Current Trends in the Epidemiology of Obesity and the Association Between Obesity and Metabolic Liver Disease (MASLD/MASH)

Excess adiposity and obesity are increasingly prevalent, with incidence rising in many parts of the world; both trigger a state of metabo-inflammation in adipose tissue, creating a systemic milieu characterised by insulin resistance and pro-inflammatory and fibrogenic states. Along with systemic inflammatory cues, perturbations in systemic and individual organ metabolic homeostasis result in metabolically driven cell stress, injury and death; this activates innate immune signals promoting fibrogenesis and organ dysfunction. The phenotype of end-organ diseases is determined by the balance between metabo-inflammatory signals and homeostatic restorative factors. Some of the key end-organ diseases associated with obesity and metabo-inflammation include atherosclerotic vascular disease, hypertension, type 2 diabetes mellitus, chronic kidney disease and heart failure with preserved ejection fraction. Metabolic dysfunction-associated steatotic liver disease and steatohepatitis have recently been recognised as a part of a cluster of non-communicable diseases that account for the majority of premature deaths worldwide. The epidemiology, biological relationships of obesity to MASLD, mechanistic relationships between MASLD and other non-communicable diseases, and the clinical impact on patients are reviewed in this manuscript. We also include a basis for obesity-oriented treatment to manage MASLD. In summary, we provide a rationale for a holistic approach to the care of individuals with MASLD with a focus on treating obesity as a root cause, while monitoring liver status to determine the need for additional liver-targeted therapeutics.