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Thermoregulation in the circulatory system - Circulatory system physiology - NCLEX-RN - Khan AcademyThermogenesis and cardiovascular health -
Angiotensin-converting enzyme 2 ACE2 , which is widely recognized as the entry receptor for SARS-CoV-2 into host cells , is expressed in human EAT The downregulation of ACE2 levels increases EAT inflammation, whereas treatment with angiotensin 1—7 reduced EAT inflammatory cytokines in a mouse model The modulation of ACE in EAT might, therefore, have a role in COVIDrelated myocardial and perivascular inflammation.
ACE inhibitors could be a potential component of therapy for these sequelae of COVID, although data are still insufficient and controversial EAT of patients hospitalized with severe or critical COVID shows signs of increased inflammation on CT, irrespective of whether CAD is present 32 , , , In patients with COVID, EAT density on CT is markedly elevated at hospital admission and decreases to normal at discharge, whereas subcutaneous fat shows no signs of inflammation EAT inflammation decreased in patients with COVID who received oral or intravenous dexamethasone, whereas no significant changes in inflammation were observed with other COVID therapies Therefore, EAT might have a role in COVIDrelated cardiac syndrome, and CT-measured EAT attenuation could be a marker of inflammation and severity of COVID The physiology and pathophysiology of EAT and their clinical implications form a fast-moving and productive field of research.
EAT is a measurable and modifiable cardiovascular risk factor that adds qualitative value to the stratification of cardiovascular risk. Assessment of EAT, with commonly used imaging techniques, such as echocardiography, CT and MRI, should be readily accessible to contemporary cardiologists.
EAT provides a novel and unconventional perspective on the pathophysiology of major cardiovascular diseases. EAT directly contributes to the development and progression of CAD, mainly by causing inflammation but also by endothelial damage and oxidative stress as well as the accumulation of glucose and lipids in the proximal coronary arteries.
In the context of atrial fibrillation, EAT represents a new pathogenic substrate through the regional secretion of factors that induce fibrosis and neurohormonal disarray of the atrial myocytes. The role of EAT in heart failure is mediated through several pathways, including the excessive release of fatty acids leading to intracardiac cell ectopic lipid accumulation, overexpression of local pro-inflammatory and profibrotic cytokines with pro-arrhythmogenic properties, and increased β-adrenergic receptor activation.
Pharmacological modulation of EAT induces previously unexpected beneficial cardiometabolic effects. The potential to restore the cardioprotective function of EAT with targeted agents, such as GLP1R agonists and SGLT2 inhibitors, can open new avenues in pharmacotherapy for cardiovascular diseases.
Several challenges remain for research on EAT. Further investigations are needed to determine whether reducing the mass of EAT can help to improve or eliminate atherosclerosis or prevent the development of atrial fibrillation and heart failure.
The potential for pharmacological manipulation of the EAT transcriptome to restore its physiological and protective properties is a fascinating concept but is yet to be demonstrated.
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Diabetes 63 , — Reassuringly, although obese individuals showed blunted expression of thermogenic genes in BAT 78 and decreased glucose uptake by the tissue, 79 adipocyte progenitors isolated from BAT of obese individuals can differentiate into thermogenic adipocytes at an equal frequency as those isolated from lean individuals, and the resulting differentiated brown adipocytes displayed comparable basal and noradrenalin-stimulated mitochondrial respiration.
Besides the observed beneficial relation between the presence of BAT and CVD in humans see Section 6 , cold exposure has been shown to beneficially affect several risk factors for CVD, including adiposity and insulin resistance. Adiposity results from excessive energy intake relative to energy expenditure, or alterations in nutrient partitioning.
Acute cold exposure increased resting energy expenditure in both lean 81—83 and obese 84 participants, and notably such increases were only evident 82 or more pronounced 83 in BAT-positive individuals i.
with detectible [ 18 F]FDG uptake by BAT depots. Even though BAT activity is generally assessed using the glucose tracer [ 18 F]FDG, the cold-induced increase in energy expenditure was mainly explained by an increase in lipid oxidation.
L and TAK did not reduce body fat mass. Alternatively, it is well possible that BAT activity simply improves overall metabolic health, rather than reducing adipose tissue mass per se.
In line with this notion, a very recent study has suggested that after correcting for BMI, the presence of active BAT, as measured by [ 18 F]FDG uptake, was associated with decreased visceral adipose tissue and increased subcutaneous adipose tissue, 91 a phenotype that is typically associated with better metabolic health.
BAT has also been implicated in glycaemic control. In healthy lean humans, acute cold stimulation 18°C 92 or 1-month cold acclimation i. Thus, studies have unequivocally demonstrated that cold exposure activates BAT, enhances energy expenditure, and improves glycaemic control.
The relative contribution of BAT and other metabolic organs needs to be better understood, but at the very least it seems that the presence of cold- activate d BAT is associated with metabolic health.
In , Cypess et al. Indeed, transcriptomic analysis of human BAT biopsies showed that abundance of β 2 -AR far exceeds that of β 3 -AR, while β 3 -AR is the dominant AR in mouse BAT. The recent finding regarding the prominent role of β 2 -AR in human BAT activation, however, opened up new opportunities for BAT as a therapeutic target in cardio metabolism.
Interestingly, the amino acid sequence of human β 2 -AR is highly polymorphic. These findings thus imply that β 2 -AR agonism may be the way forward in adrenergic BAT activation, and further studies are warranted to assess whether this can effectively and safely activate human BAT in vivo.
Besides cold-mediated sympathetic stimulation and pharmacological β-AR agonism, stimulation of two hormonal pathways also potently activate BAT and are worth noting as they lower atherosclerosis in preclinical models and improve risk factors for CVD in humans see also the graphical summary in Figure 3.
