Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies

Abstract

Obesity is gaining acceptance as a serious primary health burden that impairs the quality of life because of its associated complications, including diabetes, cardiovascular diseases, cancer, asthma, sleep disorders, hepatic dysfunction, renal dysfunction, and infertility. It is a complex metabolic disorder with a multifactorial origin. Growing evidence suggests that oxidative stress plays a role as the critical factor linking obesity with its associated complications. Obesity per se can induce systemic oxidative stress through various biochemical mechanisms, such as superoxide generation from NADPH oxidases, oxidative phosphorylation, glyceraldehyde auto-oxidation, protein kinase C activation, and polyol and hexosamine pathways. Other factors that also contribute to oxidative stress in obesity include hyperleptinemia, low antioxidant defense, chronic inflammation, and postprandial reactive oxygen species generation. In addition, recent studies suggest that adipose tissue plays a critical role in regulating the pathophysiological mechanisms of obesity and its related co-morbidities. To establish an adequate platform for the prevention of obesity and its associated health risks, understanding the factors that contribute to the cause of obesity is necessary. The most current list of obesity determinants includes genetic factors, dietary intake, physical activity, environmental and socioeconomic factors, eating disorders, and societal influences. On the basis of the currently identified predominant determinants of obesity, a broad range of strategies have been recommended to reduce the prevalence of obesity, such as regular physical activity, ad libitum food intake limiting to certain micronutrients, increased dietary intake of fruits and vegetables, and meal replacements. This review aims to highlight recent findings regarding the role of oxidative stress in the pathogenesis of obesity and its associated risk factors, the role of dysfunctional adipose tissue in development of these risk factors, and potential strategies to regulate body weight loss/gain for better health benefits.

FIG. 1.

Conditions generating oxidative stress in the pathogenesis of obesity and the role of oxidative stress in the development of obesity associated health risks.

FIG. 2.

Insulin stimulated signaling cascade of glucose metabolism. Binding of insulin with its receptor (IR) undergoes receptor autophosphorylation and enhances its kinase activity. Subsequent binding of IRS (insulin receptor substrate) with the p85 regulatory subunit of PI3K (phosphoinositide 3-kinase) upregulates the synthesis of PtdIns(3,4,5)P₃ utilizing PtdIns(4,5)P₂ as a substrate. The phosphatase, PTEN (phosphatase and tensin homolog deleted on chromosome 10) dephosphorylates PtdIns(3,4,5)P₃ at the 3′-position. Formation of PtdIns(3,4,5)P₃ activates downstream effector protein molecules, Akt (serine/threonine protein kinase) and PKCζ/λ (protein kinase C zeta/lambda). This causes the translocation of GLUT (glucose transporter) from intracellular site to the plasma membrane followed by glucose uptake and utilization by the cells leading to normoglycemia, control of vascular inflammation, and prevention of CVD (cardiovascular diseases) and the complications of diabetes.

FIG. 3.

Role of dysfunctional adipose tissue in the development of obesity associated health risks.