Endocrine Abstracts

Introduction: Despite a plethora of suggested targets and pathways, the mechanism of anti-hyperglycaemic metformin action is still unknown. The present study critically re-analysed protocols broadly applied in preclinical rodent studies.Methods: Obese male C57BL/6J mice on high fat diet were treated with metformin in the form of a single dose, daily intraperitoneal injections, admixture to drinking water, or continuous infusion via intraperitoneal minipu...

Introduction: Mountain dwellers show a lower prevalence of diabetes, which among countless other factors could be due to lower partial oxygen pressure at high altitude. The present study was to investigate in an experimental setting, if and how reduced oxygen availability affects blood glucose.Methods: Male obese mice on high fat diet were continuously maintained under a normobaric hypoxic atmosphere (10% oxygen) for three months. To exclude indirect eff...

Introduction: Transmission electron microscopy (TEM) is the main tool for studying the ultrastructural properties of metabolically diseased tissue. For impactful micrographs as well as for interpretation of TEM specimens, the integrity of cellular components is crucial. Elution of substances is a major problem in TEM preparation with no universal solution found so far. Investigating fatty liver disease in a rat model, an important factor is the depiction of undamaged lipid dro...

Background: Leptin reduces hepatic lipid content in lipodystrophic and overweight, relatively hypoleptinemic NAFLD patients. However, the underlying mechanism is unknown. In rodents, the anti-steatotic action of leptin is mediated by an increase in VLDL secretion and depends on an intact vagal innervation of the liver.Methods: In this randomized, placebo-controlled, crossover trial, we study the effects of a single metreleptin injection (0.1 mg/kg body w...

Introduction: Non-alcoholic fatty liver disease (NAFLD) is a systemic, metabolic condition associated with increased morbidity and mortality. Defined by an increase in hepatic lipid content (HCL), NAFLD develops in consequence of lipid oversupply and/or a diminished disposal of hepatic lipids. The latter may include an impaired export of triglycerides (TG) via the secretion of very-low density lipoprotein1 (VLDL1) particles, an important mechanism of the liver to protect itsel...

Objective: Treatment with metreleptin ameliorates hepatic steatosis in patients with lipodystrophy. The anti-steatotic effect of metreleptin is partially independent of its anorexic action, which suggests a direct effect of metreleptin on hepatic lipid metabolism. However, this mechanism is unknown. Based on previous findings in rodents, we hypothesized that metreleptin reduces hepatic lipid content by stimulating very-low density lipoprotein triglyceride (VLDL1-TG) secretion,...