Effects of Weight Loss on Endothelium and Vascular Homeostasis: Impact on Cardiovascular Risk

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  Figure 1. Different types of adipose tissue. White adipose tissue (WAT) is the most represented type of AT, while brown represents around 4% of total fat and beige 1–2%. White and brown AT originate from cells being different both from the structural and functional standpoints. It has a lower concentration of mitochondria compared to other AT types. WAT directly mediates endothelial dysfunction via the secretion of cytokines and mediators involved in vascular pathophysiology. Brown adipose tissue (BAT) bears a thermogenic action and thus it displays higher numbers of mitochondria. It increases triglyceride clearance and insulin sensitivity and produces mediators involved in the angiogenesis and the lowering of the vascular inflammation, globally playing a cardio- and a vasculo-protective function. Beige adipose tissue is an intermediate entity which appears less detrimental to CV health, with research still ongoing. Upon stimulation, WAT can transform into beige (“WAT browning”), with a mechanism that is reversible upon the stimulus’ withdrawal. The continuous arrows between WAT-beige AT and between BAT-WAT indicate the possibility of AT transformation depending on the presence of…

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  Figure 2. Schematic representation of potential vascular effects of diet-induced weight loss (DIWL). Diet-induced weight loss induces metabolic changes and positively influence endothelial health. After DIWL, a decrease in circulating biomarkers of vascular and endothelial damage is described, together with an improvement in endothelial function and remodelling (increased FMD, decreased pulse wave velocity, increased retinal arteriolar calibre). ↓: decrease; ↑: increase. ICAM-1: intercellular adhesion molecule 1, VCAM-1: vascular cell adhesion molecule 1, PAI-1: plasminogen activator inhibitor 1, VEGF: vascular endothelial growth factor, IL6. Interleukin 6, TNF: tumor necrosis factor, FMD: flow-mediated dilation, PWV: pulse wave velocity. Image created with Biorender (www.biorender.com, accessed on 27 January 2025).

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  Figure 3. Schematic representation of vascular effects of surgery-induced weight loss (SIWL). After bariatric surgery, an improvement in circulating biomarkers involved in vascular homeostasis is observed. Moreover, patients display improved endothelial function (increased FMD, and endothelium-dependent vasodilation) and vascular remodelling, represented by a decrease in intima-media thickness and an increase in brachial arterial diameter. Notably, hybrid surgical techniques exist combining both restrictive and malabsorptive BS. ↓: decrease; ↑: increase. CV: cardiovascular, ICAM1: intercellular adhesion molecule 1, VEGF-A: vascular endothelial growth factor A, PAI-1: plasminogen activator inhibitor-1, FMD: flow-mediated dilation, IMT: intima-media thickness, RYGB: Roux-en-Y gastric bypass, BPD: biliopancreatic diversion. Image created with Biorender (www.biorender.com, accessed on 27 January 2025).

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  Figure 4. The main actions that GLP-1 exerts on the cardiovascular system, based on the available scientific evidence from human and animal models. GLP-1 secretion is stimulated by food transit in the gastrointestinal tract. GLP-1 exerts metabolic and vasculo-protective actions, both contributing to an improvement in the CV outcome. For instance, GLP-1 can increase myocardial glucose uptake and decrease oxidative stress and cardiomyocytes apoptosis, while improving NO release and natriuresis, positively affecting vascular tone. ↓: decrease; ↑: increase. Positive signs in green indicate stimulation. Green arrows indicate production. GLP-1: glucagon-like peptide 1; GLP-1R: GLP-1 receptor; CNS: central nervous system; NO: nitric oxide; RAS: renin angiotensin system; Ang II: angiotensin II. Image created with Biorender (www.biorender.com, accessed on 27 January 2025).

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  Figure 5. The Main actions of ghrelin on the cardiovascular system, based on available scientific evidence from human and animal models. In the conditions of a negative energy balance, ghrelin is produced by the gastric fundus and induces the synthesis of anabolic mediators at the central nervous system level. In parallel, it can impact the CV system. Preliminary data indicate that unacylated ghrelin (UAG) ameliorates vascular endothelial function, as compared to the acylated form (AG), but further research is needed. A crosstalk between ghrelin action and glucose metabolism is observed, as insulin contributes to increased NO bioavailability via the activation of PI3K/Akt pathway, as does ghrelin. ↓: decrease; ↑: increase. Positive signs in green indicate stimulation. Green arrows indicate production. GHS-R: growth hormone segretagogue receptor, GOAT: ghrelin O-acyltransferase, AgRP: agouti-related protein, NPY: neuropeptide Y, ACTH: adrenocorticotropic hormone, GH: growth hormone, IGF-1: insulin-like growth factor 1, NO: nitric oxide, PI3K: phosphoinositide 3-kinase, Akt: Akt serine-threonine protein kinase. Image created with Biorender (www.biorender.com, accessed on 27 January 2025).

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  Figure 6. The main actions adiponectin exerts on the cardiovascular system, based on the available scientific evidence from human and animal models. In healthy conditions, adiponectin is produced by the adipocytes in three isoforms with different molecular weights. The beneficial roles of adiponectin on the cardiovascular system are mediated by three peripheral receptors (AdipoR1 to 3) that are expressed in different cell types, including endothelial cells and vascular smooth muscle cells. Adiponectin can improve endothelial function by directing increasing NO bioavailability and reducing LDL uptake and accumulation within the vascular wall. It can also ameliorate glucose metabolism (indirectly promoting vascular homeostasis) and attenuates negative vascular remodelling via decreased vascular smooth muscle cells migration and proliferation. Ultimately, it blocks NF-kB signalling, reducing vascular inflammation and apoptosis. ↓: decrease; ↑: increase. Green arrow indicates production. ICAM-1: intercellular adhesion molecule 1, VCAM-1: vascular cell adhesion molecule 1, NO: nitric oxide, LDL: low-density lipoprotein, VSMCs: vascular smooth muscle cells, NF-kB: nuclear factor kB, ECs:…

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  Figure 7. The main actions leptin exerts on the cardiovascular system, based on the available scientific evidence from human and animal models. Leptin is mainly produced by adipose tissue in response to increased food intake and insulin levels. Its action is essentially anorexigenic (stimulates satiety), but different effects on the CV system were described—predominantly in animal models—suggesting that only normal leptin values provide CV protection, whereas any other variation from a set point might negatively affect the CV system. Besides, leptin can stimulate sympathetic activity, an action that is maintained even in leptin-resistance conditions. ↓: decrease; ↑: increase. Positive signs in green indicate stimulation. Green arrows indicate production. Blue line indicates inhibition. WAT: white adipose tissue, AgRP: agouti-related protein, NPY: neuropeptide Y, POMC: proopiomelanocortin, LVH: left ventricular hypertrophy, CV: cardiovascular. Image created with Biorender (www.biorender.com, accessed on 27 January 2025).