Firstly, treatment of mice with recombinant human FGF21 enhanced the uptake of glucose and triglyceride-derived FAs from TRLs by BAT and promoted WAT browning, , which normalized glycaemia and reduced plasma triglycerides. Graphical summary of promising therapeutic interventions to promote thermogenic adipose tissue activity and their effects on risk factors for CVD in humans.
Similar to FGF21, studies of glucagon-like peptide 1 receptor GLP-1R agonism have also shown promising results. In lean mice, intracerebroventricular administration with the GLP-1R agonist liraglutide activated BAT thermogenesis as evident from decreased intracellular lipid content in combination with increased interscapular temperature In both lean and diet-induced obese mice, another GLP-1R agonist, exendin-4, was shown to increase UCP1 protein content in BAT.
Indeed, patients with type 2 diabetes using liraglutide showed less death from cardiovascular causes and a lower frequency of nonfatal myocardial infarction and stroke.
CETP mice have shown that GLP-1R agonists reduced atherosclerosis development via reducing inflammation in atherosclerotic plaques. Furthermore, glucose-dependent insulinotropic polypeptide receptor GIPR agonism was proposed to enhance the metabolic effects of GLP-1R agonism.
Taken together, there is compelling evidence for a relationship between the presence of metabolically active BAT in humans and lower CVD risk. The still unresolved question, however, is to what extent the observed associations imply causality or merely reflect overall metabolic health.
Cold interventions have been shown to activate BAT activity and thermogenesis, and large prospective intervention studies applying cold interventions will be needed to prove causality. In addition, genetic polymorphisms determining the thermogenic capacity of adipose tissue may be identified to allow proof of causality between adipose tissue thermogenesis and CVD risk in large Mendelian-randomization studies.
Experimental studies in mice have convincingly shown that thermogenic activity in adipose tissue enhances lipolytic processing of TRLs, resulting in FA uptake by adipocytes and consequently promotes liver uptake of TRL remnants provided that an intact human-like ApoE-LDLR pathway is present Table 1.
Together, these result in combined attenuation of hypertriglyceridaemia and hypercholesterolaemia and reduce atherosclerosis development.
This anti-atherosclerotic effect is likely further enhanced by elevated reverse cholesterol transport, which is driven by enhanced cholesterol efflux capacity of HDL as a consequence of increasing lipid transfer from TRLs to HDL during lipolytic processing.
In humans, BAT activity inversely correlates with circulating triglyceride and HDL-cholesterol levels and CVD prevalence and seems to protect against additional risk factors for CVD including adiposity and insulin resistance. Combined with the findings from preclinical studies that thermogenic adipose tissue activation adds to the lipid-lowering and antiatherogenic effects of classical lipid-lowering strategies i.
Obviously, further research is needed to reveal whether promotion of BAT activity or browning of WAT can be used to treat dyslipidaemia and atherosclerotic CVD in humans, especially in those individuals who are at high risk for CVD.
FGF21 and GLP-1R agonism likely in combination with GIPR agonism activate BAT and promote browning of WAT in mice and are promising therapeutic strategies to treat human atherosclerotic CVD.
Further clinical studies are warranted to assess their efficacy to reduce atherosclerotic CVD, as well as the involvement of BAT activation therein. Also, the recent discovery that human brown adipocytes are mainly activated via β 2 -AR stimulation, in contrast to mouse brown adipocytes that are activated mainly through the β 3 -AR, 15 provides a unique opportunity to assess both the efficacy and safety of β 2 -AR agonism in human BAT activation in relation to cardio metabolic health.
This work was supported by the Dutch Heart Foundation [T to S. is supported by a full-time PhD scholarship from the China Scholarship Council. Nedergaard J , Bengtsson T , Cannon B.
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Identification of inducible brown adipocyte progenitors residing in skeletal muscle and white fat. A large recent study revealed that the presence of metabolically active BAT in humans is associated with lower triglycerides, higher HDL-cholesterol and lower risk of cardiovascular diseases.
This narrative review aims to provide leads for further exploration of thermogenic adipose tissue as a therapeutic target. To this end, we describe the latest knowledge on the role of BAT in lipoprotein metabolism and address, for example, the discovery of the β2-adrenergic receptor as the dominant adrenergic receptor in human thermogenic adipocytes.
Keywords: Adipose tissue; Atherosclerosis; Cardiovascular disease; Dyslipidaemia; Non-shivering thermogenesis.
Thermogenesis Thermogenesis and cardiovascular health a role in Elevate your stamina metabolism Thermogenesid regulation of body temperature, Thermogendsis are key aspects of cardiovascular health. Thermogenesis cardiovasculae increase heart rate as Thermogenesis and cardiovascular health body works to produce heat, thereby increasing cardiovascular load. Increased body heat production through thermogenesis can lead to increased blood pressure. Thermogenesis often leads to vasodilation to dissipate heat, affecting blood flow and pressure. How can thermogenesis-induced sweating affect cardiovascular health? Sweating leads to fluid loss, which if not replenished, can lead to dehydration and strain on the cardiovascular system. Thermogenesis is a key mechanism to maintain body temperature within a narrow range, important for overall bodily functions, including cardiovascular health. Thank you for cardiocascular nature. You Thermogenesis and cardiovascular health using a Thermogeneis version with limited Dietary restrictions in sports performance for CSS. To obtain the best Thermogenesis and cardiovascular health, we recommend you use a more up to cardiofascular browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Interest in epicardial adipose tissue EAT is growing rapidly, and research in this area appeals to a broad, multidisciplinary audience. EAT is unique in its anatomy and unobstructed proximity to the heart and has a transcriptome and secretome very different from that of other fat depots. EAT has physiological and pathological properties that vary depending on its location.
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