Review: cell mechanisms in the control of inflammatory foundations of obesity and secondary metabolic disorders

Review: Obesity is a global threat to human health that is precipitating epidemically, with almost 2 billion adults categorised as overweight or obese in 2016. Ireland has one of the highest reports of obesity in Europe with 60% of Irish adults reported as overweight or obese. Inflammation plays an integral role in disease pathogenesis and is a major hallmark of obesity and obesity-related secondary co-morbidities. Obesity-related inflammation can precipitate several diseases, such breast cancer, insulin resistance, type II diabetes and cardiovascular issues. As obesity puts human health at inherent risk, the regulation of obesity-related inflammation is therefore a necessary component to reduce disease onset, and progression, and manage symptoms. Targeting key mediators in the chronic low-grade inflammation seen in obesity may provide insight into novel obesity treatment and management approaches. For example, targeting cytokine regulation is key to regulating inflammation, by reducing the expression of pro-inflammatory cytokines, and increasing the expression of anti-inflammatory cytokines. The most common approach to obesity management and treatment includes clinical and pharmacological interventions, focusing on avenues such as surgery, weight loss management programs, and synthetic medications like semaglutides (e.g. Wegovy) and glucocorticoids (e.g. dexamethasone). The complex clinical and regulatory history of these anti-obesity avenues has derived the investigation into alternative strategies utilising natural resources. Consequently, research into the anti-inflammatory and anti-obesity properties of compounds like curcumin has heightened in recent years. Curcumin is a promising therapeutic approach in regulating inflammatory disease through the modulation of key disease mediators, such as pro- and anti-inflammatory cytokines, microRNAs (miRNAs) responsible for gene expression, and intracellular signalling pathways. Although the potential therapeutic benefits of curcumin are significant, there are several unknowns and limitations to its activity that remain. This review will journey through the inflammatory foundations of obesity, providing information on anti-obesity strategies currently available and closing with curcumin as an alternative natural therapeutic approach to treating obesity.