Research Publications Archive - Foundation for Prader-Willi Research | Endocrinology/Growth Hormone

Hormonal, metabolic and skeletal phenotype of Schaaf-Yang syndrome: a comparison to Prader-Willi syndrome

BACKGROUND: Nonsense and frameshift mutations in the maternally imprinted, paternally expressed gene MAGEL2, located in the Prader-Willi critical region 15q11-15q13, have been reported to cause Schaaf-Yang syndrome (SYS), a genetic disorder that manifests as developmental delay/intellectual...

Loss of the imprinted, non-coding Snord116 gene cluster in the interval deleted in the Prader Willi syndrome results in murine neuronal and endocrine pancreatic developmental phenotypes

Global neurodevelopmental delay is a prominent characteristic of individuals with Prader-Willi syndrome (PWS). The neuromolecular bases for these delays are unknown. We identified neuroanatomical changes in the brains of mice deficient for a gene in the minimal critical deletion region for PWS...

The activity of the serotonin receptor 2C is regulated by alternative splicing

The central nervous system-specific serotonin receptor 2C (5HT2C) controls key physiological functions, such as food intake, anxiety, and motoneuron activity. Its deregulation is involved in depression, suicidal behavior, and spasticity, making it the target for antipsychotic drugs, appetite...

Deficiency in prohormone convertase PC1 impairs prohormone processing in Prader-Willi syndrome

Abstract Prader-Willi syndrome (PWS) is caused by a loss of paternally expressed genes in an imprinted region of chromosome 15q. Among the canonical PWS phenotypes are hyperphagic obesity, central hypogonadism, and low growth hormone (GH). Rare microdeletions in PWS patients define a 91-kb minimum...

Determination of the half-life of circulating leptin in the mouse

BACKGROUND: The adipokine hormone, leptin, is a major component of body weight homeostasis. Numerous studies have been performed administering recombinant mouse leptin as an experimental reagent; however, the half-life of circulating leptin following exogenous administration of recombinant mouse...

High unacylated ghrelin levels support the concept of anorexia in infants with prader-willi syndrome

BACKGROUND: Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder with different nutritional phases from suckling deficit with failure to thrive to early onset of obesity. Hyperghrelinemia has been described in PWS long before the development of obesity. Ghrelin is found in both...

Sexual dichotomy of gonadal function in Prader-Willi syndrome from early infancy through the fourth decade

STUDY QUESTION: At what age does the type of hypogonadism, namely hypothalamic or primary gonadal defect, become established in men and women with Prader-Willi syndrome (PWS)? SUMMARY ANSWER: The type of hypogonadism becomes established only in late adolescence and early adulthood. WHAT IS KNOWN...

Macronutrient regulation of Ghrelin and Peptide YY in Pediatric Obesity and Prader Willi Syndrome (PWS)

Abstract BACKGROUND: The roles of macronutrients and GH in the regulation of food intake in pediatric obesity and PWS are poorly understood. OBJECTIVE: We compared effects of high carbohydrate (HC) and high fat (HF) meals and GH therapy on ghrelin, insulin, PYY, and insulin sensitivity in children...

Metabolic profiling in Prader-Willi syndrome and non-syndromic obesity: sex differences and the role of growth hormone

OBJECTIVES: To identify metabolic factors controlling appetite and insulin sensitivity in PWS and assess effects of GH treatment.

Chemical identity of hypothalamic neurons engaged by leptin in reproductive control

The adipocyte-derived hormone leptin plays a critical role as a metabolic cue for the reproductive system. Conditions of low leptin levels observed in negative energy balance and loss-of-function mutations of leptin or leptin receptor genes are characterized by decreased fertility. In recent years,...

Estradiol modulates Kiss1 neuronal response to ghrelin

Ghrelin is a metabolic signal regulating energy homeostasis. Circulating ghrelin levels rise during starvation and fall after a meal, and therefore, ghrelin may function as a signal of negative energy balance. Ghrelin may also act as a modulator of reproductive physiology, as acute ghrelin...

Hyperphagia: Current concepts and future directions proceedings of the 2nd international conference on hyperphagia

Objective Hyperphagia is a central feature of inherited disorders (e.g., Prader–Willi Syndrome) in which obesity is a primary phenotypic component. Hyperphagia may also contribute to obesity as observed in the general population, thus raising the potential importance of common underlying mechanisms...

Neonatal overnutrition causes early alterations in the central response to peripheral ghrelin

Objective Excess nutrient supply and rapid weight gain during early life are risk factors for the development of obesity during adulthood. This metabolic malprogramming may be mediated by endocrine disturbances during critical periods of development. Ghrelin is a metabolic hormone secreted from the...

A critical view of the use of genetic tools to unveil neural circuits: the case of leptin action in reproduction

The remarkable development and refinement of the Cre-loxP system coupled with the nonstop production of new mouse models and virus vectors have impelled the growth of various fields of investigation. In this article, I will discuss the data collected using these genetic tools in our area of...

Longitudinal Study of Reproductive Hormones in Prader-Willi Syndrome (PWS) from Early Infancy through the Fourth Decade

Background: We previously showed in cross-sectional studies of PWS men (1) and women (2) that the etiology of hypogonadism is heterogeneous, with primary testicular failure common in PWS men and variable combinations of ovarian dysfunction and gonadotropin deficiency in women. Longitudinal studies...

CRF type 2 receptors mediate the metabolic effects of ghrelin in C2C12 cells

Objective Ghrelin is known to regulate appetite control and cellular metabolism. The corticotropin-releasing factor (CRF) family is also known to regulate energy balance. In this study, the links between ghrelin and the CRF family in C2C12 cells, a mouse myoblast cell line was investigated.

Gene-Environment Interactions Controlling Energy and Glucose Homeostasis and the Developmental Origins of Obesity

Obesity and type 2 diabetes mellitus (T2DM) often occur together and affect a growing number of individuals in both the developed and developing worlds. Both are associated with a number of other serious illnesses that lead to increased rates of mortality. There is likely a polygenic mode of...

Neonatal ghrelin programs development of hypothalamic feeding circuits

A complex neural network regulates body weight and energy balance, and dysfunction in the communication between the gut and this neural network is associated with metabolic diseases, such as obesity. The stomach-derived hormone ghrelin stimulates appetite through interactions with neurons in the...

Abnormal response to the anorexic effect of GHS-R inhibitors and exenatide in male Snord116 deletion mouse model for Prader-Willi syndrome

Prader-Willi syndrome (PWS) is a genetic disease characterized by persistent hunger and hyperphagia. The lack of the Snord116 small nucleolar RNA cluster has been identified as the major contributor to PWS symptoms. The Snord116 deletion (Snord116del) mouse model manifested a subset of PWS symptoms...

Characterization of minipuberty in infants with Prader-Willi syndrome

Background: Minipuberty describes transient activation of the hypothalamic-pituitary-gonadal axis occurring during the first few months of life. Hormone levels during minipuberty were described in only a few Prader-Willi syndrome (PWS) infant boys and have not been reported in PWS infant girls....