Publications

Authors:

Maffeis, Claudio; Morandi, Anita; Zusi, Chiara; Olivieri, Francesca; Fornari, Elena; Cavarzere, Paolo; Piona, Claudia; Corradi, Massimiliano; Emiliani, Federica; Da Ros, Alessandro; Berni Canani, Roberto; Mantovani, Alessandro; Targher, Giovanni

Title:

Hepatic lipogenesis marked by GCKR-modulated triglycerides increases serum FGF21 in children/teens with obesity

Year:

2025

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Referee:

No

Name of journal:

DIABETES, OBESITY AND METABOLISM

ISSN of journal:

1462-8902

N° Volume:

27

Number or Folder:

2

Page numbers:

825-834

Keyword:

insulin resistance; lipid‐lowering therapy; MASLD; obesity care

Short description of contents:

Aims Fibroblast growth factor 21 (FGF21) decreases hepatic lipogenesis in animal models, and FGF21 analogues decrease serum triglycerides (TG) in adults in phase-2 trials. On the other hand, serum FGF21 is associated with higher TG in observational studies of people with obesity, raising a sort of paradox. We tested the hypothesis that FGF21 is induced by TG in youth with obesity, as a compensatory mechanism. Materials and Methods We recruited 159 children/adolescents with obesity (80 males, 12.7 +/- 2.1 years). Besides serum FGF21 and lipid dosages, we genotyped the Pro446Leu variant at glucokinase regulator (GCKR) as a known marker of genetically increased hepatic de novo lipogenesis, and we used it as an instrumental variable to establish a cause-and-effect relationship between FGF21 and TG, according to a Mendelian randomization analysis. Results The Pro446Leu variant increased circulating TG (beta = +0.35, p < 0.001), which was positively associated with circulating FGF21 (beta = +0.42, p < 0.001). The Pro446Leu variant increased FGF-21 (beta = +0.14, p = 0.031) with the expected slope (beta-coefficient) in case of association entirely mediated by TG: 0.35 (slope between Pro446Ala and TG) x 0.42 (slope between TG and FGF21) = 0.14. Conclusions Hepatic lipogenesis, marked by GCKR-modulated triglycerides, is significantly associated with increased serum FGF-21 in children/adolescents with obesity.

Product ID:

144235

Handle IRIS:

11562/1153932

Last Modified:

February 8, 2025

Bibliographic citation:

Maffeis, Claudio; Morandi, Anita; Zusi, Chiara; Olivieri, Francesca; Fornari, Elena; Cavarzere, Paolo; Piona, Claudia; Corradi, Massimiliano; Emiliani, Federica; Da Ros, Alessandro; Berni Canani, Roberto; Mantovani, Alessandro; Targher, Giovanni, Hepatic lipogenesis marked by GCKR-modulated triglycerides increases serum FGF21 in children/teens with obesity «DIABETES, OBESITY AND METABOLISM» , vol. 27 , n. 2 , 2025 , pp. 825-834

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