Metabolic Syndrome

Metabolic syndrome (MetS) is a combination of health disorders that mainly result from overweight and obesity. It increases the risk of developing cardiovascular disease and diabetes. (MetS) closely related to the existence weight gain or Obesity and laziness. It increases the serum levels of TNF-α and change the levels of a number of other parameters (e.g., adiponectin, resistin, and PAI-1). TNF-α dose not only appear to cause the production of inflammatory cytokines. It can trigger cell signaling by interacting with TNF-α receptors that can lead to insulin resistance. Usually, the digestive system molders the foods you eat and converts them to glucose. Insulin is an anabolic hormone produced by the pancreas that aids glucose get in your cells. To be utilize, as an energy source .Cells do not respond to insulin normally, and sugar cannot easily enter cells in people with insulin resistance. As outcome, blood glucose rises, until the body produces more insulin in an attempt to lower blood sugar. The following factors increase the chance of developing MetS as age increases the risk of developing MetS with age and ethnicity. In the United States, it appears that women of Mexican descent are more likely to develop MetS. Obesity carrying an extra amount of weight, especially in the abdomen, increases the risk of MetS. From this review, it stated that metabolic syndrome stands for the constellation of cardiovascular risk factors that raise the risk of cardiovascular arteriosclerosis and type 2 diabetes. Type 2 diabetes is a major global public health issue with more than 300 million people projected in 2025. Ibn Al Haitham Journal for Pure and Applied Science Journal homepage: http://jih.uobaghdad.edu.iq/index.php/j/index Doi: 10.30526/34.3.2675 Article history: Received 23 March 2021, Accepted 1 June 2021, Published in 2021. Department of Chemistry/ College of Education, for pure Science(Ibn-Al-Haitham) University of Baghdad. Iraq noorhan.albayaty@gmail.com Department of Chemistry/ College of Education, for pure Science(Ibn-Al-Haitham) University of Baghdad. Iraq drbiochem2007@gmail.com Department of Chemistry/ College/ Faculty of Dentistry / University of Kufa. tamara.hussein@uokufa.edu.iq Ibn Al-Haitham Jour. for Pure & Appl. Sci. 34(3)2021 27


1.Introduction
Metabolic syndrome (MetS) in individuals sensitive to cardiovascular disease (CVD) and Type 2 diabetes (T2DM) had been theorized in accordance with a constellation of risk factors like high rapid blood glucose, atheragenic dyslipidemia, high blood pressure, and abdominal obesity [1]. Guidelines were developed by means of readily existing clinical variables for a clinical and epidemiological managing of MetS. [2]. Several researches have shown that MetS and its constituents were strongly related to a risk of Type 2 diabetes incident [3]. A resistance to insulin, metabolic syndrome, and prediabetes were closely related and overlap. Underlying disorder in energy usage and storage was thought to be the cause of the syndrome. The cause a continuous medical research [4,5].
Metabolic syndrome began as a conception instead of a diagnosis [6]. The metabolic syndrome began in 1920 with the high blood pressure (hypertension), huge blood glucose (hyperglycemia) and gout associated to Kylin, a Swedish physician [7].
After that in 1947, Vague defined a common link between visceral obesity and the metabolism found in CVD and T2DM [3,8]. After this, in 1965, Avogaro and Crepaldi [9] depicted syndrome in their study based on hypertension, hyperglycemia and obesity, which was presented at an annual European Association for Diabetes Studies (ESDS). After a 1988 lecture on the role of insulin resistance in human diseases identified by Reaven, the field has progressed significantly [10]. He called it "Syndrome X" and described it as "a cluster of risk facilities for cardiovascular and diabetes disease." Introducing a concept of insulin resistance was his main contribution. Nevertheless, a definition had been later added as a crucial abnormality abnormally lacked obesity or visceral obesity.
