Angiopoietin-like 8 (ANGPTL8) as a potential predictor of NAFLD in paediatric patients with Prader-Willi Syndrome

Mele, Chiara; Crinò, Antonino; Fintini, Danilo; Mai, Stefania; Convertino, Alessio; Bocchini, Sarah; Paolo, Pierluigi Di; Grugni, Graziano; Aimaretti, Gianluca; Scacchi, Massimo; Marzullo, Paolo

doi:10.1007/s40618-020-01444-w

Cited by 4 publications

(3 citation statements)

References 52 publications

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“…Human and animal research and meta-analyses indicated that ANGPTL-8 is elevated in patients with NAFLD and can be used as a marker for NAFLD patients. Elevated levels of ANGPTL-8 were also correlated with the severity of NAFLD ( 20 , 21 , 50 ). Alternatively, some also hypothesized that the rise in serum ANGPTL-8 level in metabolic illnesses might be a compensatory response to the increased insulin resistance ( 51 ).…”

Section: Discussionmentioning

confidence: 94%

Nonalcoholic Fatty Liver Disease, Liver Fibrosis, and Utility of Noninvasive Scores in Patients With Acromegaly

Eroğlu,

Iremli,

Idilman

et al. 2023

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context NAFLD is a metabolical disorder and can lead to liver fibrosis. Because it is commonly seen, several noninvasive scores (NS) have been validated to identify high-risk patients. Patients with NAFLD were shown to have higher serum ANGPTL-8 levels. Objective The risk of NAFLD is known insufficiently in acromegaly. Moreover, the utility of the NS and the link between NAFLD and ANGPTL-8 in acromegaly is unknown. Methods Thirty-two acromegalic patients(n = 15, active(AA) and n = 17, controlled acromegaly(CA)) and 19 healthy controls were included. MRI-proton density fat fraction(MRI-PDFF) was used to evaluate hepatic steatosis, and MR elastography(MRE) to evaluate liver stiffness measurement(LSM). ANGPTL-8 levels were measured with ELISA. Results Median liver MRI-PDFF and NAFLD prevalence in AA were lower than in CA(p = 0.026 and p < 0.001, respectively). Median MRE-LSM were similar across groups. Of the NS, VAI(visceral adiposity index), FLI(fatty liver index), HSI(hepatic steatosis index), and TyG(triglyceride-glucose index) all showed positive correlation with the liver MRI-PDFF in the control group. However, only TyG significantly correlated with liver fat in the AA and CA groups. There was no correlation between traditional NAFLD risk factors (BMI, waist circumference, CRP, HOMA-IR, visceral adipose tissue) and liver MRI-PDFF in the AA and CA. Acromegalic patients with NAFLD had lower GH, IGF-1, and ANGPTL-8 levels than in those without NAFLD(p = 0.025, p = 0.011, and p = 0.036, respectively). Conclusion Active acromegaly may protect from NAFLD due to high GH. In acromegalic patients, NAFLD risk cannot be explained with classical risk factors, hence additional risk factors must be identified. TyG is the best score to evaluate NAFLD risk. Lower ANGPTL-8 in acromegalic patients with NAFLD implies this hormone may be raised due to insulin resistance rather than being a cause for NAFLD.

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Section: Discussionmentioning

confidence: 94%

Nonalcoholic Fatty Liver Disease, Liver Fibrosis, and Utility of Noninvasive Scores in Patients With Acromegaly

Eroğlu,

Iremli,

Idilman

et al. 2023

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…Although this adverse phenotype, obese children and adolescents with PWS have a milder metabolic derangement compared to their BMI-matched controls ( 11 , 45 , 46 ). In particular, PWS children show lower insulin and C-peptide levels, lower insulin resistance, as well as higher adiponectin and HDL cholesterol levels ( 47 ). Our study confirmed these peculiarities: in patients with PWS, in fact, we found significantly lower fasting and post-OGTT insulin levels, C-peptide and HOMA-IR together with higher levels of adiponectin with respect to controls matched for BMI SDS, confirming better insulin sensitivity.…”

Section: Discussionmentioning

confidence: 99%

Circulating Irisin in Children and Adolescents With Prader-Willi Syndrome: Relation With Glucose Metabolism

Mai

Fintini²,

Mele³

et al. 2022

Front. Endocrinol.

