Lipid metabolic reprogramming mediated by circulating Nrg4 alleviates metabolic dysfunction-associated steatotic liver disease

1. In patients with obesity who had previously undergone a sleeve gastrectomy and are in the early phases of recovery, circulating levels of adipokines, particularly Nrg4, help alleviate hepatic steatosis resulting from metabolic dysfunction-associated steatotic liver disease (MASLD). 

Evidence Rating Level: 3 (Average) 

One challenge facing health care systems is metabolic dysfunction-associated steatotic liver disease (MASLD). Metabolic and bariatric surgery (MBS) remains an effective mechanism to help MASLD as it has weight-loss dependent and independent positive effects with multiple organs benefiting from the metabolic reprogramming it provides. Adipokines have been a popular choice for diet-induced hepatic steatosis, resulting from their potential for diagnosis and treatment. As a result, this case-control study was created to evaluate the effects of the three most commonly used adipokines (Nrg4, leptin, and adiponectin) during the early recovery phase after a sleeve gastrectomy (SG). To assess the effects of the medications, individuals with MASLD, a BMI ≥ 30 kg/m2, and who underwent laparoscopic SG were recruited in Shanghai. As this is a case-control study, individuals without an obese BMI and MASLD were recruited as the controls. An enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of rg4, leptin, and adiponectin. Before the cases had SG, they had hepatic steatosis (p<0.001), hepatic dysfunction (i.e. ALT, AST, GGT; all p values < 0.001), dyslipidemia (i.e. TC, TG, HDL-c, LDL-c; all p values < 0.01 except TC), and dysglycemia (i.e. fasting glucose, fasting insulin, HOMA-IR; all p values ≤0.001). After surgery, the liver/spleen CT value ratio (LSR) increased (p=0.011) while there were no significant improvements in liver function indicators such as ALT (p=1.000), AST (p=0.299) or GGT (p=0.08). On the other hand, lipid and glucose metabolism levels decreased (i.e. TC, p=0.002; TG, p=0.032; fasting glucose, p=0.009; fasting insulin, p=0.036; HOMA-IR, p=0.013). In all, treatment with Nrg4 alleviated symptoms of MASLD. 

Click to read the study in BMC Medicine

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