For the combination of high body obesity, intolerance of glucose, hypertriglyceridemia and hypertension. Kaplan [11] renamed the "Deadly Quartet" syndrome, but again in 1992, it had been renamed as "The Insulin Resistance Syndrome" [12]. Many groups tried to advance diagnostic standards for MetS diagnosis [13]. The initial attempt had done in 1998 by a diabetes group of the World Health Organization (WHO) to define MetS [14]. In reply, the European Insulin Resistance Study Group (EGIR) in 1999 rejected an amendment to the definition of WHO [15]. The National Adult Treatment Panel Cholesterol Education Program (NCEP/ATP) launched its definition in 2001 [16]. The American Association of Clinical Endocrinologists (AACE) subsequently presented its points of view in 2003 on the syndrome definition [17].

2.Pathogenesis of Metabolic Syndrome
Intensive research is intended to underlay mechanism through which the MetS elements share aspects of their pathophysiology. The ability of the adipose tissue in its pathophysiology is essential for the development and storage of energy substrates. But other metabolic pathways should be used since the same metabolic malfunctions in lean individuals could occur in MetS [18]. Systems biology approaches and the development of new global models are crucial for omics-based research [19]. This is the case for recent system biology studies in non-alcoholic steatohepatitis patients [20]. The involvement of various methods (de novo lipogenesis, beta oxidation, pyruvate use and serine and glutathione synthesis) was identified based on this approach. In some cases, the excess energy flow measures presented in the MetS are managed and prevent oxygen roots from accumulating. In addition, it identifies the critical role of the liver red cell (PKLR) in triglyceride accumulation in the liver [21]. In sum, the complementary mechanisms prevailing in most groups are lip toxicity, low-grade chronic inflammation, and insulin resistance. His description extends beyond this review's scope. The outstanding reviews in the references section will provide interested readers with a description of the art of this field [22][23][24][25][26].

3.Metabolic Syndrome and Angiotensinogen
The renin-angiotensin (RAS) precursor is transformed to angiotensin I and angiotensin II through the enzyme cascade (AGT) by renin and angiosin-conversion (ACE) actions, correspondingly. Ang (1-7) consists of Ang I and Ang II of ACE2. Ang II is associated with high blood pressure and several inflammatory illnesses, involving cardiovascular and kidney disease, dyslipidemia and metabolic syndrome. AGT is extremely stated in adipose tissue and separated by mature adipocytes in human and animal models from separate adipose deposits [28]. Rodents are capable of producing up to 30% of the circulating AGT levels in vivo [29], in disagreement for the role of paracrine AGT adipose and the new views of the endocrine tissue. Adipose AGT may as well have autocrine influences, because all components including renin, ACE and ACE2 are expressed in adipose tissue. This allows for local Ang II and other adipose tissue angiotensin peptides to be produced. [30,31].
The receptors of angiotensin both adipocytes and preadipocytes include the Type 1 Ang II (AT1) and 2 (AT2) receptors and Ang IV (1-7) (MasR) [32]. (Apprentice) C-reactive protein is the best featured and well standardized inflammatory biomarker C-Reactive Protein (CRP) Many reported studies have now confirmed that in MetS patients, CRP levels were high. In addition, high-sensitivity CRPs (hsCRPs) were proposed as a clinical criterion for the development of MetS and hsCRP-modified risk rating for CHDs [33].
In addition, Yudkin et al [34], contained a highly significant correlation among inflammatory indicators and some feasibility of the MetS in 107 non-diabetic patients and conducted Z-score analytic. Insulin resistance calculation based on HOMA, BP, low HDL, triglycerides, and proinflammatorial cytokins, IL-6 and tumor necrosis factor (TNF) was shown to be strongly linked to levels of CRP. The strongest determinants of inflammatory condition were BMI and insulin resistance. The number of metabolic characteristics and the hsCRP levels were linearly linked.
