Clinical features and metabolic complications for non-alcoholic fatty liver disease (NAFLD) in youth with obesity

Abstract

Pediatric obesity has become in the last forty years the most common metabolic disease in children and adolescents affecting about 25% of the pediatric population in the western world. As obesity worsens, a whole-body insulin resistance (IR) occurs. This phenomenon is more pronounced during adolescence, when youth experience a high degree of insulin resistance due the production of growth hormone. As IR progresses, the blunted control of insulin on adipose tissue lipolysis causes an increased flux of fatty acids with FFA deposition in ectopic tissues and organs such as the liver, leading to the development of NAFLD. In this brief review, we will discuss the clinical implications of IR and NAFLD in the context of pediatric obesity. We will review the pathogenesis and the link between these two entities, the major pathophysiologic underpinnings, including the role of genetics and metagenomics, how these two entities lead to the development of type 2 diabetes, and which are the therapeutic options for NAFLD in youth.

Clinical review: Guide to pharmacological management in pediatric obesity medicine

“…Nonalcoholic fatty liver disease (NAFLD; defined as fat accumulation in >5% of hepatocytes) encompasses a spectrum of liver disease which includes nonalcoholic hepatic steatosis, nonalcoholic steatohepatitis, cirrhosis, and liver failure [ 68 ]. Insulin resistance is exacerbated by hepatic fat accumulation and can promote free fatty acid accumulation in the liver [ 69 ].…”

Waistline to thigh circumference ratio as a predictor of MAFLD: a health care worker study with 2-year follow-up

“…In Chinese health care workers, MAFLD has also reached epidemic proportions, occurring in 37.4% of workers [ 4 ]. NAFLD, which includes a variety of clinicopathological entities, hepatic steatosis, hepatic steatohepatitis and hepatocellular carcinoma [ 5 , 6 ], is believed to be a manifestation of metabolic syndrome in the liver [ 7 ]. MAFLD is often associated with obesity, insulin resistance, dyslipidaemia, and hypertension [ 6 , 8 ].…”

“…NAFLD, which includes a variety of clinicopathological entities, hepatic steatosis, hepatic steatohepatitis and hepatocellular carcinoma [ 5 , 6 ], is believed to be a manifestation of metabolic syndrome in the liver [ 7 ]. MAFLD is often associated with obesity, insulin resistance, dyslipidaemia, and hypertension [ 6 , 8 ]. MAFLD is diagnosed through ultrasound, which is the most common diagnostic method for MAFLD in clinical practice.…”

Modelling and assessment of glucose‐lactate kinetics in youth with overweight, obesity and metabolic dysfunction‐associated steatotic liver disease: A pilot study

“…2,4 MASLD progression exacerbates overall insulin resistance, leading to cardiometabolic complications. [7][8][9] To understand how changes in glucose metabolism affect the development of complications of obesity in youth, we have recently developed a mathematical model for assessing in vivo glucose-lactate metabolism during an oral glucose tolerance test (OGTT). 3 As the model was originally developed using data from 3-h OGTT, in the present study we assessed (a) whether a 3-h OGTT protocol is as effective as a longer 4-h OGTT protocol to estimate OMM and lactate parameters, and (b) determine the relationship between glucose and lactate kinetics.…”

“…In obesity and insulin resistance states, augmented free fatty acid flux from adipose tissue and enhanced DNL driven by insulin resistance, induce hepatic fat accumulation, a key feature of metabolic dysfunction‐associated steatotic liver disease (MASLD) 2,4 . MASLD progression exacerbates overall insulin resistance, leading to cardiometabolic complications 7–9 …”