Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as the most common liver disease worldwide in recent years. MASLD commonly presents as simple hepatic steatosis, but ~25% of patients develop liver inflammation, progressive fibrosis, liver cirrhosis and related hepatocellular carcinoma. Liver inflammation and the degree of fibrosis are key determinants of the prognosis. The pathophysiology of liver inflammation is incompletely understood and involves diverse factors and specifically innate and adaptive immune responses. More specifically, diverse mediators of innate immunity such as proinflammatory cytokines, adipokines, inflammasomes and various cell types like mononuclear cells, macrophages and natural killer cells are involved in directing the inflammatory process in MASLD. The activation of innate immunity is driven by various factors including excess lipids and lipotoxicity, insulin resistance and molecular patterns derived from gut commensals. Targeting pathways of innate immunity might therefore appear as an attractive therapeutic strategy in the future management of MASLD and possibly its complications.

The incidence and prevalence of obesity and related cardio-metabolic diseases are on the rise, posing a critical health care challenge to systems across the globe. Bariatric surgery is a therapeutic cornerstone for morbidly obese patients, besides novel medical treatments, partly by ameliorating metabolic inflammation, a hallmark of metabolic diseases. Acyl-CoA Binding Protein (ACBP), also known as diazepam-binding inhibitor (DBI), is a regulator of autophagy and metabolism, and has recently been shown to increase in individuals undergoing voluntary fasting and in patients with cancer cachexia-induced malnutrition. By analyzing a prospectively collected study with matched serum and liver samples from patients undergoing laparoscopic adjustable gastric banding at baseline and six months after surgery, we here demonstrate that ACBP serum levels significantly increase following bariatric surgery. Hepatic ACBP expression at baseline predicted weight loss six months after the procedure. The predictive value of ACBP warrants further study, as it could identify patients who benefit most from metabolic surgery in the future.