In addition, Festa et al [35], have shown that hsCRP was positive in BMI, waist circumference, BP, triglycerides, cholesterol, LDL cholesterol, plasma glucose, and fasting insulin correlating with HDL cholesterol and insulin sensitivity index, in the Insulin Resistance and Atherosclerosis Studies (IRAS). CRP levels, the central adiposity and insulin resistance were most closely related.
The NHANES III study [36] has been the largest study to date examining the relationship between inflammation and the MetS. The MetS patient with ATPIII criteria was more likely than patients without the syndrome to have elevated inflammation markers like CRP, fibrinogens, and leucocytes, in the typical sample of the US population (8570 participants above 20 years old). ATPIII criteria were used. Therefore, the amount of metabolic features and the growing levels of hsCRP appeared to be clearly related. Furthermore, in predicting MetS using receptors operating features (ROF) testing, we have shown that CRP values were consistent with the ratio of high-molecular weight (HMW) adiponectin to CRP [37].
In several metabolic processes as autocrine and paracrine functions of adipocyte function, IL-6 (pleiotropic cytokine) plays important roles [38] .Currently, accumulating evidence shows that IL-6 has a strong connection to metabolic disorders like MS and diabetes of type 2. In the meantime, IL-6 elevation in adipose tissues in diabetes mellitus or in patients with obesity was documented, particularly in those with MS characteristics [39] .
Eckel et al., considered that the increase in IL-6 in MS appeared to act on several important factors that contributed to insulin resistance, increased liver glucose production, insulin-mediated glucose absorption in the skeletal muscle, and facilitated hypertension [40] Moreover, the polymorphism of the IL-6 gene was considered an aggravating factor in cardiovascular development and progression. [41]. The report of the Council of Europe Lectin-likes LDL has been the receptor of atherogenic low-density lipoprotein (Ox-LDL) that was not constitutive, but dynamically induced by proinflammatory stimuli, angiotensin II or Ox-LDL which affected atheroscleric growth and plate vulnerability [42,43].
The long-lasting depression (LLD) receptor long-lasting depression (LLD)-1 receptor receptor is a receptor that affects both atherosclerotic progression and plaque vulnerability. Lectin-Like Oxidized Low-Density Lipoprotein Receptor (LOX-1) occurs prominently in intimate smooth muscle cells and lipid-laden macrophages in advanced plaques in human atherosclerotic lesions [44]. Moreover in the production of matrix metalloproteinases, which can straightforwardly be connected to plaque risk and rupture, LOX-1 also plays a major role in Ox-LDL-induced apoptosis of the endothelial and smooth cells [45][46][47]. In addition, LOX-1 expression has been connected with the instability in the hypercholesterolemic pattern of atherosclerotic plaques [48][49][50].
An activated systemic RAAS is critical for the pathogenesis of HTN and other CRS components in insulin resistance states such as obesity [51]. Increasingly, expanded visceral and adipocyte perivascular tissue is essential to activate the RAAS. The production of angiotensinogen by adipocyte can contribute up to 30% of angiotensinogen circulating [52]. The idea that angiotensinogen adipocyte production contributes to an activated RAAS is enhanced by observations of angiotensinogen knock-out mousses that are immune to obesity, insulation and HTN development [53,54].
There has been no obesity-related HTN in other murine studies of the ablation of adiposederived angiotensinogen. (55) This evolving research highlights the important connection between angiotensinogen derived from adipocytes and HTN, particularly in the context of CRS [56].
There is growing evidence that adipocytes are a major source of extra-adrenal aldosterone [57]. The observation that obese people, in particular females, have increased aldosterone circulation supports this concept [58]. Studies have shown that the activation of aldosteroneinduced mineralocorticoid receptors (MRs) in vascular tissues can itself be an instigator in promoting oxidative stress, inflammation, immune modulation and fibrosis in vascular tissue This MR activation can therefore be a therapeutic aim to prevent developments in dietary obesity in vascular rigidity and HTN. [59].
