Plasma brain-derived neurotrophic factor in women after bariatric surgery: a pilot study
2008; Elsevier BV; Volume: 91; Issue: 4 Linguagem: Inglês
10.1016/j.fertnstert.2008.09.032
ISSN1556-5653
AutoresZaher Merhi, Howard Minkoff, Geralyn Lambert‐Messerlian, Jerzy Macura, Joseph Feldman, David B. Seifer,
Tópico(s)Tissue Engineering and Regenerative Medicine
ResumoEighteen morbidly obese women had plasma brain-derived neurotrophic factor (BDNF) measured before bariatric surgery and 3 months postoperatively. We analyzed plasma BDNF levels in all the participants then subdivided according to menopausal status and type of surgery. Brain-derived neurotrophic factor decreased significantly in all the participants and in the premenopausal group when looked at in isolation. Eighteen morbidly obese women had plasma brain-derived neurotrophic factor (BDNF) measured before bariatric surgery and 3 months postoperatively. We analyzed plasma BDNF levels in all the participants then subdivided according to menopausal status and type of surgery. Brain-derived neurotrophic factor decreased significantly in all the participants and in the premenopausal group when looked at in isolation. Obesity is one of the fastest-growing health problems in the United States (1Christakis N.A. Fowler J.H. The spread of obesity in a large social network over 32 years.N Engl J Med. 2007; 357: 370-379Crossref PubMed Scopus (3333) Google Scholar). Bariatric surgery can lead to substantial weight reduction. Both the estimated number of bariatric surgical procedures and the number of practicing bariatric surgeons have increased markedly in the United States (2Santry H.P. Gillen D.L. Lauderdale D.S. Trends in bariatric surgical procedures.JAMA. 2005; 294: 1909-1917Crossref PubMed Scopus (772) Google Scholar).Brain-derived neurotrophic factor (BDNF), a protein that belongs to the neurotrophin family and originally described in the nervous system, has been shown to be expressed in nonneuronal tissues like the ovaries, and to be present in plasma (3Yamamoto M. Sobue G. Yamamoto K. Terao S. Mitsuma T. Expression of mRNAs for neurotrophic factors (NGF, BDNF, NT-3, and GDNF) and their receptors (p75NGFR, trkA, trkB, and trkC) in the adult human peripheral nervous system and nonneural tissues.Neurochem Res. 1996; 21: 929-938Crossref PubMed Scopus (224) Google Scholar). We have demonstrated that BDNF is present in the follicular fluid of normally cycling women and in the preovulatory follicles of women undergoing assisted reproductive technology (ART), namely, in vitro fertilization (IVF) (4Seifer D.B. Feng B. Shelden R.M. Immunocytochemical evidence for the presence and location of the neurotrophin-Trk receptor family in adult human preovulatory ovarian follicles.Am J Obstet Gynecol. 2006; 194 (discussion 1134–26): 1129-1134Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar, 5Seifer D.B. Feng B. Shelden R.M. Chen S. Dreyfus C.F. Neurotrophin-4/5 and neurotrophin-3 are present within the human ovarian follicle but appear to have different paracrine/autocrine functions.J Clin Endocrinol Metab. 2002; 87: 4569-4571Crossref PubMed Scopus (39) Google Scholar, 6Seifer D.B. Feng B. Shelden R.M. Chen S. Dreyfus C.F. Brain-derived neurotrophic factor: a novel human ovarian follicular protein.J Clin Endocrinol Metab. 2002; 87: 655-659Crossref PubMed Scopus (71) Google Scholar, 7Seifer D.B. Lambert-Messerlian G. Schneyer A.L. Ovarian brain-derived neurotrophic factor is present in follicular fluid from normally cycling women.Fertil Steril. 2003; 79: 451-452Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar). We have also shown that the secretion of BDNF from granulosa cells is enhanced by c-AMP in a dose-dependent manner (6Seifer D.B. Feng B. Shelden R.M. Chen S. Dreyfus C.F. Brain-derived neurotrophic factor: a novel human ovarian follicular protein.J Clin Endocrinol Metab. 2002; 87: 655-659Crossref PubMed Scopus (71) Google Scholar).Previous studies have revealed that circulating BDNF reflects eating behavior and the development of obesity in females, with BDNF being low in anorexia and bulimia nervosa (8Monteleone P. Fabrazzo M. Martiadis V. Serritella C. Pannuto M. Maj M. Circulating brain-derived neurotrophic factor is decreased in women with anorexia and bulimia nervosa but not in women with binge-eating disorder: relationships to co-morbid depression, psychopathology and hormonal variables.Psychol Med. 2005; 35: 897-905Crossref PubMed Scopus (95) Google Scholar, 9Nakazato M. Hashimoto K. Shimizu E. Kumakiri C. Koizumi H. Okamura N. et al.Decreased levels of serum brain-derived neurotrophic factor in female patients with eating disorders.Biol Psychiatry. 