Anorexia nervosa and reproduction: connecting brain to gonads

Anorexia nervosa (AN) is a psychiatric disorder that predominantly affects young women and is characterized by low caloric intake and a major dissatisfaction with one’s body image. It is often overlooked and, while patients and family seek medical help, emaciation and nutritional misbalances may become extreme and potentially life threatening. Among the many somatic complications, an accumulation of early endocrine adaptations occurs, leading to functional amenorrhea and impaired reproduction as a result of dysfunction of the hypothalamic-pituitary-ovarian axis. Even though these conditions are reversible, long-term consequences may affect the fertility of women with AN and can lead to maternal and fetal complications during pregnancy and birth. This review presents the clinical particularities of reproduction in the context of AN, along with the possible pathophysiological mechanisms involved

Linking the brain and bone through fat

Over the past years, bone and adipose tissue have gained interest from researchers in the light of their secretory profiles, being able to produce active molecules, with the final effect of regulating energy homeostasis. Both adipocytes and osteoblasts originate in the pluripotent mesenchymal stem cell and this common origin has been proposed as the core of the fat-bone relationship. The central nervous system might be the third player in this association, capable of integrating signals. Numerous adipose tissue secreted factors that influence energy homeostasis and bone have been described: leptin, adiponectin, lipocalin 2, and inflammatory cytokines (e.g. IL-1, IL-6 and TNF-α). Similarly, osteocalcin, the most abundant bone protein, has been shown to elicit numerous central and peripheral endocrine functions. In this paper, we provide a review of the current literature regarding the bone-adipose tissue-central nervous system axis and a brief description of the several underlying molecular mechanisms

Anorexia nervosa and reproduction: connecting brain to gonads

Anorexia nervosa (AN) is a psychiatric disorder that predominantly affects young women and is characterized by low caloric intake and a major dissatisfaction with one’s body image. It is often overlooked and, while patients and family seek medical help, emaciation and nutritional misbalances may become extreme and potentially life threatening. Among the many somatic complications, an accumulation of early endocrine adaptations occurs, leading to functional amenorrhea and impaired reproduction as a result of dysfunction of the hypothalamic-pituitary-ovarian axis. Even though these conditions are reversible, long-term consequences may affect the fertility of women with AN and can lead to maternal and fetal complications during pregnancy and birth. This review presents the clinical particularities of reproduction in the context of AN, along with the possible pathophysiological mechanisms involved

The Connections Between Androgens and Adipose Tissue Function in Polycystic Ovary Syndrome Patients

Few studies reported that androgens levels could be among the regulators of adipose tissue hormones. Polycystic ovary syndrome (PCOS) is characterized by both increased adiposity and hyperandrogenism, but the relationship between androgens levels and adipokines in PCOS has not been well characterized. Our aim was to study the relationship between leptin, adiponectin, total testosterone, sex hormone binding globulin (SHBG) and free androgen index (FAI) in PCOS patients. We conducted a cross-sectional study on 131 PCOS patients (mean age 24 [6] yrs, mean body mass index (BMI) 25.8 [10.44] kg/m2) diagnosed based on Rotterdam Consensus criteria. All the patients were evaluated by clinical, paraclinical and hormonal exam. HOMA-IR was calculated for all the patients. Leptin was positively associated with age (p<0.05), BMI (p<0,0001), waist-hip ratio (WHR) (p<0.0001), waist circumference (WC) (p<0,0001), HOMA-IR (p<0,0001), insulinemia (p<0.0001) and FAI (p<0,0001) and negatively with SHBG (p<0.0001). Adiponectin was negatively associated with age (p<0.05), BMI (p<0,0001), WC (p<0,0001), WHR (p<0,0001), HOMA-IR (p<0,0001), insulinemia (p<0.0001) and FAI (p<0,005) and positively associated with SHBG (p<0,0001). Both adipokines were not correlated with total testosterone. The association between serum leptin and FAI/SHBG was lost after adjustment for age and body mass index. In turn the relationship between leptin and FAI, but not SHBG was independent of HOMA-IR. Circulating adiponectin was associated with SHBG independently of adiposity and HOMA-IR, but the association with FAI was lost after adjustment for HOMA-IR. In conlusion, circulating adipokines are correlated with FAI and SHBG serum levels. This association seems to be mediated by adiposity for leptin. Although the link between adiponectin and FAI is probably due to insulin resistance, SHBG seems to directly modulate adiponectin production

Ekspresja adiponektyny w otyłości trzewnej jest istotnym wyznacznikiem insulinooporności w otyłości olbrzymiej

