Leptin is a hormone secreted by adipocytes that plays a pivotal role in regulating food intake, energy expenditure and neuroendocrine function. Leptin stimulates the oxidation of fatty acids and the uptake of glucose, and prevents the accumulation of lipids in nonadipose tissues, which can lead to functional impairments known as "lipotoxicity". The signalling pathways that mediate the metabolic effects of leptin remain undefined. The 5'-AMP-activated protein kinase (AMPK) potently stimulates fatty-acid oxidation in muscle by inhibiting the activity of acetyl coenzyme A carboxylase (ACC). AMPK is a heterotrimeric enzyme that is conserved from yeast to humans and functions as a 'fuel gauge' to monitor the status of cellular energy. Here we show that leptin selectively stimulates phosphorylation and activation of the alpha2 catalytic subunit of AMPK (alpha2 AMPK) in skeletal muscle, thus establishing a previously unknown signalling pathway for leptin. Early activation of AMPK occurs by leptin acting directly on muscle, whereas later activation depends on leptin functioning through the hypothalamic-sympathetic nervous system axis. In parallel with its activation of AMPK, leptin suppresses the activity of ACC, thereby stimulating the oxidation of fatty acids in muscle. Blocking AMPK activation inhibits the phosphorylation of ACC stimulated by leptin. Our data identify AMPK as a principal mediator of the effects of leptin on fatty-acid metabolism in muscle.

Radiolabeled FAPI (fibroblast activation protein inhibitors) recently gained attention as widely applicable imaging and potential therapeutic compounds targeting CAF (cancer-associated fibroblasts) or DAF (disease-associated fibroblasts in benign disorders). Moreover, the use of FAPI has distinct advantages compared to FDG (e.g., increased sensitivity in regions with high glucose metabolism, no need for fasting, and rapid imaging). In this study, we wanted to evaluate the radiochemical synthesis and the clinical properties of the new CAF-targeting tracer [68Ga]Ga-DATA5m.SA.FAPi. The compound consists of a (radio)chemically easy to use hybrid chelate DATA.SA, which can be labeled at low temperatures, making it an interesting molecule for ‘instant kit-type’ labeling, and a squaric acid moiety that provides distinct advantages for synthesis and radiolabeling. Our work demonstrates that automatic synthesis of the FAP inhibitor [68Ga]Ga-DATA5m.SA.FAPi is feasible and reproducible, providing convenient access to this new hybrid chelator-based tracer. Our studies demonstrated the diagnostic usability of [68Ga]Ga-DATA5m.SA.FAPi for the unambiguous detection of cancer-associated fibroblasts of various carcinomas and their metastases (NSCLC, liposarcoma, parotid tumors, prostate cancer, and pancreas adenocarcinoma), while physiological uptake in brain, liver, intestine, bone, and lungs was very low.

Innerhalb eines vom BMWi (Bundesministerium für Wirtschaft und Technologie) geförderten ZIM‐Projektes (Zentrales Innovationsprogramm Mittelstand) wurden am Institut für Baustoffe, Massivbau und Brandschutz (iBMB) der Technischen Universität Braunschweig in Kooperation mit der Firma Europoles GmbH & Co. KG sowie dem Stahlwerk Annahütte experimentelle und theoretische Untersuchungen zum Last‐Verformungsverhalten von Schleuderbetonstützen aus hochfester Betonstahlbewehrung und ultrahochfestem Beton durchgeführt. Des Weiteren wurden das Kurz‐ und Langzeit‐Materialverhalten der eingesetzten Hochleistungswerkstoffe untersucht.Spun concrete columns made of high strength reinforcement and ultra‐high performance concreteWithin a ZIM (Zentrales Innovationsprogramm Mittelstand) research project, founded by the BMWi (Bundesministerium für Wirtschaft und Technologie), the load‐deformation behavior of spun concrete columns made of high strength reinforcement and ultra‐high performance concrete was investigated at the iBMB of the Technische Universität Braunschweig in cooperation with the companies Europoles GmbH & Co. KG and Stahlwerk Annahütte. Furthermore, the short‐ and long‐term material behavior of the used high performance materials was analyzed.

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