2003; 54: 485-490Abstract Full Text Full Text PDF PubMed Scopus (133) Google Scholar, 10Monteleone P. Tortorella A. Martiadis V. Serritella C. Fuschino A. Maj M. Opposite changes in the serum brain-derived neurotrophic factor in anorexia nervosa and obesity.Psychosom Med. 2004; 66: 744-748Crossref PubMed Scopus (93) Google Scholar, 11Ribases M. Gratacos M. Fernandez-Aranda F. Bellodi L. Boni C. Anderluh M. et al.Association of BDNF with anorexia, bulimia and age of onset of weight loss in six European populations.Hum Mol Genet. 2004; 13: 1205-1212Crossref PubMed Scopus (185) Google Scholar) and elevated in adult obese women (10Monteleone P. Tortorella A. Martiadis V. Serritella C. Fuschino A. Maj M. Opposite changes in the serum brain-derived neurotrophic factor in anorexia nervosa and obesity.Psychosom Med. 2004; 66: 744-748Crossref PubMed Scopus (93) Google Scholar, 12Bullo M. Peeraully M.R. Trayhurn P. Folch J. Salas-Salvado J. Circulating nerve growth factor levels in relation to obesity and the metabolic syndrome in women.Eur J Endocrinol. 2007; 157: 303-310Crossref PubMed Scopus (97) Google Scholar, 13El-Gharbawy A.H. Adler-Wailes D.C. Mirch M.C. Theim K.R. Ranzenhofer L. Tanofsky-Kraff M. et al.Serum brain-derived neurotrophic factor concentrations in lean and overweight children and adolescents.J Clin Endocrinol Metab. 2006; 91: 3548-3552Crossref PubMed Scopus (86) Google Scholar, 14Suwa M. Kishimoto H. Nofuji Y. Nakano H. Sasaki H. Radak Z. et al.Serum brain-derived neurotrophic factor level is increased and associated with obesity in newly diagnosed female patients with type 2 diabetes mellitus.Metabolism. 2006; 55: 852-857Abstract Full Text Full Text PDF PubMed Scopus (152) Google Scholar, 15Lommatzsch M. Zingler D. Schuhbaeck K. Schloetcke K. Zingler C. Schuff-Werner P. et al.The impact of age, weight and gender on BDNF levels in human platelets and plasma.Neurobiol Aging. 2005; 26: 115-123Crossref PubMed Scopus (645) Google Scholar). This might imply that circulating BDNF level is related to the total body fat mass. It is therefore possible that the BDNF level increases in obesity to compensate for its associated pathophysiologic conditions because of its potential role in improving energy metabolism and suppressing food intake (14Suwa M. Kishimoto H. Nofuji Y. Nakano H. Sasaki H. Radak Z. et al.Serum brain-derived neurotrophic factor level is increased and associated with obesity in newly diagnosed female patients with type 2 diabetes mellitus.Metabolism. 2006; 55: 852-857Abstract Full Text Full Text PDF PubMed Scopus (152) Google Scholar). Given that more reproductive-aged women are undergoing bariatric surgery (2Santry H.P. Gillen D.L. Lauderdale D.S. Trends in bariatric surgical procedures.JAMA. 2005; 294: 1909-1917Crossref PubMed Scopus (772) Google Scholar), that BDNF may have a role in supporting granulosa cell oocyte communication within the follicle (7Seifer D.B. Lambert-Messerlian G. Schneyer A.L. Ovarian brain-derived neurotrophic factor is present in follicular fluid from normally cycling women.Fertil Steril. 2003; 79: 451-452Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar), that BDNF seems to mediate LH and hCG actions in promoting preovulatory oocyte meiotic maturation (16Feng B. Chen S. Shelden R.M. Seifer D.B. Effect of gonadotropins on brain-derived neurotrophic factor secretion by human follicular cumulus cells.Fertil Steril. 2003; 80: 658-659Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar), and that there is growing research for the role of circulating BDNF and ART (16Feng B. Chen S. Shelden R.M. Seifer D.B. Effect of gonadotropins on brain-derived neurotrophic factor secretion by human follicular cumulus cells.Fertil Steril. 2003; 80: 658-659Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar, 17Monteleone P. Artini P.G. Simi G. Cela V. Casarosa E. Begliuomini S. et al.Brain derived neurotrophic factor circulating levels in patients undergoing IVF.J Assist Reprod Genet. 