Targeting GSK-3β for adipose dysfunction and cardiovascular complications of metabolic disease: An entangled WNT/β-catenin question.

Individuals with metabolic syndrome have a high risk of developing cardiovascular disorders that is closely tied to visceral adipose tissue dysfunction, as well as an altered interaction between adipose tissue and the cardiovascular system. In metabolic syndrome, adipose tissue dysfunction is associated with increased hypertrophy, reduced vascularization, and hypoxia of adipocytes, leading to a pro-oxidative and pro-inflammatory environment. Among the pathways regulating adipose tissue homeostasis is the wingless-type mammary tumor virus integration site family (Wnt) signaling pathway, with both its canonical and non-canonical arms.

Interruption of perivascular and perirenal adipose tissue thromboinflammation rescues prediabetic cardioautonomic and renovascular deterioration.

The cardiovascular and renovascular complications of metabolic deterioration are associated with localized adipose tissue dysfunction. We have previously demonstrated that metabolic impairment delineated the heightened vulnerability of both the perivascular (PVAT) and perirenal adipose tissue (PRAT) depots to hypoxia and inflammation, predisposing to cardioautonomic, vascular and renal deterioration. Interventions either addressing underlying metabolic disturbances or halting adipose tissue dysfunction rescued the observed pathological and functional manifestations.

Periprostatic adipose tissue thromboinflammation triggers prostatic neoplasia in early metabolic impairment: Interruption by rivaroxaban.

Aims: Prostate cancer is among the highest incidence malignancies in men with a prevalence rate increasing in parallel to the rising global trends in metabolic disorders. Whereas a sizeable body of evidence links metabolic impairment to negative prognosis of prostate cancer, the molecular mechanism underlying this connection has not been thoroughly examined. Our previous work showed that localized adipose tissue inflammation occurring in select adipose depots in early metabolic derangement instigated significant molecular, structural, and functional alterations in neighboring tissues underlying the complications observed at this stage.

The evolving functions of the vasculature in regulating adipose tissue biology in health and obesity.

Adipose tissue is an endocrine organ and a crucial regulator of energy storage and systemic metabolic homeostasis. Additionally, adipose tissue is a pivotal regulator of cardiovascular health and disease, mediated in part by the endocrine and paracrine secretion of several bioactive products, such as adipokines. Adipose vasculature has an instrumental role in the modulation of adipose tissue expansion, homeostasis and metabolism.

Adipose tissue endothelial cells: insights into their heterogeneity and functional diversity.

Cardiovascular disease is the leading cause of death globally. Endothelial cells (ECs), the key units of all vascular segments, have a significant impact on the health and disease of organisms. Adipose tissue is vital to cardiovascular health, therefore, understanding adipose EC (AdEC) biology is important.

Depot-specific adipose tissue modulation by SGLT2 inhibitors and GLP1 agonists mediates their cardioprotective effects in metabolic disease.

Sodium-glucose transporter-2 inhibitors (SGLT-2i) and glucagon-like peptide 1 (GLP-1) receptor agonists are newer antidiabetic drug classes, which were recently shown to decrease cardiovascular (CV) morbidity and mortality in diabetic patients. CV benefits of these drugs could not be directly attributed to their blood glucose lowering capacity possibly implicating a pleotropic effect as a mediator of their impact on cardiovascular disease (CVD). Particularly, preclinical and clinical studies indicate that SGLT-2i(s) and GLP-1 receptor agonists are capable of differentially modulating distinct adipose pools reducing the accumulation of fat in some depots, promoting the healthy expansion of others, and/or enhancing their browning, leading to the suppression of the metabolically induced inflammatory processes.

Adipose tissue mitochondrial dysfunction and cardiometabolic diseases: On the search for novel molecular targets.

Cardiometabolic diseases present an escalating global health and economic burden. Such a surge is driven by epidemic prevalence rates of metabolic disorders, such as obesity and type 2 diabetes, and their associated cardiovascular complications, majorly contributing to morbidity and mortality. A fundamental challenge impeding the effective management and therapy of these complications is a lack of clear understanding of the molecular mechanisms underpinning disease initiation and progression.

