Fibroblast growth factor 23 levels decline following sleeve gastrectomy

Abstract

The bone-derived protein fibroblast growth factor 23 (FGF23) is a key regulator of phosphate and vitamin D homeostasis. A number of pieces of evidence link both circulating phosphate and FGF23 concentrations with measures of adiposity, cardiovascular risk and mortality. 1-7 Our group 8 and others 1-3 have demonstrated positive associations between circulating FGF23 and body mass index (BMI), fat mass and abdominal circumference in cross-sectional human studies. Furthermore, positive associations between FGF23 concentrations Abstract Objective: Levels of fibroblast growth factor 23 (FGF23) have been positively associated with measures of adiposity, cardiovascular disease and mortality. It is unclear whether the relationship of FGF23 with cardiovascular disease and mortality is confounded by obesity. We aimed to determine whether FGF23 concentrations decline following a reduction in adiposity after sleeve gastrectomy (SG). Design:The effect of SG on FGF23 was evaluated in 22 obese adults (59% male) with type 2 diabetes. Fat mass, weight, BMI, plasma intact FGF23, parathyroid hormone (PTH) and leptin were determined at baseline and at 12 months following SG.Results: At baseline, median (IQR) age was 51 (43-54) years, fat mass 47.8 (41.0-59.4) kg, BMI 40.9 (36.9-46.9) kg/m 2 and FGF23 66.2 (55.3-82.9) pg/mL.Significant changes in median BMI (−10.8 kg/m 2 , 95% CI: −12.9 to −7.2, P < 0.0001), fat mass (−20.0 kg, 95% CI: −26.7 to −12.4, P < 0.0001) and weight (−34.7 kg, 95% CI −40.0 to −23.1, P < 0.0001) were observed after SG. FGF23 (−12.4 pg/mL, 95% CI: −19.5 to 2.0, P = 0.005), PTH (−1.1 pmol/L, 95% CI: −1.7 to 0.2, P = 0.009) and leptin (−1687 pg/mL, 95% CI −4524 to −563, P = 0.01) declined following SG. Change in FGF23 was not significantly associated with change in measures of adiposity, PTH or leptin.Conclusions: FGF23 concentrations decline in the setting of significant weight loss following SG, implying that increased FGF23 concentrations are a downstream consequence of obesity, which may confound its association with cardiometabolic dysfunction. Mediators of the relationship between adiposity and FGF23 require further elucidation. K E Y W O R D Sadiposity, bariatric surgery, bone mineral density, fibroblast growth factor 23, leptin, obesity, parathyroid hormone

Clinical improvement may not reflect metabolic homeostasis normalization in subjects with and without Roux-En-Y bariatric surgery after 12 years: comparison of surgical subjects to a lean cohort

“…Normalization of adiponectin in animal models has been associated with preventing cardiac dysfunction ( 35 ) indicating the importance of its restoration to non-obese levels. Adipsin, the other adipokine measured, was higher in the non-surgical comparator-subjects-with-obesity compared to normal-weight subjects though was no different to the surgical patients; adipsin was not shown to change after weight loss following sleeve gastrectomy ( 36 ) indicating that weight loss, but not to normal weight, was ineffective for modulation of this adipokine, as is confirmed here.FGF23 levels were significantly lower in normal-weight subjects compared to surgery and the non-surgical comparator-subjects-with-obesity, an observation that has been reported following sleeve gastrectomy ( 30 ). Whilst FGF23 is recognized to decrease after surgery ( 30 ), that fall was not compared to a normal population and therefore a novel finding of this study is that the fall reported here is not to the level found in subjects with a normal BMI.…”

“…Adipsin, the other adipokine measured, was higher in the non-surgical comparator-subjects-with-obesity compared to normal-weight subjects though was no different to the surgical patients; adipsin was not shown to change after weight loss following sleeve gastrectomy ( 36 ) indicating that weight loss, but not to normal weight, was ineffective for modulation of this adipokine, as is confirmed here.FGF23 levels were significantly lower in normal-weight subjects compared to surgery and the non-surgical comparator-subjects-with-obesity, an observation that has been reported following sleeve gastrectomy ( 30 ). Whilst FGF23 is recognized to decrease after surgery ( 30 ), that fall was not compared to a normal population and therefore a novel finding of this study is that the fall reported here is not to the level found in subjects with a normal BMI. This is perhaps not surprising as FGF23 has been associated with insulin resistance and inflammation ( 12 ) and, whilst there was a marked decrease in body weight after surgery that would be associated with a reduction in both insulin resistance and inflammation, these patients still had a significant weight difference compared to normal-weight subjects.…”

Caloric Intake in Renal Patients: Repercussions on Mineral Metabolism

“…Thus, regulation of renal α-klotho by caloric intake could influence FGF23 synthesis and secretion. Studies in humans also support the role of reducing caloric intake on FGF23, e.g., a decrease in circulating FGF23 concentrations has been reported in patients subjected to bariatric surgery [52].…”

Lack of PTEN in osteocytes increases circulating phosphate concentrations by decreasing intact fibroblast growth factor 23 levels

“…PTH may also be a candidate factor for this connection because PTH levels are elevated in obese subjects 28 , 29 and there is evidence to show that PTH is a positive regulator for FGF23 12 , 13 . However, Billington et al recently reported that FGF23 concentrations decreased after sleeve gastrectomy independent of changes in adiposity, PTH, and leptin levels 30 , which suggests an additional factor affecting FGF23 concentrations in humans. Based on accumulating evidence showing a relationship between insulin and FGF23 levels in humans 17 , 18 , insulin signaling has been implicated in the regulation of FGF23.…”