Metabolic syndrome stands for the collection of cardiovascular risk-associating disorders is associated with obesity. Metabolic syndrome is linked to overproduction (ROS). ROS helps to link metabolic syndrome and salt-sensitive hypertension, both are caused by obesity and the excess of salt intake and significant risks to health in advanced countries. ROS can cause insulin resistance, an essential element in metabolic syndrome development, and saltsensitive hypertension promotes ROS production, thereby encouraging metabolic syndrome development. In addition, ROS activates (MRs) and a sympathetic nervous system that can contribute to metabolic and salt-sensitive hypertension syndrome development. In animal models with metabolic Syndroma, salt-induced progression of (CVD), probably due to further ROS stimulation and subsequent ROS-induced active MR and sympatric arousal, is also accelerated. ROS thus contributes to the development of a metabolic syndrome itself and the accompanying CVD, especially when consuming excessive salt [60][61][62][63].
The finest candidate for the highest destructive periodontal disease in obesity or metabolic syndrome is (TNF-α). In both obesity and metabolic syndrome, TNF-α levels are systemically elevated [64]. Researches about human and animal models in the 1990s had depicted that adipocytes secrete TNF-α and therefore excess fat in obesity leads to chronic systemic swelling [65]. In addition, TNF-α was reported to induce diabetes and obesity to resist insulin [66]. It is known that a chronic systemic inflammation in the obesity is also influenced by other cytokines from adipic tissue (67).

4.Management and Treatment
Overweight and obesity, physical inactivity and atherogenic diet are the underlying risk factors that promote the growth of metabolism. Every current Guideline on Management of (MetS) Components emphasizes that the first line of treatment is lifestyle modification [68].
In an attempt to highlight the need for more intensive lifestyle therapy to prevent CVDs in higher risk patients, ATP III included the concept of metabolic syndrome in its cholesterol guidelines [69].
A target blood pressure for a general population must be 140/90mmHg, and the target for diabetes mellitus patients should be less than 130/80mmHg, according to the recent guidelines for the Joint National Committee (JNC). The recent guidelines from the Joint National Committee-8 have also indicated that the target should be less than 150/90 mmHg in patients aged 60 or older [70].
Tests should include the check-up on full-flow analytic fat, thyroid stimulating hormone level, urinalysis, and liver function tests in patients with hypertriglyceridemia defined by triglycerides over 150 mg/dL. Patients must first be advised on lifestyle variations, involving withdrawal from smoking, loss of weight and diet and changes to exercise, following an extensive analysis.
Doctor treatment begins with hypertriglyceridemia once a level is greater than 500 mg/dL and patients typically have a mixed disorder of dyslipidemia by then. Patients are usually first treated for moderate to high-intensity statins but also for the treatment of hypertriglyceridemia fibrates, niacin and omega acids are as well available. Higher LDL must also be managed too much in patients, in particular when a risk of ASCVD is above 7.5%, which determines the 10-year ASCVD risk of the patient. The goal is to decrease LDL by 50 % in those patients with high-intensity statin treatment [71].
Bariatric surgery can be used in patients with severe obesity. The most efficient singletherapy metabolic syndrome is considered a bariatric surgery. Laparoscopically adjustable gastric banding, laparoscopic gastric circumvention of Roux-en-Y and laparoscopic gastric sleeves are the most frequent procedures. In patients with BMI daily at 40 kg/m 2 or with a BMI daily 35 kg/m 2 or in other comorbidities, bariatric surgery is recommended. In order to avoid operative, nutritional and psychiatric complications, patients need a longterm follow-up after surgery [72].

5.Conclusion
Metabalic syndrome stands for the constellation of cardiovascular risk factors that raise the risk of cardiovascular arteriosclerosis and type 2 diabetes. Type 2 diabetes is a major global public health issue with more than 300 million people projected in 2025. Therefore, the tide of this dangerous trend will help to stop the risk stratification, early identification and radical intervention.