A5051636167- Adipose Tissue and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Sexual Differentiation and Disorders
- Diabetes and associated disorders
- Pancreatic function and diabetes
- Thyroid Disorders and Treatments
- Birth, Development, and Health
- Liver Disease Diagnosis and Treatment
- Regulation of Appetite and Obesity
- Growth Hormone and Insulin-like Growth Factors
- Metabolism, Diabetes, and Cancer
- Metabolism and Genetic Disorders
- Diet and metabolism studies
- Diabetes Management and Research
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Immune Cell Function and Interaction
- Hormonal Regulation and Hypertension
- Exercise and Physiological Responses
- Diet, Metabolism, and Disease
- Adrenal Hormones and Disorders
- Urological Disorders and Treatments
- Endoplasmic Reticulum Stress and Disease
- Chronic Kidney Disease and Diabetes
- Cardiovascular Disease and Adiposity
- Genetics and Neurodevelopmental Disorders
University Children's Hospital Zurich
2016-2025
Swiss Integrative Center for Human Health
2015-2025
University of Zurich
2015-2025
Uniwersytecki Szpital Dziecięcy
2008-2024
Children's Clinical University Hospital
2008-2024
Diabetes Australia
2011-2018
Medical University of Graz
2017
Children's Research Hospital
2015
Boston Children's Hospital
2000-2013
University Hospital of Basel
2006
WNT4, a secreted protein that suppresses male sexual differentiation, is thought to repress the biosynthesis of gonadal androgen in female mammals. An 18-year-old woman presented with primary amenorrhea and an absence müllerian-derived structures, unilateral renal agenesis, clinical signs excess--a phenotype resembling Mayer-Rokitansky-Küster-Hauser syndrome remarkably similar Wnt4-knockout mice. A genetic evaluation revealed loss-of-function mutation WNT4 gene. appears be important...
The immune system shapes body metabolism, while interactions between peripheral neurons and cells control tissue homeostasis immunity. However, whether neuroimmune orchestrate endocrine functions remains unexplored. After fasting, mice lacking type 2 innate lymphoid (ILC2s) displayed disrupted glucose homeostasis, impaired pancreatic glucagon secretion, inefficient hepatic gluconeogenesis. Additionally, intestinal ILC2s were found in the pancreas, which was dependent on their expression of...
Pten (phosphatase with tensin homology), a dual-specificity phosphatase, is negative regulator of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. regulates vast array biological functions including growth, metabolism, and longevity. Although PI3K/Akt pathway key determinant insulin-dependent increase in glucose uptake into muscle adipose cells, contribution this to whole-body homeostasis unclear. Here we show that muscle-specific deletion protected mice from insulin resistance...
The cofactor of mitochondrial dehydrogenase complexes and potent antioxidant α-lipoic acid has been shown to lower blood glucose in diabetic animals. α-Lipoic enhances uptake GLUT1 GLUT4 translocation 3T3-L1 adipocytes L6 myotubes, mimicking insulin action. In both cell types, insulin-stimulated is reduced by inhibitors p38 mitogen-activated protein kinase (MAPK). Here we explore the effect on MAPK, phosphatidylinositol (PI) 3-kinase, Akt1 myotubes. (2.5 mmol/l) increased PI 3-kinase...
The pathways leading to female sexual determination in mammals are incompletely defined. Loss-of-function mutations the WNT4 gene appear cause developmental abnormalities of differentiation women and mice. We recruited six patients with different degrees Müllerian abnormalities, or without renal aberrations a normal 46,XX karyotype. A clear androgen excess was found only one patient. This 19-year-old woman affected by primary amenorrhoea, absence ducts derivatives, clinical (acne hirsutism)...
OBJECTIVE The “portal hypothesis” proposes that the liver is directly exposed to free fatty acids and cytokines increasingly released from visceral fat tissue into portal vein of obese subjects, thus rendering accumulation particularly hazardous for development hepatic insulin resistance type 2 diabetes. In present study, we used a transplantation paradigm (artificially) increase intra-abdominal mass test hypothesis venous drainage determines its impact on glucose homeostasis. RESEARCH...