2007; 24: 477-480Crossref PubMed Scopus (18) Google Scholar), it would be insightful to assess changes in plasma BDNF after "dramatic" weight loss caused by bariatric surgery in morbidly obese women. We hypothesized that BDNF levels would drop after surgical weight loss secondary to a decrease in total body fat mass.Materials and methodsEighteen morbidly obese women who underwent bariatric surgery were enrolled in a prospective study evaluating pre- and postoperative BDNF levels. The study was approved by the institutional review boards of Maimonides Medical Center and Women and Infants Hospital, and patients signed informed consent. A phone call was placed to all the female patients scheduled for bariatric surgery over a 15-month period, and they were each asked to participate. Of >80 women called, 18 agreed to participate. Because BDNF is inversely related to menopausal status (18Begliuomini S. Casarosa E. Pluchino N. Lenzi E. Centofanti M. Freschi L. et al.Influence of endogenous and exogenous sex hormones on plasma brain-derived neurotrophic factor.Hum Reprod. 2007; 22: 995-1002Crossref PubMed Scopus (178) Google Scholar), we divided the patients into premenopausal and postmenopausal groups, and because BDNF might change differently according to the type of surgery, we have subdivided the participants according to either gastric bypass or gastric banding.Patients were recruited before surgery to give a blood sample and complete a questionnaire that included information regarding demographics, medical, gynecologic, surgical, and social history and drug intake. A participant was considered menopausal if she had no menstrual periods for 12 consecutive months and her mullerian inhibiting substance level was negligible (<0.1 ng/mL). None of the patients were on hormonal medications at the time of their blood draw, and sample collection was not timed with respect to the menstrual cycle because of the poor compliance of the population studied (19Poole N.A. Al Atar A. Kuhanendran D. Bidlake L. Fiennes A. McCluskey S. et al.Compliance with surgical after-care following bariatric surgery for morbid obesity: a retrospective study.Obes Surg. 2005; 15: 261-265Crossref PubMed Scopus (86) Google Scholar), the high risk of amenorrhea associated with morbid obesity (20Escobar-Morreale H.F. Botella-Carretero J.I. Alvarez-Blasco F. Sancho J. San Millan J.L. The polycystic ovary syndrome associated with morbid obesity may resolve after weight loss induced by bariatric surgery.J Clin Endocrinol Metab. 2005; 90: 6364-6369Crossref PubMed Scopus (284) Google Scholar), and the high chance of having menstrual changes after surgical weight loss (21Teitelman M. Grotegut C.A. Williams N.N. Lewis J.D. The impact of bariatric surgery on menstrual patterns.Obes Surg. 2006; 16: 1457-1463Crossref PubMed Scopus (138) Google Scholar, 22Deitel M. Stone E. Kassam H.A. Wilk E.J. Sutherland D.J. Gynecologic-obstetric changes after loss of massive excess weight following bariatric surgery.J Am Coll Nutr. 1988; 7: 147-153Crossref PubMed Scopus (206) Google Scholar). Samples were taken approximately 1 or 2 weeks before the patients underwent the bariatric surgical procedure; postoperative samples were taken a mean (±SE) of 87 ± 7 days (3 months) after the operation. Blood was drawn into 7-mL Vacutainer tubes containing 0.5 mL of 3.8% sodium citrate. We preferred to analyze plasma rather than serum BDNF concentration to avoid possible interindividual variations connected with physiologic and/or pathologic alterations of platelets count (platelets are known to be one of the major human BDNF storage sites) (23Yamamoto H. Gurney M.E. Human platelets contain brain-derived neurotrophic factor.J Neurosci. 1990; 10: 3469-3478Crossref PubMed Google Scholar). The blood samples were processed by centrifuge after collection, and then all samples were frozen at −80°C until they were analyzed for plasma BDNF levels. There were no differences in the pre- and postoperative sample collection processes.Brain-derived neurotrophic factor levels were determined in duplicate using the commercially available BDNF Emax immunoassay system (Promega Corp., Madison, WI). The ELISAs were performed according to the manufacturer's protocol and as previously described (6Seifer D.B. Feng B. Shelden R.M. Chen S. Dreyfus C.F. Brain-derived neurotrophic factor: a novel human ovarian follicular protein.J Clin Endocrinol Metab. 