: Yaechan Song, Hee Ju Na, Han Woong Lee. Understanding the role of cancer-associated adipocytes in breast tumor microenvironment to delineate the relationship between obesity and cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B047.

Effect of Comparable Carbon Chain Length Short- and Branched-Chain Fatty Acids on Adipokine Secretion from Normoxic and Hypoxic Lipopolysaccharide-Stimulated 3T3-L1 Adipocytes.

Background: Microbial fermentation of non-digestible carbohydrates and/or protein produces short-chain fatty acids (SCFA), whereas branched-chain fatty acids (BCFA) are produced from protein fermentation. The effects of individual SCFA and BCFA of comparable carbon chain length on adipocyte inflammation have not been investigated. Objective: To compare the effects of SCFA and BCFA on inflammatory mediator secretion in an adipocyte cell culture model designed to recapitulate obesity-associated adipocyte inflammation under normoxic and hypoxic conditions. Methods: The 3T3-L1 adipocytes were cultured (24 h) without (Control, Con) and with 1 mmol/L of SCFA (butyric acid (But) or valeric acid (Val)) or 1 mmol/L of BCFA (isobutyric acid (IsoBut) or isovaleric acid (IsoVal)) and were unstimulated (cells alone, n = 6/treatment), or stimulated with 10 ng/mL lipopolysaccharide (LPS, inflammatory stimulus, n = 8/treatment) or 10 ng/mL LPS + 100 µmol/L of the hypoxia memetic cobalt chloride (LPS/CC, inflammatory/hypoxic stimulus, n = 8/treatment). Results: Compared to Con + LPS, But + LPS reduced secreted protein levels of interleukin (IL)-1β, IL-6, macrophage chemoattractant protein (MCP)-1/chemokine ligand (CCL)2, MCP3/CCL7, macrophage inflammatory protein (MIP)-1α/CCL3 and regulated upon activation, normal T cell expressed, and secreted (RANTES)/CCL5 and decreased intracellular protein expression of the ratio of phosphorylated to total signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa B (NFκB) p65 (p < 0.05). Val + LPS reduced IL-6 secretion and increased MCP-1/CCL2 secretion compared to Con + LPS and exhibited a different inflammatory mediator secretory profile from But + LPS (p < 0.05), indicating that individual SCFA exert individual effects. There were no differences in the secretory profile of the BCFA IsoBut + LPS and IsoVal + LPS (p > 0.05). Alternatively, under inflammatory hypoxic conditions (LPS/CC) Val, IsoVal, and IsoBut all increased secretion of IL-6, MCP-1/CCL2 and MIP-1α/CCL3 compared to Con (p < 0.05), whereas mediator secretion did not differ between But and Con (p > 0.05), indicating that the proinflammatory effects of SCFA and BCFA was attenuated by But. Interestingly, But + LPS/CC decreased STAT3 activation versus Con + LPS/CC (p < 0.05). Conclusions: The decreased secretion of inflammatory mediators that is attributable to But highlights the fact that individual SCFA and BCFA exert differential effects on adipocyte inflammation under normoxic and hypoxic conditions.

Adipose Tissues Have Been Overlooked as Players in Prostate Cancer Progression.

Obesity is a common risk factor in multiple tumor types, including prostate cancer. Obesity has been associated with driving metastasis, therapeutic resistance, and increased mortality. The effect of adipose tissue on the tumor microenvironment is still poorly understood. This review aims to highlight the work conducted in the field of obesity and prostate cancer and bring attention to areas where more research is needed. In this review, we have described key differences between healthy adipose tissues and obese adipose tissues, as they relate to the tumor microenvironment, focusing on mechanisms related to metabolic changes, abnormal adipokine secretion, altered immune cell presence, and heightened oxidative stress as drivers of prostate cancer formation and progression. Interestingly, common treatment options for prostate cancer ignore the adipose tissue located near the site of the tumor. Because of this, we have outlined how excess adipose tissue potentially affects therapeutics' efficacy, such as androgen deprivation, chemotherapy, and radiation treatment, and identified possible drug targets to increase prostate cancer responsiveness to clinical treatments. Understanding how obesity affects the tumor microenvironment will pave the way for understanding why some prostate cancers become metastatic or treatment-resistant, and why patients experience recurrence.

