Reduction in serum fibroblast growth factor-21 after gastric bypass is related to changes in hepatic fat content

Abstract

BackgroundFibroblast growth factor 21 (FGF21) is elevated in obesity. ObjectivesWe investigated the circulating level of FGF21 and the expression of FGF21, beta-klotho (KLB), and FGF receptor 1 (FGFR1) in adipose tissue in relation to weight, fat distribution, and Roux-en-Y gastric bypass (RYGB)-induced weight loss. SettingThe Department of Endocrinology at Aarhus University Hospital. MethodsThirty-one obese patients were enrolled. Visceral adipose tissue volume measured by magnetic resonance imaging, hepatic fat content measured by magnetic resonance spectroscopy, and body composition measured by dual-energy x-ray absorbtiometry were determined at baseline and 12 months after RYGB. Fasting blood samples and subcutaneous and visceral adipose tissue samples were obtained. Moreover, 25 lean controls were enrolled. ResultsFGF21 was significantly elevated in obese patients compared with lean patients (281±151 pg/mL versus 149±99 pg/mL, P<.05). RYGB-induced weight loss resulted in a smaller reduction in FGF21 (P = .08). However, a significant reduction was seen in obese patients with initially high FGF21 levels (42% reduction, P<.001). A significant association was found between FGF21 and hepatic fat content at baseline (r = 0.40, P<.05). Moreover, ΔFGF21 was significantly associated with Δhepatic fat content after RYGB (r = 0.39, P<.05). FGF21 mRNA was not detectable in AT from either lean or obese patients. KLB and FGFR1 were upregulated in AT in relation to obesity, and both were further increased 12 months after RYGB. ConclusionsFGF21 is reduced in relation to weight loss in patients with initial high levels of FGF21 and this reduction is significantly associated with a reduction in hepatic fat content. Thus, changes in FGF21 after RYGB-induced weight loss are closely related to changes in liver fat content.