Cell and molecular mechanisms behind diet-induced hypothalamic inflammation and obesity

© 2018 British Society for Neuroendocrinology Diet-induced obesity (DIO) is associated with chronic, low-grade inflammation in the hypothalamus, a key regulator of energy homeostasis. Current studies have revealed the involvement of different cell types, as well as cell and molecular mechanisms, that contribute to diet-induced hypothalamic inflammation (DIHI) and DIO. Subsequent to the discovery that high-fat diet and saturated fatty acids increase the expression of hypothalamic cytokines prior to weight gain, research has focused on understanding the cellular and molecular mechanisms underlying these changes, in addition to the role of inflammation in the pathogenesis of obesity. Recent studies have proposed that the inhibition of pro-inflammatory pathways in microglia and astrocytes is sufficient to protect against DIHI and prevent obesity. In addition, impairment of intracellular and epigenetic mechanisms, such as hypothalamic autophagy and changes in the methylation pattern of cer

Perinatal androgen exposure and adipose tissue programming: Is there an impact on body weight fate?

© 2015 Informa UK, Ltd. Obesity is a major concern in public health because it is one of the main risk factors for the development of non-transmissible chronic diseases. The fact that there is a clear sex dimorphism in normal body fat distribution points out the role of sex steroids as key factors in the regulation and function of the adipose cell. Androgens affect adipogenesis and fat metabolism in the adipose tissue of males and females. Hormonal disorders during pregnancy may affect the fetal tissues, with long-term implications leading to the development of pathologies during adult life. Obesity and metabolic disease are among these. In this regard, animal models have demonstrated an abnormal fat distribution and modifications in the size and function of adipose cells in the female and male offspring of mothers exposed to androgen excess during pregnancy

Valores de corte para los parámetros del perfil lipídico durante el embarazo: Scoping Review

Introducción y Objetivo: El aumento excesivo de los lípidos durante la gestación se asocia con complicaciones maternas y neonatales lo que sugiere su tamizaje(1). Sin embargo, no existe consenso sobre valores de referencia. Nuestro objetivo fue explorar la evidencia y recomendaciones de guías clínicas sobre valores de corte con potencial uso clínico para los parámetros del perfil lipídico durante el embarazo. Metodología: Revisión panorámica orientada según PRISMA(2). Se revisaron las bases de datos PubMed, Embase, Science Direct, SciELO, Google y Google Scholar. Se incluyeron trabajos originales y guías clínicas que entregaran al menos un valor de corte para triglicéridos, colesterol total, LDL o HDL durante el embarazo; entre los años 2010 y 2021. Los resultados fueron organizados en tablas. Resultados: Se incluyeron 31 referencias. De ellas, 11 trabajos establecieron valores de normalidad para diferentes rangos de edad gestacional, y mediante el uso de distintos percentiles. Si bien los datos fueron diversos, se observa que de forma general los parámetros aumentan con el progreso del embarazo. Adicionalmente, 12 estudios establecieron valores predictivos para complicaciones como preeclampsia, diabetes gestacional y alteraciones del crecimiento fetal, donde los triglicéridos tuvieron el mejor desempeño. La mayoría de las guías clínicas proponen como único valor de referencia 250 mg/dl tanto para colesterol total como para triglicéridos. Discusión/Conclusión: En vista de la diversidad de datos encontrados, es importante establecer consenso sobre los valores de referencia del perfil lipídico durante el embarazo que permita la correcta categorización de mujeres embarazadas como población de riesgo

Prenatal exposure to androgens as a factor of fetal programming La exposición prenatal a andrógenos como factor de reprogramación fetal