Metformin, pioglitazone, dapagliflozin and their combinations ameliorate manifestations associated with NAFLD in rats via anti-inflammatory, anti-fibrotic, anti-oxidant and anti-apoptotic mechanisms.

Non-alcoholic fatty liver disease (NAFLD) is an important health threat that is strongly linked to components of metabolic syndrome, particularly the low-grade inflammatory changes. Significantly, several of the available anti-diabetic drug classes demonstrate a considerable anti-inflammatory effect, and hence might be of benefit for NAFLD patients. In this study, we used a rat model of diet-induced NAFLD to examine the potential effect of metformin, pioglitazone, dapagliflozin and their combinations on NAFLD manifestations.

Pathophysiology of Coagulation and Emerging Roles for Extracellular Vesicles in Coagulation Cascades and Disorders.

The notion of blood coagulation dates back to the ancient Greek civilization. However, the emergence of innovative scientific discoveries that started in the seventeenth century formulated the fundamentals of blood coagulation. Our understanding of key coagulation processes continues to evolve, as novel homeostatic and pathophysiological aspects of hemostasis are revealed.

Early metabolic impairment as a contributor to neurodegenerative disease: Mechanisms and potential pharmacological intervention.

The metabolic syndrome comprises a family of clinical and laboratory findings, including insulin resistance, hyperglycemia, hypertriglyceridemia, low high-density lipoprotein cholesterol levels, and hypertension, in addition to central obesity. The syndrome confers a high risk of cardiovascular mortality. Indeed, metabolic dysfunction has been shown to cause a direct insult to smooth muscle and endothelial components of the vasculature, which leads to vascular dysfunction and hyperreactivity.

Thromboinflammatory Processes at the Nexus of Metabolic Dysfunction and Prostate Cancer: The Emerging Role of Periprostatic Adipose Tissue.

The increased global prevalence of metabolic disorders including obesity, insulin resistance, metabolic syndrome and diabetes is mirrored by an increased incidence of prostate cancer (PCa). Ample evidence suggests that these metabolic disorders, being characterized by adipose tissue (AT) expansion and inflammation, not only present as risk factors for the development of PCa, but also drive its increased aggressiveness, enhanced progression, and metastasis. Despite the emerging molecular mechanisms linking AT dysfunction to the various hallmarks of PCa, thromboinflammatory processes implicated in the crosstalk between these diseases have not been thoroughly investigated.

Phosphorus Supplementation Mitigates Perivascular Adipose Inflammation-Induced Cardiovascular Consequences in Early Metabolic Impairment.

Background The complexity of the interaction between metabolic dysfunction and cardiovascular complications has long been recognized to extend beyond simple perturbations of blood glucose levels. Yet, structured interventions targeting the root pathologies are not forthcoming. Growing evidence implicates the inflammatory changes occurring in perivascular adipose tissue (PVAT) as early instigators of cardiovascular deterioration.

Sex Differences in Cardiovascular Impact of Early Metabolic Impairment: Interplay between Dysbiosis and Adipose Inflammation.

The evolving view of gut microbiota has shifted toward describing the colonic flora as a dynamic organ in continuous interaction with systemic physiologic processes. Alterations of the normal gut bacterial profile, known as dysbiosis, has been linked to a wide array of pathologies. Of particular interest is the cardiovascular-metabolic disease continuum originating from positive energy intake and high-fat diets.

Knowledge and Beliefs of Cancer Risk Factors and Early Cancer Symptoms in Lebanon: A Cross-sectional Survey Among Adults in the Community.

Background: Lebanon has an increasing cancer burden. Sufficient knowledge of cancer risk factors and early cancer symptoms can help lower cancer burden by facilitating primary prevention and early diagnosis. This study (i) assessed Lebanese adults' knowledge and beliefs of cancer risk factors and early cancer symptoms, (ii) analyzed whether knowledge was correlated with personal behavior, and (iii) assessed the presence of barriers that keep knowledge from turning into healthcare seeking behavior.