2002; 87: 655-659Crossref PubMed Scopus (71) Google Scholar). The BDNF assay lower limit of sensitivity was 16 pg/mL and intrassay coeffcients of variation were <15%.Data are expressed as mean ± SE. The Wilcoxon signed ranked test was used to compare pre- to postoperative BDNF levels. Differences in pre- and postoperative levels of BDNF were compared using the Mann-Whitney rank sum test. The correlations between BDNF, age, and body mass index (BMI) were calculated using Spearman rank correlation coefficients. Exact probabilities were computed because of the small sample size. Computations were done using the SPSS Exact Statistic module. A value of P<.05 was considered statistically significant.ResultsClinical and demographic characteristics of the participants are shown in Table 1. There were 12 premenopausal women and 6 postmenopausal women in this cohort. Plasma mean BDNF concentrations decreased by 38% after surgery (7,708.0 ± 1,145.3 pg/mL preoperatively to 4,146.3 ± 705.4 pg/mL postoperatively, P=.009) in all the participants, whereas BMI dropped by 12.6%. Plasma BDNF decreased by 54% in the premenopausal group (7,988.1 ± 1,551.4 pg/mL preoperatively to 3,616.5 ± 813.2 pg/mL postoperatively, P=.026), whereas BMI dropped by 13.6%, and plasma BDNF decreased by 17% in the postmenopausal group, although that drop was not significant (7,147.6 ± 1,641.5 pg/mL preoperatively to 5,205.8 ± 1,352.2 pg/mL postoperatively, P=.148), whereas BMI dropped by 10.4%.Table 1Demographics and clinical profiles of the participants.All participants (N = 18)Premenopausal (N = 12)Postmenopausal (N = 6)Age in yearsaRange for ages 25–59 years, and for body mass index of 36.4–68.2 kg/m2 preoperatively and 30.4–58.2 kg/m2 postoperatively. mean (SE)40.05 (2.46)34.33 (1.95)51.5 (2.37)Type of bariatric surgery Gastric banding1275 Gastric bypass651BMI in kg/m2aRange for ages 25–59 years, and for body mass index of 36.4–68.2 kg/m2 preoperatively and 30.4–58.2 kg/m2 postoperatively. Preoperative-mean (SE)48.21 (1.96)48.35 (2.47)47.95 (3.5) Postoperative-mean (SE)42.14 (1.88)41.75 (2.6)42.93 (2.48)Note: BMI = body mass index; SE = standard error.a Range for ages 25–59 years, and for body mass index of 36.4–68.2 kg/m2 preoperatively and 30.4–58.2 kg/m2 postoperatively. Open table in a new tab Twelve patients had undergone gastric banding procedures and six had gastric bypass. Because patients who had bypass (preoperative BMI = 50 ± 4.0 and postoperative BMI = 40 ± 4.0; P=.0001) lost significantly more weight than those with a banding procedure (preoperative BMI = 47 ± 2.3 and postoperative BMI = 43 ± 2.1; P=.0001; 20% and 8.5% drop in BMI in the bypass and the banding group, respectively), we also performed the analysis according to the surgery type. Although BDNF decreased in both banding (from 7,893 ± 1,507 pg/mL preoperative to 4,831 ± 978 pg/mL postoperative; P=.09) and bypass groups (from 7,337 ± 1,837 pg/mL preoperative to 2,777 ± 552 pg/mL postoperative; P=.06), because of the small sample sizes these changes were not significant. The drop in BDNF was greater in the bypass (62% drop) than the banding group (39% drop) but once again because of the small sample size the difference did not achieve statistical significance (P=.49) (Table 2). When Spearman correlation was performed, there was no correlation between the amount of weight loss and the drop in BDNF and no correlation between age and BDNF.Table 2Summary of plasma BDNF levels.Preoperative BDNF levels (pg/mL)Postoperative BDNF levels (pg/mL)All participants (N = 18)7708.0 ± 1145.34146.3 ± 705.4aP<.05.Premenopausal group (N = 12)7988.1 ± 1551.43616.5 ± 813.2aP<.05.Postmenopausal group (N = 6)7147.6 ± 1641.55205.8 ± 1352.2Banding group (N = 12)7893 ± 15074831 ± 978Bypass group (N = 6)7337 ± 18372777 ± 552Note: Data are expressed as mean ± SE.a P<.05. Open table in a new tab DiscussionWe measured plasma BDNF in a cohort of morbidly obese women who underwent surgical weight loss and have shown a drop in the BDNF levels. Studies on animal models have revealed that endogenous BDNF levels significantly drop in the dorsal vagal complex (DVC) and in the ventromedial hypothalamus (VMH) in the starvation state (24Bariohay B. Lebrun B. Moyse E. Jean A. Brain-derived neurotrophic factor plays a role as an anorexigenic factor in the dorsal vagal complex.Endocrinology. 