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Irisin is a myokine involved in the browning of white adipose tissue and regulation of energy expenditure, glucose homeostasis and insulin sensitivity. Debated evidence exists on the metabolic role played by irisin in children with overweight or obesity, while few information exist in children with Prader Willi Syndrome (PWS), a condition genetically prone to obesity. Here we assessed serum irisin in relation to the metabolic profile and body composition in children and adolescents with and without PWS. In 25 PWS subjects [age 6.6-17.8y; body mass index standard deviation score (BMI SDS) 2.5 ± 0.3] and 25 age, and BMI-matched controls (age 6.8-18.0y; BMI SDS, 2.8 ± 0.1) we assessed irisin levels and metabolic profile inclusive of oral glucose tolerance test (OGTT), and body composition by dual-energy X-ray absorptiometry (DXA). In PWS, we recorded lower levels of fat-free mass (FFM) (p <0.05), fasting (p<0.0001) and 2h post-OGTT insulin (p<0.05) and lower insulin resistance as expressed by homeostatic model of insulin resistance (HOMA-IR) (p<0.0001). Irisin levels were significantly lower in PWS group than in controls with common obesity (p<0.05). In univariate correlation analysis, positive associations linked irisin to insulin OGTT0 (p<0.05), insulin OGTT120 (p<0.005), HOMA-IR (p<0.05) and fasting C-peptide (p<0.05). In stepwise multivariable regression analysis, irisin levels were independently predicted by insulin OGTT120. These results suggest a link between irisin levels and insulin sensitivity in two divergent models of obesity.

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“…Meanwhile, it also associated with the development of NAFLD ( 15 , 49 ). Previous study proved that ANGPTL8 is able to reduce serum triglyceride clearance through the inhibition of lipoprotein lipase(LPL), which hydrolyzes triglycerides, therefore, increased ANGPTL8 leads to triglycerides accumulation ( 50 , 51 ). On the other hand, the mechanism of association between NAFLD development and resistin elevation is also unclear.…”

Section: Discussionmentioning

confidence: 99%

Association of ANGPTL8 and Resistin With Diabetic Nephropathy in Type 2 Diabetes Mellitus

Fan

Peng

et al. 2021

Front. Endocrinol.

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BackgroundPrevious studies showed altered angiopoietin-like protein-8 (ANGPTL-8) and resistin circulating levels in type 2 diabetes mellitus (T2DM). Whether or not the alteration in ANGPTL-8 and resistin level can be a predictive maker for increased diabetic nephropathy risk remains unclear.AimTo Investigate the possible association of ANGPTL-8 and resistin with DN, and whether this association is affected by NAFLD status.MethodsA total of 278 T2DM patients were enrolled. Serum levels of ANGPTL8, resistin, BMI, blood pressure, duration of diabetes, glycosylated hemoglobin (HbA1c), fasting blood glucose (FPG), hypersensitive C-reactive protein (hs-CRP), lipid profile, liver, and kidney function tests were assessed. The relationship between DN with ANGPTL8 and resistin was analyzed in the unadjusted and multiple-adjusted regression models.ResultsSerum levels of ANGPTL8 and resistin were significantly higher in DN compared with T2DM subjects without DN (respectively; P <0.001), especially in non-NAFLD populations. ANGPTL8 and resistin showed positive correlation with hs-CRP (respectively; P<0.01), and negative correlation with estimated GFR (eGFR) (respectively; P=<0.001) but no significant correlation to HOMA-IR(respectively; P>0.05). Analysis showed ANGPTL8 levels were positively associated with resistin but only in T2DM patients with DN(r=0.1867; P<0.05), and this significant correlation disappeared in T2DM patients without DN. After adjusting for confounding factors, both ANGPTL8(OR=2.095, 95%CI 1.253-3.502 P=0.005) and resistin (OR=2.499, 95%CI 1.484-4.208 P=0.001) were risk factors for DN. Data in non-NAFLD population increased the relationship between ANGPTL8 (OR=2.713, 95% CI 1.494-4.926 P=0.001), resistin (OR=4.248, 95% CI 2.260-7.987 P<0.001)and DN. The area under the curve (AUC) on receiver operating characteristic (ROC) analysis of the combination of ANGPTL8 and resistin was 0.703, and the specificity was 70.4%. These data were also increased in non-NAFLD population, as the AUC (95%CI) was 0.756, and the specificity was 91.2%.ConclusionThis study highlights a close association between ANGPTL8, resistin and DN, especially in non-NAFLD populations. These results suggest that ANGPTL-8 and resistin may be risk predictors of DN.

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Angiopoietin-like 8 (ANGPTL8) as a potential predictor of NAFLD in paediatric patients with Prader-Willi Syndrome

Cited by 4 publications

References 52 publications

Nonalcoholic Fatty Liver Disease, Liver Fibrosis, and Utility of Noninvasive Scores in Patients With Acromegaly

Nonalcoholic Fatty Liver Disease, Liver Fibrosis, and Utility of Noninvasive Scores in Patients With Acromegaly

Circulating Irisin in Children and Adolescents With Prader-Willi Syndrome: Relation With Glucose Metabolism

Association of ANGPTL8 and Resistin With Diabetic Nephropathy in Type 2 Diabetes Mellitus

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