Circulating angiopoietin-like 8 (ANGPTL8) is a marker of liver steatosis and is negatively regulated by Prader-Willi Syndrome

Abstract

ANGPTL8 is a liver-derived protein related to insulin-sensitivity. Its relationship with obesity and liver function in Prader-Willi syndrome (PWS) is unknown. The present study investigated circulating ANGPTL8 in PWS and controls with common obesity, assessing its association to liver steatosis. For this purpose, 20 obese PWS and 20 controls matched for body mass index (BMI), sex and age underwent analysis of ANGPTL8 levels, glucose and lipid metabolism. Liver function tests and degree of liver steatosis by ultrasonography (US), fat-free mass (FFM) and fat mass (FM) by dual-energy x-ray absorptiometry (DEXA) were also assessed. In comparison to controls, obese PWS showed lower values of FFM (p < 0.0001) and higher FM (p = 0.01), while harbouring higher HDL cholesterol, lower triglycerides and OGTT-derived insulin levels, as well as a lower prevalence and severity of liver steatosis. With respect to obese controls, ANGPTL8 levels were significantly lower in PWS (p = 0.007) and overall correlated with transaminase levels and the severity of liver steatosis, as well as FFM (p < 0.05 for all). By a stepwise multivariable regression analysis, ANGPTL8 levels were independently predicted by PWS status (p = 0.01) and liver steatosis (p < 0.05). In conclusion, ANGPTL8 levels are lower in PWS than obese controls and are inversely associated with the severity of liver steatosis. Further studies should investigate the potential genetic basis for this observation.

Association between circulating full-length angiopoietin-like protein 8 and non-high-density lipoprotein cholesterol levels in Chinese non-diabetic individuals: a cross-sectional study

“…It is possible that the inconsistency may be associated with the origins of obesity. It is reported that circulating ANGPTL8 concentrations are different in people with obesity depending on the origins of obesity [ 46 ] which may be linked to body composition, basal metabolic rate, or metabolic outcomes [ 47 ]. To avoid a confounding effect, we adjusted for age and BMI in this study.…”

“…To avoid a confounding effect, we adjusted for age and BMI in this study. Circulating ANGPTL8 concentrations are elevated in patients with non-alcoholic fatty liver disease [ 48 ] and liver steatosis [ 46 ]. It is also reported that there is a positive association between circulating ANGPTL8 and serum Hs-CRP [ 11 ].…”

Irisin levels in genetic and essential obesity: clues for a potential dual role

“…Body measurements. All subjects underwent body measurements wearing light underwear, in fasting conditions after voiding as described previously 25,26 . Weight and height were measured to the nearest 0.1 kg and 0.1 cm, respectively, using standard methods.…”

“…Waist circumference (WC) was measured midway between the lowest rib and the top of the iliac crest after gentle expiration; hip measurements were taken at the greatest circumference around the nates. FM and FFM were determined by bioelectrical impedance analysis (BIA model 101/S Akern, Florence, Italy) as described previously 26 . According to the vectorial analysis, patients with fluid overload were excluded to minimize errors in estimating FM and FFM.…”

Paediatric fatty liver disease (PeFLD): All is not NAFLD – Pathophysiological insights and approach to management

“…124 Prader-Willi syndrome patients exhibit unique body composition in comparison to obese controls 125,122 with higher insulin sensitivity alluding to alternative pathogenic pathways. 126,127 Wilson's disease A wide spectrum of histological findings can be found in Wilson's disease, ranging from a chronic porto-lobular hepatitis with no steatosis to a steatohepatitis-like picture, similar to that seen in alcoholic liver disease. Special stains for copper may help point towards the diagnosis, but the distribution of copper may be patchy and not always be present.…”