scholarly journals Recent Advances in Understanding the Role of IKKβ in Cardiometabolic Diseases

2021 ◽  
Vol 8 ◽  
Author(s):  
Rebecca Hernandez ◽  
Changcheng Zhou
Keyword(s):  
Vascular Function ◽  
Current Knowledge ◽  
Central Adiposity ◽  
Mortality And Morbidity ◽  
Cardiometabolic Diseases ◽  
Highly Active ◽  
Iκb Kinase ◽  
Obesity And Diabetes ◽  
Promising Therapeutic Target

Cardiometabolic diseases, including cardiovascular disease, obesity, and diabetes, are the leading cause of mortality and morbidity worldwide. Cardiometabolic diseases are associated with many overlapping metabolic syndromes such as hypertension, hyperlipidemia, insulin resistance, and central adiposity. However, the underlying causes of cardiometabolic diseases and associated syndromes remain poorly understood. Within the past couple of decades, considerable progresses have been made to understand the role of inflammatory signaling in the pathogenesis of cardiometabolic diseases. The transcription factor, NF-κB, a master regulator of the innate and adaptive immune responses, is highly active in cardiometabolic diseases. IκB kinase β (IKKβ), the predominant catalytic subunit of the IKK complex, is required for canonical activation of NF-κB, and has been implicated as the critical molecular link between inflammation and cardiometabolic diseases. Recent studies have revealed that IKKβ has diverse and unexpected roles in mediating adiposity, insulin sensitivity, glucose homeostasis, vascular function, and atherogenesis through complex mechanisms. IKKβ has been demonstrated as a critical player in the development of cardiometabolic diseases and is implicated as a promising therapeutic target. This review summarizes current knowledge of the functions of IKKβ in mediating the development and progression of cardiometabolic diseases.

Obesity and diabetes: lipids, ‘nowhere to run to'

2008 ◽  
Vol 116 (2) ◽  
pp. 113-123 ◽  
Author(s):  
Margaret J. Hill ◽  
David Metcalfe ◽  
Philip G. McTernan
Keyword(s):  
Short Review ◽  
Therapeutic Strategies ◽  
Cellular Systems ◽  
Ectopic Fat ◽  
Central Adiposity ◽  
Disease Pathogenesis ◽  
Fat Accumulation ◽  
Obesity And Diabetes

Although specific pathogenic entities contributing to diabetic risk, such as central adiposity, ectopic fat accumulation, hyperlipidaemia and inflammation, are well-characterized, the response of cellular systems to such insults are less well understood. This short review highlights the effect of increasing fat mass on ectopic fat accumulation, the role of triacylglycerols (triglycerides) in Type 2 diabetes mellitus and cardiovascular disease pathogenesis, and selected current therapeutic strategies used to ameliorate these risk factors.

Role of angiotensin-converting enzyme 2 (ACE2) in diabetic cardiovascular complications

2013 ◽  
Vol 126 (7) ◽  
pp. 471-482 ◽  
Author(s):  
Vaibhav B. Patel ◽  
Nirmal Parajuli ◽  
Gavin Y. Oudit
Keyword(s):  
Diabetes Mellitus ◽  
Angiotensin Converting Enzyme ◽  
Vascular Function ◽  
Systolic Dysfunction ◽  
Cardiovascular Complications ◽  
Converting Enzyme ◽  
Converting Enzyme Inhibitors ◽  
Obesity And Diabetes

Diabetes mellitus results in severe cardiovascular complications, and heart disease and failure remain the major causes of death in patients with diabetes. Given the increasing global tide of obesity and diabetes, the clinical burden of diabetes-induced cardiovascular disease is reaching epidemic proportions. Therefore urgent actions are needed to stem the tide of diabetes which entails new prevention and treatment tools. Clinical and pharmacological studies have demonstrated that AngII (angiotensin II), the major effector peptide of the RAS (renin–angiotensin system), is a critical promoter of insulin resistance and diabetes mellitus. The role of RAS and AngII has been implicated in the progression of diabetic cardiovascular complications and AT1R (AngII type 1 receptor) blockers and ACE (angiotensin-converting enzyme) inhibitors have shown clinical benefits. ACE2, the recently discovered homologue of ACE, is a monocarboxypeptidase which converts AngII into Ang-(1–7) [angiotensin-(1–7)] which, by virtue of its actions on the MasR (Mas receptor), opposes the effects of AngII. In animal models of diabetes, an early increase in ACE2 expression and activity occurs, whereas ACE2 mRNA and protein levels have been found to decrease in older STZ (streptozotocin)-induced diabetic rats. Using the Akita mouse model of Type 1 diabetes, we have recently shown that loss of ACE2 disrupts the balance of the RAS in a diabetic state and leads to AngII/AT1R-dependent systolic dysfunction and impaired vascular function. In the present review, we will discuss the role of the RAS in the pathophysiology and treatment of diabetes and its complications with particular emphasis on potential benefits of the ACE2/Ang-(1–7)/MasR axis activation.

