Although commonly associated with obesity, non-alcoholic fatty liver disease (NAFLD) is also present in the lean population representing a unique disease phenotype. Affecting 25% of the world's population, NAFLD is associated with increased mortality especially when progressed to non-alcoholic steatohepatitis (NASH). However, no approved pharmacological treatments exist. Current research focuses mainly on NASH associated with obesity, leaving the effectiveness of promising treatments in lean NASH virtually unknown. This study therefore aimed to evaluate the effect of liraglutide (glucagon-like peptide 1 analogue) and dietary intervention, alone and in combination, in guinea pigs with non-obese NASH. After 20 weeks of high-fat feeding (20% fat, 15% sucrose, 0.35% cholesterol), 40 female guinea pigs were block-randomized based on weight into four groups receiving one of four treatments for 4 weeks: continued high-fat diet (HF, control), high-fat diet and liraglutide treatment (HFL), chow diet (4% fat, 0% sucrose, 0% cholesterol; HFC) or chow diet and liraglutide treatment (HFCL). High-fat feeding induced NASH with severe fibrosis. Liraglutide decreased inflammation (p < 0.05) and hepatocyte ballooning (p < 0.05), while increasing hepatic α-tocopherol (p = 0.0154). Dietary intervention did not improve liver histopathology significantly, but decreased liver weight (p = 0.004), plasma total cholesterol (p = 0.0175), LDL-cholesterol (p = 0.0063), VLDL-cholesterol (p = 0.0034), hepatic cholesterol (p < 0.0001) and increased hepatic vitamin C (p = 0.0099). Combined liraglutide and dietary intervention induced a rapid weight loss, necessitating periodical liraglutide dose adjustment/discontinuation, limiting the strength of the findings from this group. Collectively, this pre-clinical study supports the beneficial effect of liraglutide on NASH and extends this notion to lean NASH.

Ceruloplasmin (Cp) is a multicopper oxidase with ferroxidase properties being of importance to the mobilisation and export of iron from cells and its ability to bind copper. In ageing humans, Cp deficiency is known to result in aceruloplasminemia, which among other is characterised by neurological symptoms. To obtain novel information about the functions of Cp in the central nervous system (CNS) we compared the brain proteome in forebrains from asymptomatic 4‐6‐month‐old Cp‐deficient (B6N(Cg)‐Cptm1b(KOMP)Wtsi/J) and wild‐type mice. Of more than 5600 quantified proteins, 23 proteins, were regulated, whereas more than 1200 proteins had regulated post‐translational modifications (PTMs). The genes of the regulated proteins, glycoproteins and phosphoproteins appeared mostly to be located to neurons and oligodendrocyte precursor cells. Cp deficiency especially affected the function of proteins involved in the extension of neuronal projections, synaptic signalling and cellular mRNA processing and affected the expression of proteins involved in neurodegenerative disease and diabetes. Iron concentration and transferrin saturation were reduced in the blood of even younger, 3‐ to 5‐month‐old, Cp‐deficient mice. Iron act as cofactor in many enzymatic processes and reactions. Changes in iron availability and oxidation as consequence of Cp deficiency could therefore affect the synthesis of proteins and lipids. This proteomic characterisation is to our knowledge the first to document the changes taking place in the CNS‐proteome and its phosphorylation and glycosylation state in Cp‐deficient mice.

Skull surgery, also known as craniectomy, is done to treat trauma or brain diseases and may require the use of an implant to reestablish skull integrity. This study investigates the performance of 3D printed bone implants in a mouse model of craniectomy with the aim of making biodegradable porous implants that can ultimately be fitted to a patient's anatomy. A nonpolymeric thermoplastic bioink composed of fatty acids and β‐tricalcium phosphate was used to 3D print the skull implants. Some of these were sintered to yield pure β‐tricalcium phosphate implants. The performance of nonsintered and sintered implants was then compared in two semi‐quantitative murine calvarial defect models using computed tomography, histology, and luciferase activity. Both types of implants were biocompatible, but only sintered implants promoted defect healing, with osseointegration to adjacent bone and the formation of new bone and bone marrow tissue in the implant pores. Luciferase scanning and histology showed that mesenchymal stem cells seeded onto the implants engraft and proliferate on the implants after implantation and contribute to forming bone. The experiments indicate that fatty acid‐based 3D printing enables the creation of biocompatible and bone‐forming β‐tricalcium phosphate implants.

In anaesthetic practice the risk of hypoxia and arterial blood gas disturbances is evident, as most anaesthetic regimens depress the respiratory function. Hypoxia may be extended during recovery, and for this reason we wished to investigate if oxygen supply during a one hour post-operative period reduced the development of hypoxia and respiratory acidosis in rats anaesthetized with fentanyl/fluanisone and midazolam. Twelve Sprague Dawley rats underwent surgery and were divided in two groups, breathing either 100% oxygen or atmospheric air during a post-operative period. The peripheral blood oxygen saturation and arterial acid-base status were analyzed for differences between the two groups. We found that oxygen supply after surgery prevented hypoxia but did not result in a significant difference in the blood acid-base status. All rats developed respiratory acidosis, which could not be reversed by supplemental oxygen supply. We concluded that oxygen supply improved oxygen saturation and avoided hypoxia but did not have an influence on the acid-base status.