Both epidemiological and clinical evidence suggest a relationship between the prenatal environment and the risk of developing diseases during adulthood. The first observations about this relationship showed that prenatal growth retardation or stress conditions during fetal life were associated to cardiovascular, metabolic and other diseases in later life. However, not only those conditions may have lasting effects after birth. Growing evidence suggests that prenatal exposure to steroids (either of fetal or maternal origin) could be another source of prenatal programming with detrimental consequences during adulthood. We have recently demonstrated that pregnant women with polycystic ovary syndrome exhibit elevated androgen levels compared to normal pregnant women, which could provide an androgen excess for both female or male fetuses. We have further tested this hypothesis in an animal model of prenatal androgenization, finding that females born from androgenized mothers have a low bir

Metabolic Features Across the Female Life Span in Women with PCOS

Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine metabolic disorder and is presently considered a family pathology. It is associated with obesity, insulin resistance and metabolic syndrome. Racial, ethnic and environmental factors may be important in determining the clinical manifestations of this syndrome. Polycystic ovary syndrome is an exclusion diagnosis and, therefore, should be distinguished from the physiological changes typical for the age and from other hyperandrogenic disorders. Early diagnosis is important since this syndrome is associated with reproductive, oncologic and metabolic risks. Interestingly, the clinical features of this disorder may change throughout the lifespan of a PCOS woman, starting from adolescence to postmenopausal age. During the first decades of life the main features are in the reproductive area, while later in life metabolic abnormalities are more evident. While the assessment of insulin resistance is not part of the diagnosis of PCOS, it has been demonstrated that this metabolic component appears early in life and persists over time. Moreover during puberty and pregnancy, insulin resistance is exacerbated. Pregnancy represents an important stage, as the offspring of these patients may be reprogrammed and inherit some of the metabolic and reproductive features of their mothers. In the present review, we will focus on several metabolic aspects of the PCOS condition at different stages of life in a Chilean populationFondo Nacional de Desarrollo Cientifico y Tecnologico (National Fund for Scientific and Technological Research) Fondecyt 1970291 1030487 1050915 1071007 1110864 1151531 SOCHED (Chilean Society of Endocrinology and Diabetes) 2009-48 05 Alexander von Humboldt Foundatio

Maternal serum androgens in pregnant women with polycystic ovarian syndrome: possible implications in prenatal androgenization

Artículo de publicación ISIBACKGROUND: The aim of this study was to evaluate the peripheral serum androgen concentrations in normal and polycystic ovarian syndrome (PCOS) women during pregnancy, in order to establish if PCOS may induce gestational hyperandrogenism and therefore constitute a potential source of androgen excess for the fetus. METHODS: Twenty pregnant PCOS (PPCOS) women and 26 normal pregnant (NP) women of similar age with singleton pregnancies were selected for the study. During gestational weeks 10-16 and 22-28, a 2 h, 75 g oral glucose tolerance test (OGTT) was performed. For the OGTT, glucose and insulin were measured in each sample and testosterone, androstenedione, dehydroepiandrosterone sulphate (DHEAS), estradiol, progesterone and sex hormone-binding globulin were determined in the fasting sample. RESULTS: In the first study period (gestational weeks 10-16), the levels of androstenedione, testosterone and DHEAS and the free androgen index tended to be higher in the PCOS group. These differences became significant in the second study period (gestational weeks 22-28). In this second period, 2 h insulin concentrations were also significantly higher in PPCOS than in N-P women. CONCLUSIONS: The present study demonstrates a significant increase in androgen concentrations during pregnancy in PCOS women. We propose that these androgen concentrations could provide a potential source of androgen excess for the fetus, without leading to fetal virilization

Metformin during pregnancy: effects on offspring development and metabolic function

