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What Health Risks Are Associated With Obesity
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The Weight Debate: Obesity And Health Risks
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Received: 8 August 2022 / Revised: 19 August 2022 / Accepted: 23 August 2022 / Published: 25 August 2022
Obesity is a chronic disease characterized by abnormal or excessive accumulation of body fat, which affects more than 1 billion people worldwide. Obesity is commonly associated with other metabolic disorders, such as type 2 diabetes, non-alcoholic fatty liver disease, cardiovascular disease, chronic kidney disease and cancer. Factors such as lifestyle, excess nutrition, socioeconomic status and other environmental and genetic conditions can lead to obesity. Many signaling molecules and pathways are involved in the pathogenesis of obesity, such as nuclear factor (NF)-κB, Toll-like receptors (TLRs), adhesion molecules, G protein-coupled receptors (GPCRs), programmed cell death 1 (PD- ). 1) / ligand programmed death 1 (PD-L1), and Sirtuin 1 (SIRT1). Commonly used obesity management and treatment strategies include exercise and dietary changes or restrictions for the early stages of obesity, bariatric surgery for severe obesity, and Food and Drug Administration (FDA) approved drugs such as semaglutide and liraglutide that can be used as monotherapy or as A synergistic treatment. In addition, psychological management, especially for obese and distressed patients, is a good option. The gut microbiota plays an important role in obesity and its comorbidities, and reprogramming the gut microbiota with fecal microbiota transplantation (FMT), probiotics, prebiotics or synbiotics shows promising potential in obesity and metabolic syndrome. Many clinical trials are underway to evaluate the therapeutic effects of various treatments. Currently, prevention and early treatment of obesity is the best option to prevent its development in many co-morbidities.
Gut Microbiome Insights; Obesity And Digestive Health Risks; Delivery Options And Predictors Of Failure For Fecal Microbiota Transplantation; Among Featured Topics Presented At The American College Of Gastroenterology’s 80th Annual Meeting
Obesity is a chronic disease characterized by abnormal or excessive accumulation of body fat. The body mass index (BMI) is calculated as the weight in kilograms divided by the square of the height in meters (kg/m)
) [1]. According to data from the World Health Organization (WHO), more than 1 billion people in the world are obese, including 650 million adults, 340 million adolescents and 39 million children, which will cause around 167 million people to fall ill in 2025. 2 ] . The prevalence of obesity is influenced by many genetic and environmental factors, such as gender, race, physical activity, diet and socioeconomic status [3]. For example, a study in Japan showed that the prevalence of obesity in men was 27.2%, higher than in women (10.6%) [4]. In addition, personal or social background, including marital status, welfare registration, and current economic conditions, was associated with obesity status in women, but not in men [4].
Many conditions can cause obesity, including a sedentary lifestyle, excess nutrition, socioeconomic status, environment, and genetic factors [5]. For example, the COVID-19 pandemic has contributed to an increase in obesity rates due to increased sitting time and food consumption, as well as a lack of socioeconomic activity [6]. Genes encoding leptin (LEP), leptin receptor (LEPR), melanocortin receptor 4 (MC4R), proprotein convertase subtilisin/kexin type 1 (PCSK1), proopiomelanocortin (POMC), suppressor kinase Ras 2 (KSR2), adenylate cyclase 3 (ADCY3 ) ), and others contribute to the development and progression of obesity [7]. For example, mutations in the ADCY3 gene lead to obesity in children of Pakistani descent, whereas heterozygous mutations are associated with the severity of obesity in children of European-American descent [8]. In addition, ADCY3 variants are associated with a significantly increased risk of obesity and T2D in the Greenlandic population [9]. ADCY3 mutations play an important role in the primary cilia of nerves (microtubule-based cellular organelles) in neuronal function, leading to a tendency to obesity [10].
Obesity is commonly associated with many other metabolic disorders, including type 2 diabetes (T2D), non-alcoholic fatty liver disease (NAFLD), cardiovascular disease (CVD), chronic kidney disease (CKD), and cancer [ 11 , 12 ]. In addition, obesity is positively related to the severity and mortality of coronavirus disease 2019 (COVID-19) in patients [13]. Adipose tissue secretes many inflammatory cytokines such as tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), which are the main group of factors that cause metabolic disorders [14]. Obesity also causes other complications, such as dysfunction of vascular epithelial cells and accumulation of lipids in organs other than adipose tissue. In the following sections, the many factors that contribute to obesity-related comorbidities will be reviewed. Next, the molecular signaling pathways involved in the pathogenesis of obesity are discussed. Finally, current management and treatment options for obesity are summarized.