scholarly journals Modulation of Obesity and Insulin Resistance by the Redox Enzyme and Adaptor Protein p66Shc

2019 ◽  
Vol 20 (4) ◽  
pp. 985 ◽  
Author(s):  
Stefano Ciciliot ◽  
Gian Fadini
Keyword(s):  
Insulin Resistance ◽  
Reactive Oxygen Species ◽  
Metabolic Pathways ◽  
Adaptor Protein ◽  
Oxygen Species ◽  
Related Protein ◽  
Redox Enzyme ◽  
Obesity And Diabetes ◽  
Promising Therapeutic Target

Initially reported as a longevity-related protein, the 66 kDa isoform of the mammalian Shc1 locus has been implicated in several metabolic pathways, being able to act both as an adaptor protein and as a redox enzyme capable of generating reactive oxygen species (ROS) when it localizes to the mitochondrion. Ablation of p66Shc has been shown to be protective against obesity and the insurgence of insulin resistance, but not all the studies available in the literature agree on these points. This review will focus in particular on the role of p66Shc in the modulation of glucose homeostasis, obesity, body temperature, and respiration/energy expenditure. In view of the obesity and diabetes epidemic, p66Shc may represent a promising therapeutic target with enormous implications for human health.

scholarly journals Obesity, pregnancy, inflammation, and vascular function

Reproduction ◽  
2010 ◽  
Vol 140 (3) ◽  
pp. 373-385 ◽  
Author(s):  
F C Denison ◽  
K A Roberts ◽  
S M Barr ◽  
J E Norman
Keyword(s):  
Adipose Tissue ◽  
Vascular Endothelium ◽  
Vascular Function ◽  
Maternal Obesity ◽  
Current Knowledge ◽  
Adverse Pregnancy Outcome ◽  
Tissue Biology ◽  
Increased Risk ◽  
Adverse Pregnancy

Maternal obesity is associated with increased morbidity and mortality for both mother and offspring. The mechanisms underlying the increased risk associated with maternal obesity are not well understood. In non-pregnant populations, many of the complications of obesity are thought to be mediated in part by inflammation and its sequelae. Recent studies suggest that a heightened inflammatory response may also be involved in mediating adverse clinical outcomes during pregnancy. This review summarizes our current knowledge about adipose tissue biology, and its role as an endocrine and inflammatory organ. The evidence for inflammation as a key mediator of adverse pregnancy outcome is also presented, focusing on the role of inflammation in adipose tissue, systemic inflammation, the placenta, and vascular endothelium.

scholarly journals The vascular epigenome in patients with obesity and type 2 diabetes: opportunities for personalized therapies

2020 ◽  
Vol 2 (1) ◽  
pp. H19-H28 ◽  
Author(s):  
Sarah Costantino ◽  
Shafeeq A Mohammed ◽  
Samuele Ambrosini ◽  
Francesco Paneni
Keyword(s):  
Type 2 Diabetes ◽  
Vascular Function ◽  
Current Knowledge ◽  
Vascular Dysfunction ◽  
Vascular Complications ◽  
Epigenetic Modifications ◽  
Individual Risk ◽  
Limited Information ◽  
Obesity And Diabetes