Influence of melatonin on the development of obesity

In recent years, increasing attention of researchers has been paid to the role of melatonin in the regulation of body weight. When analyzing literature data, the problem of the mechanism of action of melatonin on the body and its use in the correction of metabolic disorders is considered. Disruption of circadian rhythms caused by the use of artificial light at night leads to decreased melatonin secretion. This helps increase appetite and reduce energy costs. In addition, melatonin plays a major role in modulating the secretion of adipokines by influencing lipid metabolism. Decreased melatonin production causes insulin resistance and metabolic circadian disorganization, leading to obesity. Assessing the role of melatonin in the development of obesity and its accompanying pathologies is a promising area of scientific research in the field of diagnosis, prevention and treatment of endocrine and cardiovascular pathologies.

Human peripancreatic adipose tissue paracrine signaling impacts insulin secretion, blood flow, and gene transcription.

Adipose tissue accumulation around non-adipose tissues is associated with obesity and metabolic disease. One relatively unstudied depot is peripancreatic adipose tissue (PAT) that accumulates in obesity and insulin resistance and may impact beta cell function. Pancreatic lipid accumulation and PAT content are negatively related to metabolic outcomes in humans, but these studies are limited by the inability to pursue mechanisms. We obtained PAT from human donors through the Human Pancreas Analysis Program to evaluate differences in paracrine signaling compared to subcutaneous adipose tissue (SAT), as well as effects of the PAT secretome on aortic vasodilation, human islet insulin secretion, and gene transcription using RNAseq. PAT had greater secretion of IFN-γ and most inflammatory eicosanoids compared to SAT. Secretion of adipokines negatively related to metabolic health were also increased in PAT compared to SAT. We found no overall effects of PAT compared to SAT on human islet insulin secretion, however, insulin secretion was suppressed after PAT exposure from men compared to women. Vasodilation was significantly dampened by PAT conditioned media, an effect explained almost completely by PAT from men and not women. Islets treated with PAT showed selective changes in lipid metabolism pathways while SAT altered cellular signaling and growth. RNAseq analysis showed changes in islet gene transcription impacted by PAT compared to SAT, with the biggest changes found between PAT based on sex. The PAT secretome is metabolically negative compared to SAT, and impacts islet insulin secretion, blood flow, and gene transcription in a sex dependent manner.

Diverse Cytokines Secreted by Adipocyte in Linking Cardio-Metabolic Disorder and SLE.

Systemic lupus erythematosus (SLE) is a multi-factorial autoimmune-mediated disease with hyper-stimulation of immune cells especially the T lymphocytes. By this method, it might facilitate the systematic damages in multiple tissues and organs. Otherwise, SLE is also correlated with diverse cardio-metabolic comorbidities, including dyslipidemia, insulin resistance, and hypertension. It is worth-noting that the risk of cardio-metabolic disorders is significantly higher compared with the healthy patients which was reported as approximately one-third of SLE patients were proved as obesity. Notably, current focus is shifting to implementing cardio-metabolic protective strategies as well as elucidating underlying mechanisms of lupus-mediated obese status. On the other hand, adipocyte, as the most abundant endocrine cell in fat tissue, are dysfunctional in obese individuals with aberrant secretion of adipokines. It is proposing that the adipokine might link the pathology of cardio-metabolic disorders and SLE, whereas the related mechanism is complicated. In the current review, the functions of adipokine and the potential mechanisms by which the adipokine link cardio-metabolic disorders and SLE was well listed. Furthermore, the recommendations, which identify the adipokine as the potential therapeutic targets for the treatment of cardio-metabolic disorders and SLE, were also summarized.