Perirenal Adipose Tissue Inflammation: Novel Insights Linking Metabolic Dysfunction to Renal Diseases.

A healthy adipose tissue (AT) is indispensable to human wellbeing. Among other roles, it contributes to energy homeostasis and provides insulation for internal organs. Adipocytes were previously thought to be a passive store of excess calories, however this view evolved to include an endocrine role.

Transforming iodoquinol into broad spectrum anti-tumor leads: Repurposing to modulate redox homeostasis.

We managed to repurpose the old drug iodoquinol to a series of novel anticancer 7-iodo-quinoline-5,8-diones. Twelve compounds were identified as inhibitors of moderate to high potency on an inhouse MCF-7 cell line, of which 2 compounds (5 and 6) were capable of reducing NAD level in MCF-7 cells in concentrations equivalent to half of their ICs, potentially due to NAD(P)H quinone oxidoreductase (NQO1) inhibition. The same 2 compounds (5 and 6) were capable of reducing p53 expression and increasing reactive oxygen species levels, which further supports the NQO-1 inhibitory activity.

Modulatory Effect of Intermittent Fasting on Adipose Tissue Inflammation: Amelioration of Cardiovascular Dysfunction in Early Metabolic Impairment.

Cardiometabolic syndrome (CMS) is a cluster of maladaptive cardiovascular, renal, thrombotic, inflammatory, and metabolic disorders. It confers a high risk of cardiovascular mortality and morbidity. CMS is triggered by major shifts in lifestyle and dietary habits with increased consumption of refined, calorie-dense diets.

The pleiotropic effects of antithrombotic drugs in the metabolic-cardiovascular-neurodegenerative disease continuum: impact beyond reduced clotting.

Antithrombotic drugs are widely used for primary and secondary prevention, as well as treatment of many cardiovascular disorders. Over the past few decades, major advances in the pharmacology of these agents have been made with the introduction of new drug classes as novel therapeutic options. Accumulating evidence indicates that the beneficial outcomes of some of these antithrombotic agents are not solely related to their ability to reduce thrombosis.

Peri-renal adipose inflammation contributes to renal dysfunction in a non-obese prediabetic rat model: Role of anti-diabetic drugs.

Diabetic nephropathy is a major health challenge with considerable economic burden and significant impact on patients' quality of life. Despite recent advances in diabetic patient care, current clinical practice guidelines fall short of halting the progression of diabetic nephropathy to end-stage renal disease. Moreover, prior literature reported manifestations of renal dysfunction in early stages of metabolic impairment prior to the development of hyperglycemia indicating the involvement of alternative pathological mechanisms apart from those typically triggered by high blood glucose.

Adipose Tissue Immunomodulation: A Novel Therapeutic Approach in Cardiovascular and Metabolic Diseases.

Adipose tissue is a critical regulator of systemic metabolism and bodily homeostasis as it secretes a myriad of adipokines, including inflammatory and anti-inflammatory cytokines. As the main storage pool of lipids, subcutaneous and visceral adipose tissues undergo marked hypertrophy and hyperplasia in response to nutritional excess leading to hypoxia, adipokine dysregulation, and subsequent low-grade inflammation that is characterized by increased infiltration and activation of innate and adaptive immune cells. The specific localization, physiology, susceptibility to inflammation and the heterogeneity of the inflammatory cell population of each adipose depot are unique and thus dictate the possible complications of adipose tissue chronic inflammation.

The Emerging Role of COX-2, 15-LOX and PPARγ in Metabolic Diseases and Cancer: An Introduction to Novel Multi-target Directed Ligands (MTDLs).

Emerging evidence supports an intertwining framework for the involvement of different inflammatory pathways in a common pathological background for a number of disorders. Of importance are pathways involving arachidonic acid metabolism by cyclooxygenase-2 (COX-2) and 15-lipoxygenase (15-LOX). Both enzyme activities and their products are implicated in a range of pathophysiological processes encompassing metabolic impairment leading to adipose inflammation and the subsequent vascular and neurological disorders, in addition to various pro- and antitumorigenic effects.