Key result
Changes in circulating ANGPTL3 levels during an 8-week low-calorie diet were strongly positively associated with changes in the liver apoptosis marker cytokeratin 18 (β 0.21).
Why the study?
Are changes in circulating ANGPTL3 levels during an 8-week low-calorie diet associated with liver markers and genetic variants in obese individuals?
Observational (n=769)
Yes
Are changes in circulating ANGPTL3 levels during an 8-week low-calorie diet associated with liver markers and genetic variants in obese individuals?
Effect estimate: β 0.21 (95% CI 0.15-0.26)
p-value: p=1.47 × 10−13
Circulating ANGPTL3 levels and their changes during weight loss are strongly associated with markers of liver apoptosis and inflammation (CK-18, AST) and are modulated by trans-acting genetic variants.
ANGPTL3 changes during weight loss track liver apoptosis; hypothesis-generating for therapeutic targeting but should not yet change practice.
Angiopoietin-like protein 3 (ANGPTL3), a liver-derived protein, plays an important role in the lipid and lipoprotein metabolism. Using data available from the DiOGenes study, we assessed the link with clinical improvements (weight, plasma lipid, and insulin levels) and changes in liver markers, alanine aminotransferase, aspartate aminotransferase (AST), adiponectin, fetuin A and B, and cytokeratin 18 (CK-18), upon low-calorie diet (LCD) intervention. We also examined the role of genetic variation in determining the level of circulating ANGPTL3 and the relation between the identified genetic markers and markers of hepatic steatosis. DiOGenes is a multicenter, controlled dietary intervention where obese participants followed an 8-week LCD (800 kcal/day, using a meal replacement product). Plasma ANGPTL3 and liver markers were measured using the SomaLogic (Boulder, CO) platform. Protein quantitative trait locus (pQTL) analyses assessed the link between more than four million common variants and the level of circulating ANGPTL3 at baseline and changes in levels during the LCD intervention. Changes in ANGPTL3 during weight loss showed only marginal association with changes in triglycerides (nominal p = 0.02) and insulin ( p = 0.04); these results did not remain significant after correcting for multiple testing. However, significant association (after multiple-testing correction) were observed between changes in ANGPTL3 and AST during weight loss ( p = 0.004) and between ANGPTL3 and CK-18 (baseline p = 1.03 × 10 −7 , during weight loss p = 1.47 × 10 −13 ). Our pQTL study identified two loci significantly associated with changes in ANGPTL3. One of these loci (the APOA4 - APOA5-ZNF259 - BUD13 gene cluster) also displayed significant association with changes in CK-18 levels during weight loss ( p = 0.007). We clarify the link between circulating levels of ANGPTL3 and specific markers of liver function. We demonstrate that changes in ANGPLT3 and CK-18 during LCD are under genetic control from trans -acting variants. Our results suggest an extended function of ANGPTL3 in the inflammatory state of liver steatosis and toward liver metabolic processes.
No takes yet. Share an insight, caveat, or question.
Hess et al. (2018) conducted an observational in Overweight and obesity (n=769). Circulating ANGPTL3 levels was evaluated on Association between changes in circulating ANGPTL3 and cytokeratin 18 (CK-18) during weight loss (β 0.21, 95% CI 0.15-0.26, p=1.47 × 10−13). Changes in circulating ANGPTL3 levels during an 8-week low-calorie diet were strongly positively associated with changes in the liver apoptosis marker cytokeratin 18 (β 0.21).