Maternal obesity during pregnancy and gestational diabetes mellitus (GDM) are both associated with of several postnatal diseases in the offspring, including obesity, early onset hypertension, diabetes mellitus, and reproductive alterations. Metformin is an oral drug that is being evaluated to treat GDM, obesity-associated insulin resistance, and polycystic ovary syndrome (PCOS) during pregnancy. The beneficial effects of metformin on glycemia and pregnancy outcomes place it as a good alternative for its use during pregnancy. In this line of thought, improving the metabolic status of the pregnant mother by using metformin should avoid the consequences of insulin resistance on the offspring's fetal and postnatal development. However, some human and animal studies have shown that metformin during pregnancy could amplify these alterations and be associated with excessive postnatal weight gain and obesity. In this minireview, we discuss not only the clinical and experimental evidence that supports the benefits of using metformin during pregnancy but also the evidence showing a possible negative impact of this drug on the offspring's development.Centro de Neurobiologia y Fisiopatologia Integrativa (CENFI), Universidad de Valparaiso DIUV-CI 01/200

Prevalence of Type II diabetes mellitus and insulin resistance in parents of women with polycystic ovary syndrome

Aims/hypothesis. Insulin resistance with increased risk of Type II (non-insulin-dependent) diabetes is a common feature of polycystic ovary syndrome (PCOS). To investigate antecedents of metabolic disorders in family members of patients with PCOS, we evaluated glucose tolerance and insulin resistance in parents of patients with PCOS compared to parents of healthy women. Methods. A total of 200 parents of women with clinical and hormonal evidence of PCOS (PCOSp) and 120 parents of healthy normally cycling women (HWp) were studied. A 75-g OGGT was performed and subjects were classified according to the World Health Organization (WHO) criteria (1999). Serum glucose and insulin were measured before the glucose load and 30, 60 and 120 min after. C-peptide and sex hormone-binding globulin were also determined before the glucose load. Insulin resistance was assessed by HOMA model and ISI composite. Results. The prevalence of Type II diabetes was 1.89-(1.06-3.38)-fold higher in PCOSp compare

Circulating gonadotropins and ovarian adiponectin system are modulated by acupuncture independently of sex steroid or β-adrenergic action in a female hyperandrogenic rat model of polycystic ovary syndrome

© 2015 Elsevier Ireland Ltd. Acupuncture with combined manual and low-frequency electrical stimulation, or electroacupuncture (EA), reduces endocrine and reproductive dysfunction in women with polycystic ovary syndrome (PCOS), likely by modulating sympathetic nerve activity or sex steroid synthesis. To test this hypothesis, we induced PCOS in rats by prepubertal implantation of continuous-release letrozole pellets (200 μg/day) or vehicle. Six weeks later, rats were treated for 5-6 weeks with low-frequency EA 5 days/week, subcutaneous injection of 17β-estradiol (2.0 μg) every fourth day, or a β-adrenergic blocker (propranolol hydrochloride, 0.1 mg/kg) 5 days/week. Letrozole controls were handled without needle insertion or injected with sesame oil every fourth day. Estrous cyclicity, ovarian morphology, sex steroids, gonadotropins, insulin-like growth factor I, bone mineral density, and gene and protein expression in ovarian tissue were measured. Low-frequency EA induced estrous-cycle

Serological markers of autoimmunity in pregnant women with polycystic ovary syndrome: A pilot study

Background. Gestational diabetes mellitus (GDM) is highly prevalent in women with polycystic ovary syndrome (PCOS). Women with GDM have considerable risk for developing both type 1 and type 2 diabetes. Aim. To evaluate the prevalence of anti-GAD65 and anti-IA2 auto-antibodies in Chilean pregnant women with GDM, normal pregnancy (NP) and with PCOS (PPCOS) to establish whether in PCOS women GDM is partially induced by autoantibodies. Methods. Women with singleton pregnancies matched by age and gestational age were included: 50 GDM, 59 NP and 50 PPCOS. During gestational weeks 22-28, a 2-h, 75 g oral glucose tolerance test was performed, with measurement of glucose, insulin, lipids and auto-antibodies. Results. A highly prevalence of anti-GAD65 antibodies (12%) was observed in women with GDM. PPCOS and NP women showed a similar distribution of anti-GAD65 antibodies (2.0% and 1.7%, respectively). Anti-IA2 antibodies were present in 4.0% of women with GDM, in 1.7% of NP women and 2.0% PPCO