Growth differentiation factor 15 increases in both cerebrospinal fluid and serum during pregnancy

Abstract

Aim Growth differentiation factor 15 (GDF15) increases in serum during pregnancy to levels not seen in any other physiological state and is suggested to be involved in pregnancy-induced nausea, weight regulation and glucose metabolism. The main action of GDF15 is regulated through a receptor of the brainstem, i.e., through exposure of GDF15 in both blood and cerebrospinal fluid (CSF). The aim of the current study was to measure GDF15 in both CSF and serum during pregnancy, and to compare it longitudinally to non-pregnant levels. Methods Women were sampled at elective caesarean section (n = 45, BMI = 28.1±5.0) and were followed up 5 years after pregnancy (n = 25). GDF15, insulin and leptin were measured in CSF and serum. Additional measurements included plasma glucose, and serum adiponectin and Hs-CRP. Results GDF15 levels were higher during pregnancy compared with follow-up in both CSF (385±128 vs. 115±32 ng/l, P<0.001) and serum (73789±29198 vs. 404±102 ng/l, P<0.001). CSF levels correlated with serum levels during pregnancy (P<0.001), but not in the non-pregnant state (P = 0.98). Both CSF and serum GDF15 were highest in women carrying a female fetus (P<0.001). Serum GDF15 correlated with the homeostatic model assessment for beta-cell function and placental weight, and CSF GDF15 correlated inversely with CSF insulin levels. Conclusion This, the first study to measure CSF GDF15 during pregnancy, demonstrated increased GDF15 levels in both serum and CSF during pregnancy. The results suggest that effects of GDF15 during pregnancy can be mediated by increases in both CSF and serum levels.

Growth Differentiation Factor‐15 Predicts Mortality and Heart Failure Exacerbation But Not Ventricular Arrhythmias in Patients With Cardiomyopathy

“…While further studies are needed for elucidating sexual differences in GDF‐15 expression, a female predominance in our HF group may have theoretically skewed our results. 29 , 30 …”

The Role of GDF15 as a Myomitokine

“…Circulating GDF15 increases with aging and today GDF15 is recognized as a reliable biomarker of aging [ 21 ], reaching levels of around 3–5 ng/mL in centenarians [ 22 ]. In line with its high expression in placenta, circulating GDF15 is very strongly increased during pregnancy, reaching levels as high as 60–70 ng/mL in the third trimester [ 23 ]. Furthermore, GDF15 is increased in a number of different pathologies and diseases (many of those age related) such as chronic inflammatory disease, cardiovascular and renal disease, as well as different malignancies.…”

Circulating Growth Differentiation Factor 15 and Preeclampsia: A Meta-Analysis

“…In addition, the production of GDF15 by adipocytes is also induced by oxidative stress, a well-known to cause preeclampsia [19]. In pregnant women, the circulating level of GDF-15 is shown to significantly increase to approximately a 15-fold of the non-pregnant women [20]. Moreover, variations of the circulating levels of GDF-15 have been noticed in women with miscarriage [21,22] and gestational diabetes mellitus [23].…”