Short-Term Energy Deprivation Alters Activin A and Follistatin But Not Inhibin B Levels of Lean Healthy Women in a Leptin-Independent Manner
ABSTRACT Leptin is a potent modulator of the hypothalamic-pituitary-gonadal axis mediating the effect of energy deprivation on several hypothalamic-pituitary-peripheral axes. Activin A, inhibin B, and follistatin (FST) also regulate the hypothalamic-pituitary-gonadal axis in humans. It remains unknown whether energy deprivation affects these hormone levels in a leptin-dependent or -independent manner.
We investigated 1) day-night variability patterns of activin, inhibin, and FST in the fed state, 2) whether their levels are affected by fasting, and 3) whether such an effect is mediated by leptin in physiological replacement or pharmacological doses.
We conducted two studies in healthy, eumenorrheic females, each comprising three separate admissions. In study 1, six women were maintained for 72 h 1) on isocaloric diet, 2) fasting while receiving placebo, or 3) fasting while receiving metreleptin in physiological replacement doses. In study 2, five women were administered physiological or pharmacological metreleptin doses (0.01, 0.1, or 0.3 mg/kg i.v. four times daily).
Neither activin A nor FST had a pulsatile or day-night variability pattern. Inhibin B levels were also nonpulsatile, but a trend toward a day-night pattern was noted. When compared with the fed state, inhibin B levels remained unchanged, whereas FST levels increased (P = 0.01) and activin A decreased (P = 0.01) in the fasting state. These changes were not corrected with metreleptin administered in replacement or pharmacological doses.
Short-term energy deprivation alters levels of activin A and FST, but these effects are not mediated by leptin.
- SourceAvailable from: Vassilis Mougios
[Show abstract] [Hide abstract]
- "Weight loss interventional study: Leptin and adiponectin levels were measured using RIA . Serum insulin and cortisol levels were measured with Siemens Immulite 1000  "
ABSTRACT: In mouse, PGC1-α overexpression in muscle stimulates an increase in expression of FNDC5, a membrane protein that is cleaved and secreted as a newly identified hormone, irisin. One prior study has shown that FNDC5 induces browning of subcutaneous fat in mice and mediates beneficial effects of exercise on metabolism, but a more recent study using gene expression arrays failed to detect a robust increase in FNDC5 mRNA in human muscles from exercising subjects. No prior study has reported on the physiological regulation and role of circulating irisin and FNDC5 in humans.Metabolism: clinical and experimental 09/2012; 61(12). DOI:10.1016/j.metabol.2012.09.002 · 3.61 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Objective Follistatin-like 3 (fstl3), a natural inhibitor of members of the TGF-β family, increases during resistance training in human plasma. Fstl3 primarily binds myostatin and activin A, and thereby inhibits their functions. We hypothesize that blocking myostatin and activin A signalling through systemic fstl3 over-expression protects against diet-induced obesity and insulin resistance. Methods Fstl3 was over-expressed by DNA electrotransfer in tibialis anterior, quadriceps and gastrocnemius muscles in female C57BL/C mice, and the mice were subsequently randomized to chow or high-fat feeding. Body weight, food intake, fat accumulation by MR scanning, and glucose, insulin and glucagon tolerance were evaluated, as was the response in body weight and metabolic parameters to 24 hours fasting. Effects of fstl3 on pancreatic insulin and glucagon content, and pancreatic islet morphology were determined. Results Fstl3 over-expression reduced fat accumulation during high-fat feeding by 16%, and liver fat by 50%, as determined by MRI. No changes in body weight were observed, while the weight of the transfected muscles increased by 10%. No transcriptional changes were found in the subcutaneous adipose tissue. Fstl3 mice displayed improved insulin sensitivity and muscle insulin signalling. In contrast, glucose tolerance was impaired in high-fat fed fstl3 mice, which was explained by increased hepatic glucagon sensitivity and glucose output, as well as a decrease in the pancreatic insulin/glucagon ratio. Accordingly, fstl3 transfection improved counter-regulation to 24 hours fasting. Conclusion Fstl3 over-expression regulates insulin and glucagon sensitivities through increased muscular insulin action, as well as increased hepatic glucagon sensitivity and pancreatic glucagon content.Metabolism 10/2014; 64(2). DOI:10.1016/j.metabol.2014.10.007 · 3.61 Impact Factor