Introduction: Visceral adiposity is associated with decreased serum adiponectin levels, peripheral resistance to insulin and an increased risk of cardio-metabolic complications. However, the link between adiponectin expression in visceral adipose tissue (VAT), its serum levels and metabolic protection is controversial. The aim of this study was to investigate the relationship between the adiponectin gene expression in VAT and clinical and metabolic parameters in patients with severe obesity. Material and Methods: This is a cross-sectional study that included 51 severely obese patients (age 43.24±11.29 years, BMI 45.13±8.67 kg/m2), extensively evaluated clinically and biologically (metabolic tests, serum adiponectin measurements, HOMA-IR) before bariatric surgery. Omental adipose tissue was sampled during the intervention and the relative quantification of adiponectin gene expression was performed by real-time PCR, using beta-actin as reference gene. Results. Adiponectin mRNA in VAT was significantly higher in obese insulin-sensitive patients than in the rest of obese patients (p < 0.05) and negatively correlated with HOMA-IR (r =-0.354, p=0.016) and uric acid (r =-0.304, p=0.045). After adjustment for gender, TG/HDL ratio and uric acid, adiponectin expresion (β= -0.439, p=0.001), waist circumference (β=0.467, p=0.001) and serum adiponectin (β =-0.339, p=0.011) remained significantly associated with HOMA-IR, together explaining more than 50% of its variation. Conclusions. In severely obese patients, adiponectin gene expression in VAT is negatively correlated with serum levels of uric acid and is an independent determinant, together with anthropometric parameters of visceral obesity and serum adiponectin levels, of insulin resistance.Wstęp: Otyłość trzewna związana jest ze zmniejszonym stężeniem adiponektyny w surowicy krwi, obwodową opornością na działanie insuliny oraz ze zwiększonym ryzykiem powikłań sercowo-metabolicznych. Jednak związek między ekspresją adiponektyny w trzewnej tkance tłuszczowej, jej stężeniem w surowicy krwi a ochroną metaboliczną jest kwestią sporną. Celem niniejszej pracy było zbadanie związku między ekspresją genu adiponektyny w trzewnej tkance tłuszczowej a klinicznymi i metabolicznymi parametrami pacjentów ze znaczną otyłością. Materiał i metody: To przekrojowe badanie obejmowało 51 znacznie otyłych pacjentów (wiek 43,24 ± 11,29 roku, BMI 45,13 ± 8,67 kg/m2), szczegółowo ocenionych pod względem klinicznym i biologicznym (testy metaboliczne, pomiary stężenia adiponektyny w surowicy krwi, wskaźnik HOMA-IR) przed operacją bariatryczną. Podczas operacji pobrano tkankę tłuszczową sieci. Względna ocena ilościowa ekspresji genu adiponektyny była przeprowadzona metodą PCR w czasie rzeczywistym. Wyniki: Poziom mRNA adiponektyny w trzewnej tkance tłuszczowej był znacząco wyższy u otyłych pacjentów wrażliwych na insulinę niż u pozostałych otyłych pacjentów (p &lt; 0,05) oraz ujemnie skorelowany ze wskaźnikiem HOMA-IR (r = –0,354, p = 0,016) i kwasem moczowym (r = –0,304, p = 0.045). Po uwzględnieniu płci, wskaźnika TG/HDL i kwasu moczowego, ekspresja adiponektyny (β = –0,439, p = 0,001), obwód talii (β = 0,467, p = 0,001) i poziom adiponektyny w surowicy krwi (β = –0,339, p = 0,011) pozostały istotnie związane ze wskaźnikiem HOMA-IR, łącznie wyjaśniając ponad 50% jego wariancji. Wnioski: W przypadku znacznie otyłych pacjentów ekspresja genu adiponektyny w trzewnej tkance tłuszczowej jest ujemnie skorelowana ze stężeniem kwasu moczowego w surowicy krwi i razem z antropometrycznymi parametrami otyłości trzewnej oraz stężeniem adiponektyny w surowicy krwi jest niezależnym wyznacznikiem insulinooporności

Laparoscopic Sleeve Gastrectomy Improves Reproductive Hormone Levels in Morbidly Obese Males -A Series of 28 Cases

Rezumat Gastrectomia longitudinalã laparoscopicã îmbunãtãåeaete nivelul hormonilor reproductivi la bãrbaåii cu obezitate morbidã -o serie de 28 cazuri Introducere: Bãrbaåii obezi prezintã frecvent reduceri ale hormonilor androgeni ce pot fi modificate dupã scãderea ponderalã obåinutã prin chirurgie bariatricã. Gastrectomia longitudinalã laparoscopicã (GLL) a fost folositã frecvent în ultimul deceniu pentru tratarea obezitãåii severe. Scopul studiului a fost evaluarea modificãrilor hormonilor reproductivi dupã GLL

PROPEPTIDUL AMINO-TERMINAL AL PROCOLAGENULUI TIP I LA PACIENŢII CU DEFICIT DE HORMON DE CREŞTERE ÎN PERIOADA DE TRANZIŢIE

