The Related Metabolic Diseases and Treatments of Obesity

Abstract

Obesity is a chronic disease characterized by the abnormal or excessive accumulation of body fat, affecting 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 diseases, chronic kidney disease, and cancers. Factors such as a sedentary lifestyle, overnutrition, socioeconomic status, and other environmental and genetic conditions can cause obesity. Many molecules and signaling 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)/programmed death-ligand 1 (PD-L1), and sirtuin 1 (SIRT1). Commonly used strategies of obesity management and treatment include exercise and dietary change or restriction for the early stage of obesity, bariatric surgery for server obesity, and Food and Drug Administration (FDA)-approved medicines such as semaglutide and liraglutide that can be used as monotherapy or as a synergistic treatment. In addition, psychological management, especially for patients with obesity and distress, is a good option. Gut microbiota plays an important role in obesity and its comorbidities, and gut microbial reprogramming by fecal microbiota transplantation (FMT), probiotics, prebiotics, or synbiotics shows promising potential in obesity and metabolic syndrome. Many clinical trials are ongoing to evaluate the therapeutic effects of different treatments. Currently, prevention and early treatment of obesity are the best options to prevent its progression to many comorbidities.

Keywords: clinical trials; comorbidities; drugs; molecular signaling pathways; obesity; treatment.

Figure 1

Obesity contributes to chronic disease development and progression. Obesity can cause inflammation, dyslipidemia, insulin resistance, hypertension, fat accumulation, vascular endothelium dysfunction, spleen disorder, and gut microbiota dysbiosis. All these conditions are contributing factors to chronic kidney disease (CKD), cardiovascular diseases (CVDs), non-alcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D), and cancers.

Figure 2

Some common molecules and their signaling pathways in the pathogenesis of obesity. Molecules such as NF-κB, TLRs, adhesion molecules, GPCRs, PD-1/PD-L1, SIRT1, and others are commonly involved in the pathogenesis of obesity.

Figure 3

Different metabolic disorders accompany the development and progression of obesity. During the progression of obesity from overweight to severe obesity, it may cause different metabolic disorders, which are associated with the alteration of gut microbiota profiles. In addition, the molecular signaling pathways (Figure 2) may also change during the progression of each obesity-associated comorbidity.

Figure 4

Strategies for obesity treatment. Exercise and dietary change or restriction are commonly applied to prevent and treat the early stage of obesity. Bariatric surgery is a commonly applied treatment for server obesity. Medicines such as semaglutide and liraglutide can be used as monotherapy or a synergistic treatment together with lifestyle management. In addition, psychological management, especially for patients with obesity and distress, is a good option. Gene regulation (microRNAs-mediated therapies) will be applied in the future. Finally, a combination of two therapies or multiple treatments from therapies 1 to 7 can be applied to improve the treatment efficacy.