2005; 146: 5612-5620Crossref PubMed Scopus (125) Google Scholar). Bariohay et al. (24Bariohay B. Lebrun B. Moyse E. Jean A. Brain-derived neurotrophic factor plays a role as an anorexigenic factor in the dorsal vagal complex.Endocrinology. 2005; 146: 5612-5620Crossref PubMed Scopus (125) Google Scholar) revealed that within the DVC, BDNF protein content decreased by 40% after 48 h fasting. Blood BDNF levels were not measured in those two studies, but because BDNF crosses the blood–brain barrier, and because blood BDNF has been reported to reflect central BDNF levels in animal models (25Karege F. Schwald M. Cisse M. Postnatal developmental profile of brain-derived neurotrophic factor in rat brain and platelets.Neurosci Lett. 2002; 328: 261-264Crossref PubMed Scopus (679) Google Scholar), we hypothesize that the postbariatric surgery period, considered a relative starvation state, could be an explanation for the low plasma BDNF levels we found in this study. A tempting hypothesis for this drop in BDNF postbariatric surgery is that it relates to changes in leptin. The postbariatric surgery period is considered a low leptin state, and a strong positive correlation has been shown between leptin and BDNF, and BDNF may constitute a common downstream effector of leptin through the melanocortin 4 receptor (MC4R) (22Deitel M. Stone E. Kassam H.A. Wilk E.J. Sutherland D.J. Gynecologic-obstetric changes after loss of massive excess weight following bariatric surgery.J Am Coll Nutr. 1988; 7: 147-153Crossref PubMed Scopus (206) Google Scholar). In fact, infusion of leptin centrally induced an increase in BDNF content within the DVC (22Deitel M. Stone E. Kassam H.A. Wilk E.J. Sutherland D.J. Gynecologic-obstetric changes after loss of massive excess weight following bariatric surgery.J Am Coll Nutr. 1988; 7: 147-153Crossref PubMed Scopus (206) Google Scholar). The role of leptin in the association between surgical weight loss and BDNF needs to be explored.Blood BDNF levels of normal-weight patients have been compared with those of obese patients, although the results have not been uniform. Monteleone et al. (10Monteleone P. Tortorella A. Martiadis V. Serritella C. Fuschino A. Maj M. Opposite changes in the serum brain-derived neurotrophic factor in anorexia nervosa and obesity.Psychosom Med. 2004; 66: 744-748Crossref PubMed Scopus (93) Google Scholar) found that BDNF levels were significantly higher in obese women (mean BMI of 37) than in normal BMI patients. However, El-Gharbawy et al. (13El-Gharbawy A.H. Adler-Wailes D.C. Mirch M.C. Theim K.R. Ranzenhofer L. Tanofsky-Kraff M. et al.Serum brain-derived neurotrophic factor concentrations in lean and overweight children and adolescents.J Clin Endocrinol Metab. 2006; 91: 3548-3552Crossref PubMed Scopus (86) Google Scholar) reported that serum BDNF was lower in extremely overweight children and adolescents (mean BMI of 36) than those of normal weight. Further, although Suwa et al. (14Suwa M. Kishimoto H. Nofuji Y. Nakano H. Sasaki H. Radak Z. et al.Serum brain-derived neurotrophic factor level is increased and associated with obesity in newly diagnosed female patients with type 2 diabetes mellitus.Metabolism. 2006; 55: 852-857Abstract Full Text Full Text PDF PubMed Scopus (152) Google Scholar) showed a positive correlation between serum BDNF levels and BMI in female patients (mean BMI of 26), Lommatzsch et al. (15Lommatzsch M. Zingler D. Schuhbaeck K. Schloetcke K. Zingler C. Schuff-Werner P. et al.The impact of age, weight and gender on BDNF levels in human platelets and plasma.Neurobiol Aging. 2005; 26: 115-123Crossref PubMed Scopus (645) Google Scholar) showed a negative correlation between plasma BDNF levels and weight in adult patients (median BMI of 24). A study by Bullo et al. (12Bullo M. Peeraully M.R. Trayhurn P. Folch J. Salas-Salvado J. Circulating nerve growth factor levels in relation to obesity and the metabolic syndrome in women.Eur J Endocrinol. 