Introducere. Achiziţia de masă osoasă continuă şi după atingerea taliei finale în perioada de tranziţie. Deficitul de hormon de creştere (GHD) pare să aibă un efect semnificativ asupra turnover-ului colagenului în timpul copilăriei şi mai puţin în timpul maturităţii. Propeptidul amino terminal al colagenului tip I (P1NP) este un marker de formare osoasă cu variabilitate intraindividuală scăzută faţă de IGF1. Subiecţi şi metodă. 17 pacienţi de sex masculin diagnosticaţi în timpul copilăriei cu GHD, retestaţi în perioada de tranziţie, au fost evaluaţi la minimum 3 luni de la întreruperea tratamentului cu GH. Am evaluat corelaţia P1NP cu IGF1. Am determinat puterea predictivă a P1NP în identificarea pacienţilor cu deficit de GH persistent. Rezultate. Am găsit o corelaţie pozitivă puternică între P1NP şi IGF-1 în grupul de pacienţi care au menţinut deficitul de GH în perioada de adult tânăr (r = 0,72, CI [0,02 la 0,94], p = 0,046). O valoare prag pentru P1NP de - 0,66 SDS prezice persistenţa deficitului de GH cu o sensibilitate de 62,5% CI [24,5 la 91,5], specificitate de 75% CI [47,6 la 92,7] şi AUC = 0,719 CI [0,5 la 0,881], p<0,05. Nu am găsit o diferenţă semnificativă atunci când am comparat AUC pentru cei 2 parametri (p = 0.29). Concluzii. În perioada de tranziţie, atunci când viteza de creştere nu mai este disponibilă, dinamica P1NP în timpul terapiei substitutive cu GH ar putea fi utilă în cuantificarea eficienţei tratamentului

Gęste mapowanie regionu VNTR genu insuliny w zespole policystycznych jajników w populacji kobiet z Europy Środkowej

Introduction: Insulin gene VNTR was associated with polycystic ovary syndrome (PCOS) in some studies but not in others. This couldb be due to the heterogeneity of the definition of PCOS and/or the use of inappropriate gene mapping strategies.Material and methods: In this investigation, the association of VNTR with PCOS was explored in a population of women from Central Europe (377 cases and 105 controls) in whom PCOS was diagnosed according to Rotterdam criteria. Seven SNPs: rs3842756 (G/A), rs3842755 (G/T), rs3842754 (C/T), rs3842753 (A/C), rs3842752 (C/T), rs3842748 (G/C), and rs689 (T/A) were genotyped in a portion of the population (160 cases and 95 controls) by sequencing or by SSO-PCR. Analysis of linkage disequilibrium (LD) pattern allowed selecting three tagSNPs (rs3842754, rs3842748, and rs689), which were genotyped in the rest of the population by KASPar.Results: Six haplotypes were reconstructed, among which three (h1, h2 and h6) were more frequent. Statistical analysis allowed observation of the association of the SNP rs3842748, through its GC genotype, with obesity in PCOS (P = 0.049; OR CI95% 1,59 [1.00–2.51]) and in classical PCOS (YPCOS) (P = 0.010), as well as the correlation of the SNP rs689 and the pair of haplotypes h1/h1 with higher levels of testosteronaemia in the PCOS group, although this was at the limit of significance (P = 0.054)Conclusion: These results are in accordance with some studies in literature and highlight the role of insulin gene VNTR in complex metabolic disorders. (Endokrynol Pol 2015; 66 (3): 198–206)Wstęp: W niektórych badaniach, zmienna liczba powtórzeń tandemowych (VNTR) genu insuliny była związana z zespołem policystycznych jajników (PCOS), lecz w innych taki związek nie występował. Mogło tak być z powodu heterogeniczności definicji PCOS i/lub stosowania nieprawidłowych strategii mapowania genów.Materiał i metody: W niniejszym badaniu, związek VNTR z PCOS zbadano w populacji kobiet pochodzących z Europy Środkowej (377 przypadków chorobowych oraz 105 osób kontrolnych), u których zdiagnozowano PCOS według kryteriów rotterdamskich. Siedem polimorfizmów pojedynczego nukleotydu (SNP): rs3842756 (G/A), rs3842755 (G/T), rs3842754 (C/T), rs3842753 (A/C), rs3842752 (C/T), rs3842748 (G/C), oraz rs689 (T/A) wytypowano w części populacji (160 przypadków chorobowych i 95 osób kontrolnych) poprzez sekwencjonowanie lub SSO-PCR. Analiza wzoru niezrównoważenia sprzężeń (LD) pozwoliła na selekcję trzech SNP znacznikowych (tagSNP) (rs3842754, rs3842748 i rs689), które wyselekcjonowano w pozostałej części populacji metodą KASPar.Wyniki: Sześć haplotypów odtworzono, z których 3 (h1, h2 i h6) występowały częściej. Analiza statystyczna pozwoliła na obserwację związku SNP rs3842748, poprzez genotyp GC, z otyłością w PCOS (P = 0,049; OR CI 95% 1,59 [1,00–2,51]) i klasycznym PCOS (YPCOS) (P = 0,010), jak również korelacji SNP rs689 i pary haplotypów h1/h1 z wyższym stężeniem testosteronemii w grupie PCOS, chociaż wynik ten znajdował się na granicy istotności (P = 0,054).Wnioski: Powyższe wyniki są zgodne z niektórymi badaniami w piśmiennictwie i podkreślają role VNTR genu insuliny w złożonych zaburzeniach metabolicznych. (Endokrynol Pol 2015; 66 (3): 198–206