Our genetic background provides limited information on individual risk of developing vascular complications overtime. New biological layers, namely epigenetic modifications, are now emerging as potent regulators of gene expression thus leading to altered transcriptional programs and vascular disease phenotypes. Such epigenetic modifications, defined as changes to the genome that do not involve changes in DNA sequence, are generally induced by environmental factors and poor lifestyle habits. Of note, adverse epigenetic signals acquired during life can be transmitted to the offspring thus leading to premature alterations of the epigenetic and transcriptional landscape eventually leading to early endothelial dysfunction and vascular senescence. Modifications of the epigenome play a pivotal role in the pathophysiology of cardiometabolic disturbances such as obesity and type 2 diabetes. In these patients, changes of DNA methylation and chromatin structure contribute to alter pathways regulating insulin sensitivity, glucose homeostasis, adipogenesis and vascular function. In this perspective, unveiling the ‘epigenetic landscape’ in cardiometabolic patients may help to identify new players implicated in obesity and diabetes-related vascular dysfunction and may pave the way for personalized therapies in this setting. In the present review, we discuss current knowledge of the epigenetic routes implicated in vascular damage and cardiovascular disease in patients with metabolic alterations.

scholarly journals From Notochord Formation to Hereditary Chordoma: The Many Roles ofBrachyury

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Yutaka Nibu ◽  
Diana S. José-Edwards ◽  
Anna Di Gregorio
Keyword(s):  
Current Knowledge ◽  
Bone Cancer ◽  
Axial Skeleton ◽  
Promising Therapeutic Target ◽  
Fourth Decade ◽  
Notochord Cells ◽  
The Many ◽  
Main Regulator ◽  
Modern Technologies

Chordoma is a rare, but often malignant, bone cancer that preferentially affects the axial skeleton and the skull base. These tumors are both sporadic and hereditary and appear to occur more frequently after the fourth decade of life; however, modern technologies have increased the detection of pediatric chordomas. Chordomas originate from remnants of the notochord, the main embryonic axial structure that precedes the backbone, and share with notochord cells both histological features and the expression of characteristic genes. One such gene isBrachyury, which encodes for a sequence-specific transcription factor. Known for decades as a main regulator of notochord formation,Brachyuryhas recently gained interest as a biomarker and causative agent of chordoma, and therefore as a promising therapeutic target. Here, we review the main characteristics of chordoma, the molecular markers, and the clinical approaches currently available for the early detection and possible treatment of this cancer. In particular, we report on the current knowledge of the role ofBrachyuryand of its possible mechanisms of action in both notochord formation and chordoma etiogenesis.

scholarly journals Nutrition and the HIV-associated lipodystrophy syndrome

2012 ◽  
Vol 25 (2) ◽  
pp. 267-287 ◽  
Author(s):  
Cathríona Rosemary Loonam ◽  
Anne Mullen
Keyword(s):  
Highly Active Antiretroviral Therapy ◽  
Current Knowledge ◽  
Pufa Supplementation ◽  
Morphological Alterations ◽  
Lipodystrophy Syndrome ◽  
Beneficial Effects ◽  
Highly Active ◽  
Increased Risk ◽  
Randomised Controlled

HIV-associated lipodystrophy syndrome (HALS), comprising metabolic and morphological alterations, is a known side effect of highly active antiretroviral therapy (HAART). Evidence for the role of nutrition in the management of the systemic parameters of HALS is currently limited. In the present paper we review the current knowledge base surrounding HALS, focusing particularly on the role of nutrition in mitigating the systemic parameters of the syndrome. Reported prevalence of HALS was found to vary from 9 to 83 % due to lack of a standardised definition, as well as variations in assessment methods and in the study population used. HALS is associated with both morphological (lipoatrophy, lipohypertrophy) and metabolic (dyslipidaemia, glucose intolerance, diabetes, hypertension, endothelial dysfunction and atherosclerosis) alterations, which may occur singly or in combination, and are associated with an increased risk of CVD. HAART-induced adipocyte inflammation, oxidative stress and macrophage infiltration, as well as altered adipocyte function and mitochondrial toxicity, have been shown to be central to the development of HALS. The adipocyte, therefore, represents a plausible target for treatment. Pharmacological and surgical treatment interventions have shown effect. However, their use is associated with numerous adverse effects and complications. Targeted lifestyle interventions may provide a useful alternative for managing HALS owing to their safety and tolerability. A Mediterranean-style diet has been found to be effective in improving the systemic parameters of HALS. Furthermore, the effects of n-3 PUFA supplementation are encouraging and future randomised controlled trials investigating the beneficial effects of n-3 PUFA in HALS are justified.

scholarly journals The role of orexin in controlling the activity of the adipo-pancreatic axis