2007; 157: 303-310Crossref PubMed Scopus (97) Google Scholar), including morbidly obese patients, showed that BDNF seems to be more related to lipid profile than to BMI in female patients (morbidly obese group with mean BMI of 47). In our cohort of morbidly obese women, we have shown that there is a greater drop in BDNF in the bypass group compared with the banding group, with the bypass group having lost significantly more weight than the banding group. We have also found that there is a nearly significant correlation between the amount of weight loss and the drop in BDNF in the banding group. However, lipid data were not available for these patients.Most of studies on the relationship between BDNF and age have found that BDNF decreases with age. Lommatzsch et al. (15Lommatzsch M. Zingler D. Schuhbaeck K. Schloetcke K. Zingler C. Schuff-Werner P. et al.The impact of age, weight and gender on BDNF levels in human platelets and plasma.Neurobiol Aging. 2005; 26: 115-123Crossref PubMed Scopus (645) Google Scholar) showed a negative correlation between plasma BDNF level and age in 140 healthy adults (age range 20–60 years old). Begliuomini et al. (18Begliuomini S. Casarosa E. Pluchino N. Lenzi E. Centofanti M. Freschi L. et al.Influence of endogenous and exogenous sex hormones on plasma brain-derived neurotrophic factor.Hum Reprod. 2007; 22: 995-1002Crossref PubMed Scopus (178) Google Scholar) showed that plasma BDNF is significantly lower in postmenopausal women compared with fertile women, and found that in the postmenopausal group BDNF is negatively correlated with age. Ziegenhorn et al. (26Ziegenhorn A.A. Schulte-Herbruggen O. Danker-Hopfe H. Malbranc M. Hartung H.D. Anders D. et al.Serum neurotrophins—a study on the time course and influencing factors in a large old age sample.Neurobiol Aging. 2007; 28: 1436-1445Crossref PubMed Scopus (226) Google Scholar) showed a negative correlation between serum BDNF and age in a large elderly cohort (age >70 years old). Additionally, studies on animal models revealed a decrease in BDNF levels with aging in the hippocampus and hypothalamus (27Silhol M. Bonnichon V. Rage F. Tapia-Arancibia L. Age-related changes in brain-derived neurotrophic factor and tyrosine kinase receptor isoforms in the hippocampus and hypothalamus in male rats.Neuroscience. 2005; 132: 613-624Crossref PubMed Scopus (164) Google Scholar). In our cohort of morbidly obese women, plasma BDNF levels at baseline were lower in the postmenopausal group compared with the premenopausal group (although it did not reach statistical significance, most likely because of the small number of participants) but we did not find any correlation between BDNF and age either pre- or postoperatively. The absence of statistically significant correlations in the present study may partly result from the small sample size. However, the small sample size would not result in low correlation coefficients if indeed there were strong correlations in the population. Another possible explanation to the fact that BDNF dropped significantly in the premenopausal group but not in the postmenopausal group is that more patients had bypass surgery in the first group (five out of seven) than in the second group (one out of five), and ultimately lost more weight.BDNF has been shown to be important in the development of mouse oocyte into preimplantation embryos because it promotes the nuclear and cytoplasmic maturation of the oocyte (28Kawamura K. Kawamura N. Mulders S.M. Sollewijn Gelpke M.D. Hsueh A.J. Ovarian brain-derived neurotrophic factor (BDNF) promotes the development of oocytes into preimplantation embryos.Proc Natl Acad Sci USA. 2005; 102: 9206-9211Crossref PubMed Scopus (155) Google Scholar). A recent study determining follicular-fluid BDNF levels in women undergoing ART for different etiologies of infertility revealed that patients with a history of endometriosis had significantly lower levels of BDNF, that patients with diminished ovarian reserve had lower levels of BDNF (not statistically significant) and that women with PCOS and unexplained infertility had no changes in BDNF levels when compared with the control group (male factor infertility) (29Buyuk E. Seifer D.B. Follicular-fluid neurotrophin levels in women undergoing assisted reproductive technology for different etiologies of infertility.Fertil Steril. 