Müllerian duct development depends on gene and hormone interactions. Female Wnt4-knockout mice lack müllerian ducts are virilized due to the inappropriate expression of enzymes required for androgen production (normally repressed in female ovary). The WNT4 mutation was recently reported be associated with failure formation virilization two 46, XX women.This collaborative work designed determine whether could identified a group adolescent girls Mayer-Rokitansky-Küster-Hauser syndrome.We...
Adipose tissue inflammation is linked to the pathogenesis of insulin resistance. In addition exerting death-promoting effects, death receptor Fas (also known as CD95) can activate inflammatory pathways in several cell lines and tissues, although little about metabolic consequence activation adipose tissue. We therefore sought investigate contribution adipocytes obesity-associated dysregulation. expression was markedly increased common genetic diet-induced mouse models obesity resistance,...
The inflammasome has been recently implicated in obesity-associated dys-metabolism. However, of its products, the specific role IL-1β was clinically demonstrated to mediate only pancreatic beta-cell demise, and mice mainly intra-hepatic manifestations obesity. Yet, it remains largely unknown if IL-1β, a cytokine believed function locally, could regulate dysfunctional inter-organ crosstalk Here we show that High-fat-fed (HFF) exhibited preferential increase portal compared systemic blood....
Monocarboxylate transporter 8 (MCT8) is a thyroid hormone-specific cell membrane transporter. MCT8 deficiency causes severe psychomotor retardation and abnormal tests. The great majority of affected children cannot walk or talk, all have elevated serum T3 levels, causing peripheral tissue hypermetabolism inability to maintain weight. Treatment with hormone ineffective. In Mct8-deficient mice, the analog, diiodothyropropionic acid (DITPA), does not require enter tissues could be an effective...
Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility. There are no intact extensively hydrolyzed formulas.To test hypothesis that weaning an formula decreases cumulative incidence young children.An international double-blind randomized clinical trial 2159 infants human leukocyte antigen-conferred susceptibility and a first-degree relative recruited from May 2002 January 2007 78 study centers 15 countries; 1081...
Objective Congenital hypogonadotropic hypogonadism (CHH) and constitutional delay of growth puberty (CDGP) represent rare common forms GnRH deficiency, respectively. Both CDGP CHH present with delayed puberty, the distinction between these two entities during early adolescence is challenging. More than 30 genes have been implicated in CHH, while genetic basis poorly understood. Design We characterized compared architectures CDGP, to test hypothesis a shared disorders. Methods Exome...
Key points A ketogenic diet is known to lead weight loss and considered metabolically healthy; however there are conflicting reports on its effect hepatic insulin sensitivity. KD fed animals appear healthy in the fasted state after 3 days of dietary challenge, whereas obesogenic high‐fat (HFD) show elevated levels. glucose challenge reveals that both HFD intolerant. Glucose intolerance correlates with increased lipid oxidation lower respiratory exchange ratio (RER); however, all respond...
Abstract Predicting and quantifying phenotypic consequences of genetic variants in rare disorders is a major challenge, particularly pertinent for ‘actionable’ genes such as thyroid hormone transporter MCT8 (encoded by the X-linked SLC16A2 gene), where loss-of-function (LoF) cause neurodevelopmental (treatable) metabolic disorder males. The combination deep phenotyping data with functional computational tests outcomes population cohorts, enabled us to: (i) identify aetiology divergent...
Abstract Background 46,XY gonadal dysgenesis is classified as complete (CGD) or partial (PGD) subtypes. The phenotype of PGD and the long-term outcome not clearly defined. Objective To evaluate clinical features pubertal in a large cohort, using CGD comparator for diagnostic clarity. Methods Patients with GD were identified from I-DSD Registry data on phenotype, genetics, biochemistry, histology development collated three categories; (n=100), assigned female (PGDf, n=107) male (PGDm, n=103)...