The Complement System as a Part of Immunometabolic Post-Exercise Response in Adipose and Muscle Tissue.

The precise molecular processes underlying the complement's activation, which follows exposure to physical stress still remain to be fully elucidated. However, some possible mechanisms could play a role in initiating changes in the complement's activity, which are observed post-exposure to physical stress stimuli. These are mainly based on metabolic shifts that occur in the microenvironment of muscle tissue while performing its function with increased intensity, as well as the adipose tissue's role in sterile inflammation and adipokine secretion. This review aims to discuss the current opinions on the possible link between the complement activation and diet, age, sex, and health disorders with a particular emphasis on endocrinopathies and, furthermore, the type of physical activity and overall physical fitness. It has been indicated that regular physical activity incorporated into therapeutic strategies potentially improves the management of particular diseases, such as, e.g., autoimmune conditions. Moreover, it represents a favorable influence on immunoaging processes. A better understanding of the complement system's interaction with physical activity will support established clinical therapies targeting complement components.

Body mass index as a contributor to the accumulation of lipidic plaque materials in statin-treated type 2 diabetic patients with coronary artery disease: sub-analysis from the OPTIMAL randomized study

Abstract Background Patients with type 2 diabetes mellitus more likely exhibit obesity. Pathophysiologically, obesity promotes a range of metabolic disturbances including insulin resistance, dyslipidemia and hypertension, in addition to the secretion of adipokines and pro-inflammatory cytokines from excessive fat accumulation. These atherogenic features may promote instability of atherosclerotic plaques, which ultimately result in elevating a risk of atherosclerotic cardiovascular disease. However, it remains to be fully elucidated how obesity affects atherosclerotic plaque features in type 2 diabetic patients with coronary artery disease (CAD). Near-infrared spectroscopy (NIRS) imaging enables to quantitatively visualize lipidic plaque materials in vivo. This imaging modality provides insights into lipidic plaque features in obese patients with type 2 diabetes mellitus. Purpose To elucidate the association of body mass index (BMI, kg/m2) with lipidic plaque materials in type 2 diabetic patients. Methods The OPTIMAL study was a prospective randomized controlled trial to evaluate the efficacy of continuous glucose monitoring (CGM) guided glycemic control on coronary atherosclerosis in statin-treated type 2 diabetic participants with CAD requiring PCI. 94 patients were randomized into CGM-guided or HbA1c-guided glycemic control. Serial NIRS imaging was conducted to monitor non-culprit lesions at baseline and week 48. The current sub-analysis included 78 patients with both baseline BMI data and evaluable baseline NIRS/IVUS images. Results All of study subjects received a statin (high-intensity statin use=36%), and the averaged LDL-C level was 86.7±26.3 mg/dL. The average BMI and HbA1c level were 24.7±3.1 kg/m2 and 7.5±0.9%, respectively (Table 1). On NIRS imaging analysis, maxLCBI4mm at non-culprit lesions was 286.2±167.0, and 21.8% of study subjects exhibited maxLCBI4mm &amp;gt;400 (Table 2). BMI was associated with maxLCBI4mm (p&amp;lt;0.001). Multivariate analysis adjusting clinical characteristics and LDL-C demonstrated that BMI was an independent contributor to maxLCBI4mm [estimate=17.15 (12.88-21.42), p&amp;lt;0.001] (Table 2). Even in patients receiving high-intensity statin, BMI was still associated with maxLCBI4mm (p&amp;lt;0.001). Conclusions A greater accumulation of lipidic plaque materials was observed in association with BMI in statin-treated type 2 diabetic patients with CAD. This presence of enhanced plaque vulnerability at non-culprit lesions, in the setting of obesity, may contribute to an increased risk of cardiovascular events in type 2 diabetic patients with CAD. The current finding suggests the need to adopt further therapeutic approaches to favourably modify plaque vulnerability in type 2 diabetic patients exhibiting obesity.Table 1:Clinical DemographicsTable 2:Factors Associated with maxLCBI