2008 Jan 25; ([Epub ahead of print])Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar). The investigators postulated that the low levels of follicular-fluid BDNF in endometriosis patients might be associated with the poor oocyte quality and poor fertility status associated with endometriosis. Another study demonstrated that LH and hCG in vitro enhanced BDNF secretion by cumulus cells, and that human follicular-fluid BDNF levels are significantly higher in ART cycles (with hCG administration) than in natural cycles (without hCG administration) (16Feng B. Chen S. Shelden R.M. Seifer D.B. Effect of gonadotropins on brain-derived neurotrophic factor secretion by human follicular cumulus cells.Fertil Steril. 2003; 80: 658-659Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar). Little is known regarding ovarian BDNF levels and IVF success.In conclusion, plasma BDNF significantly dropped in bariatric surgery patients after rapid weight loss, both when all participants were combined and when the premenopausal group was looked at in isolation. Although there was also a drop in BDNF in the postmenopausal patients and separately in the banding and the bypass groups, because of small subset sizes, the differences did not reach significance at traditional levels. The decline in levels of BDNF was greater in those who had bypass surgery rather than banding. This suggests that changes in circulating BDNF in obesity, and after surgical weight loss are likely secondary to an altered energy balance. One hypothesis could be that in obesity, increased levels of plasma BDNF may represent an adaptive mechanism to counteract the condition of positive energy imbalance by stimulating energy expenditure and decreasing food ingestion (10Monteleone P. Tortorella A. Martiadis V. Serritella C. Fuschino A. Maj M. Opposite changes in the serum brain-derived neurotrophic factor in anorexia nervosa and obesity.Psychosom Med. 2004; 66: 744-748Crossref PubMed Scopus (93) Google Scholar); similarly, a BDNF reduction after surgical weight loss might promote food intake in an attempt to counterbalance the negative energy balance. The mechanism of action for BDNF in the regulation of food intake has yet to be established. Obesity is one of the fastest-growing health problems in the United States (1Christakis N.A. Fowler J.H. The spread of obesity in a large social network over 32 years.N Engl J Med. 2007; 357: 370-379Crossref PubMed Scopus (3333) Google Scholar). Bariatric surgery can lead to substantial weight reduction. Both the estimated number of bariatric surgical procedures and the number of practicing bariatric surgeons have increased markedly in the United States (2Santry H.P. Gillen D.L. Lauderdale D.S. Trends in bariatric surgical procedures.JAMA. 2005; 294: 1909-1917Crossref PubMed Scopus (772) Google Scholar). Brain-derived neurotrophic factor (BDNF), a protein that belongs to the neurotrophin family and originally described in the nervous system, has been shown to be expressed in nonneuronal tissues like the ovaries, and to be present in plasma (3Yamamoto M. Sobue G. Yamamoto K. Terao S. Mitsuma T. Expression of mRNAs for neurotrophic factors (NGF, BDNF, NT-3, and GDNF) and their receptors (p75NGFR, trkA, trkB, and trkC) in the adult human peripheral nervous system and nonneural tissues.Neurochem Res. 1996; 21: 929-938Crossref PubMed Scopus (224) Google Scholar). We have demonstrated that BDNF is present in the follicular fluid of normally cycling women and in the preovulatory follicles of women undergoing assisted reproductive technology (ART), namely, in vitro fertilization (IVF) (4Seifer D.B. Feng B. Shelden R.M. Immunocytochemical evidence for the presence and location of the neurotrophin-Trk receptor family in adult human preovulatory ovarian follicles.Am J Obstet Gynecol. 2006; 194 (discussion 1134–26): 1129-1134Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar, 5Seifer D.B. Feng B. Shelden R.M. Chen S. Dreyfus C.F. Neurotrophin-4/5 and neurotrophin-3 are present within the human ovarian follicle but appear to have different paracrine/autocrine functions.J Clin Endocrinol Metab. 2002; 87: 4569-4571Crossref PubMed Scopus (39) Google Scholar, 6Seifer D.B. Feng B. Shelden R.M. Chen S. Dreyfus C.F. Brain-derived neurotrophic factor: a novel human ovarian follicular
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