2018 ◽  
Vol 238 (2) ◽  
pp. R95-R108 ◽  
Author(s):  
M Skrzypski ◽  
M Billert ◽  
K W Nowak ◽  
M Z Strowski
Keyword(s):  
Energy Homeostasis ◽  
Current Knowledge ◽  
Biological Effects ◽  
Peripheral Tissues ◽  
Cell Functions ◽  
White Adipocytes ◽  
Obesity And Diabetes ◽  
Regulate Body Weight ◽  
G Protein Coupled

Orexin A and B are two neuropeptides, which regulate a variety of physiological functions by interacting with central nervous system and peripheral tissues. Biological effects of orexins are mediated through two G-protein-coupled receptors (OXR1 and OXR2). In addition to their strong influence on the sleep–wake cycle, there is growing evidence that orexins regulate body weight, glucose homeostasis and insulin sensitivity. Furthermore, orexins promote energy expenditure and protect against obesity by interacting with brown adipocytes. Fat tissue and the endocrine pancreas play pivotal roles in maintaining energy homeostasis. Since both organs are crucially important in the context of pathophysiology of obesity and diabetes, we summarize the current knowledge regarding the role of orexins and their receptors in controlling adipocytes as well as the endocrine pancreatic functions. Particularly, we discuss studies evaluating the effects of orexins in controlling brown and white adipocytes as well as pancreatic alpha and beta cell functions.

Mesophyll conductance: the leaf corridors for photosynthesis

2020 ◽  
Vol 48 (2) ◽  
pp. 429-439 ◽  
Author(s):  
Jorge Gago ◽  
Danilo M. Daloso ◽  
Marc Carriquí ◽  
Miquel Nadal ◽  
Melanie Morales ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Main Role ◽  
Mesophyll Conductance ◽  
Future Studies ◽  
Cell Structures ◽  
Leaf Tissues ◽  
Change Framework ◽  
Chloroplast Stroma

Besides stomata, the photosynthetic CO2 pathway also involves the transport of CO2 from the sub-stomatal air spaces inside to the carboxylation sites in the chloroplast stroma, where Rubisco is located. This pathway is far to be a simple and direct way, formed by series of consecutive barriers that the CO2 should cross to be finally assimilated in photosynthesis, known as the mesophyll conductance (gm). Therefore, the gm reflects the pathway through different air, water and biophysical barriers within the leaf tissues and cell structures. Currently, it is known that gm can impose the same level of limitation (or even higher depending of the conditions) to photosynthesis than the wider known stomata or biochemistry. In this mini-review, we are focused on each of the gm determinants to summarize the current knowledge on the mechanisms driving gm from anatomical to metabolic and biochemical perspectives. Special attention deserve the latest studies demonstrating the importance of the molecular mechanisms driving anatomical traits as cell wall and the chloroplast surface exposed to the mesophyll airspaces (Sc/S) that significantly constrain gm. However, even considering these recent discoveries, still is poorly understood the mechanisms about signaling pathways linking the environment a/biotic stressors with gm responses. Thus, considering the main role of gm as a major driver of the CO2 availability at the carboxylation sites, future studies into these aspects will help us to understand photosynthesis responses in a global change framework.

Prospective Memory Development Across the Lifespan

2020 ◽  
Vol 25 (3) ◽  
pp. 162-173 ◽  
Author(s):  
Sascha Zuber ◽  
Matthias Kliegel
Keyword(s):  
Prospective Memory ◽  
Healthy Aging ◽  
Present Model ◽  
Current Knowledge ◽  
Well Being ◽  
The Elderly ◽  
Cognitive Factors ◽  
Everyday Functioning ◽  
Integrative Framework

Abstract. Prospective Memory (PM; i.e., the ability to remember to perform planned tasks) represents a key proxy of healthy aging, as it relates to older adults’ everyday functioning, autonomy, and personal well-being. The current review illustrates how PM performance develops across the lifespan and how multiple cognitive and non-cognitive factors influence this trajectory. Further, a new, integrative framework is presented, detailing how those processes interplay in retrieving and executing delayed intentions. Specifically, while most previous models have focused on memory processes, the present model focuses on the role of executive functioning in PM and its development across the lifespan. Finally, a practical outlook is presented, suggesting how the current knowledge can be applied in geriatrics and geropsychology to promote healthy aging by maintaining prospective abilities in the elderly.

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