NAFLD as a continuum: from obesity to metabolic syndrome and diabetes

Abstract

Background: The prevalence of non-alcoholic fatty liver disease (NAFLD) has been increasing rapidly. It is nowadays recognized as the most frequent liver disease, affecting a quarter of global population and regularly coexisting with metabolic disorders such as type 2 diabetes, hypertension, obesity, and cardiovascular disease. In a more simplistic view, NAFLD could be defined as an increase in liver fat content, in the absence of secondary cause of steatosis. In fact, the clinical onset of the disease is a much more complex process, closely related to insulin resistance, limited expandability and dysfunctionality of adipose tissue. A fatty liver is a main driver for a new recognized liver-pancreatic α-cell axis and increased glucagon, contributing to diabetes pathophysiology. Main text: This review will focus on the clinical and pathophysiological connections between NAFLD, insulin resistance and type 2 diabetes. We reviewed non-invasive methods and several scoring systems for estimative of steatosis and fibrosis, proposing a multistep process for NAFLD evaluation. We will also discuss treatment options with a more comprehensive view, focusing on the current available therapies for obesity and/or type 2 diabetes that impact each stage of NAFLD. Conclusion: The proper understanding of NAFLD spectrum-as a continuum from obesity to metabolic syndrome and diabetes-may contribute to the early identification and for establishment of targeted treatment.

New Perspectives on Genetic Prediction for Pediatric Metabolic Associated Fatty Liver Disease

“…Due to a continuum from obesity to metabolic syndrome, patients with MAFLD may benefit from early identification of the disease risk and individually targeted treatment ( 13 ). Establishing clinical predictors is necessary for MAFLD diagnosis and risk stratification.…”

A CD209 ligand and a sialidase inhibitor differentially modulate adipose tissue and liver macrophage populations and steatosis in mice on the Methionine and Choline-Deficient (MCD) diet

“…In addition, increased numbers of adipose tissue and liver macrophages appears to correlate with progression from simple steatosis to NASH and fibrosis [ 22 , 23 ]. This suggest that adipose tissue dysfunction is important in the generation of steatosis and liver inflammation in patients with NASH [ 21 , 24 ]. Although many factors have been shown to be involved in NAFLD and NASH, how these molecules modulate inflammation and what is the role of the tissue resident liver macrophages (Kupffer cells) and recruited immune cells in driving or inhibiting NASH are yet to be clarified [ 25 , 26 ].…”

Beneficial effect of omarigliptin on diabetic patients with non-alcoholic fatty liver disease/non-alcoholic steatohepatitis

“…Accordingly, excess DPP4 derived from adipocytes and/or hepatocytes may act as a local mediator of in ammation and adipose/hepatic tissue insulin resistance, thereby forming a link between obesity and the pathogenesis of tpe2 diabetes and metabolic disease. Sodium-glucose transporter 2 inhibitors and glucagon-like peptide 1 receptor agonists have recently shown potential e cacy for the treatment of NAFLD/NASH with diabetes [1,15,16], but are expected to be more effective for NAFLD/NASH in obese diabetic patients. The effects of OMG in decreasing intrahepatic fat accumulation and improving intrahepatic adipose in ammation are expected to be helpful for the treatment of NAFLD/NASH, particularly in non-obese, insulin-resistant, diabetic patients.…”

“…Dipeptidyl peptidase 4 (DPP4) is a serine exopeptidase able to inactivate various oligopeptides through the removal of N-terminal dipeptides [1]. The activity of DPP4 seems to be increased in patients with type 2 diabetes, and various in vitro and in vivo studies have demonstrated that this enzyme can interact with proin ammatory pathways [1].…”

“…Dipeptidyl peptidase 4 (DPP4) is a serine exopeptidase able to inactivate various oligopeptides through the removal of N-terminal dipeptides [1]. The activity of DPP4 seems to be increased in patients with type 2 diabetes, and various in vitro and in vivo studies have demonstrated that this enzyme can interact with proin ammatory pathways [1]. DPP4 is also a hepatokine [2], and levels of this enzyme have thus been seen to be elevated in chronic liver diseases including hepatitis C, hepatitis B, non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma.…”