Vitamin D Deficiency: A Potential Risk Factor For Cancer In Obesity?
Obesity, directly and indirectly, contributes to many other chronic disorders, including CKD, CVD, NAFLD and T2D, as well as cancers, such as hepatocellular carcinoma (HCC) [15]. For example, the prevalence of NAFLD in obese patients can be as high as 70-90%, and is positively related to BMI (≥35) [16]. Inflammation, insulin resistance and metabolic dysfunction caused by obesity impact the mortality and morbidity of this chronic disease. In this section, we review some of the common obesity-related comorbidities and their associated causes.
CKD is a leading public health problem in the world, affecting around 13.4% of the world’s population. The most common symptoms in CKD patients include sleep disturbance, weakness, fatigue, pain and itchy skin [17]. Progression of CKD can lead to end-stage renal disease, leading to increased renal replacement [18]. Obesity contributes to CKD by increasing intrarenal fat deposition, impaired glomerular filtration rate and albuminuria [19]. In addition, obesity-related local and systemic inflammation, insulin resistance, fibrogenesis, and gut microbiota dysbiosis are also associated with the development and progression of CKD [ 20 , 21 , 22 ]. Overweight and obese people with metabolic disorders are more likely to develop CKD [23]. Therefore, weight control and a healthy diet are recommended for obese people.
Obesity-related factors including dyslipidemia, hypertension, insulin resistance, vascular endothelial dysfunction, and sleep disturbances may contribute to CVD [ 24 , 25 ]. Obesity-related co-morbidities such as CKD and NAFLD also contribute to CVD [ 26 , 27 ]. For example, chronic, low-grade obesity-related inflammation in metabolic tissues (eg, adipose tissue and liver) alters the expression of adipocytokines and lipoproteins such as adiponectin and high-density lipoprotein (HDL), which affect energy metabolism and lead to endothelial . Dysfunction. increase the risk of CVD [28]. In addition, adipose tissue can secrete many other adipocytokines, such as leptin, resistin, visfatin, TNF-α, and IL-6 [ 29 ]. Their roles vary in the pathogenesis of CVD. Adipocytokines such as omentin and adiponectin, which are secreted from visceral adipose tissue (VAT), have an anti-inflammatory function. They can regulate nitric oxide (NO) production in endothelial cells and inhibit vascular calcification to prevent atherogenesis and inflammation [30]. In contrast, resistin and TNF-α expression contribute to insulin resistance in obesity and T2D. IL-6 is an important cytokine in myocardial lipid accumulation [29]. Blocking expression of IL-6 or its receptor by interfering with IL-6 signaling pathways results in a reduced risk of coronary artery disease and atrial fibrillation, as well as T2D [31].
NAFLD is the most common type of chronic liver disease, affecting more than 25% of the world’s population [ 32 , 33 ]. NAFLD is a risk factor for T2D, CVD and HCC. A large cohort study demonstrated that overweight and obesity are positively and strongly associated with the prevalence of NALFD in metabolically healthy men and women, with multivariable adjusted mean hazard ratios of 2.15 and 3.55, respectively [34]. The prevalence of NAFLD and NASH will increase in many countries, as predicted in models based on the prevalence of obesity and T2D [35]. Many obesity-related factors can contribute to NAFLD and its development in non-alcoholic steatohepatitis (NASH), including subcutaneous white adipose tissue (SCWAT) dysfunction [36], insulin resistance [37], inflammation [38], intestinal microbiota dysbiosis [39 ] ], and imbalances in energy metabolism [ 40 ].
Health Hazards Associated With Overweight And Obesity
Although obesity is a contributor to NAFLD, lean NAFLD patients also have a higher risk of liver-related death compared to obese and overweight subjects [41]. The lean NAFLD patients have no accumulation of visceral fat (abdominal fat), with less fibrosis and a lower prevalence of T2D compared to obese patients, but are generally dyslipidemic [42].
T2D is a chronic disease with
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