A Multimodal Rat Brain Atlas and Whole-Brain Imaging Pipeline for Mapping Satiety Pathways and Anti-Obesity Drug Effects
Background & aim: Central regulation of appetite and satiety engages neuronal populations distributed across the brain. The identification of novel drug targets, development of anti-obesity therapeutics, and validation of their mode of action benefit from whole-brain imaging. Light-sheet fluorescence…
Survodutide acts through circumventricular organs in the brain and activates neuronal regions associated with appetite regulation
Abstract: Survodutide is a novel GCG/GLP-1 receptor (GCGR/GLP-1R) dual agonist in clinical development for people with obesity and people with metabolic dysfunction-associated steatohepatitis (MASH). Preclinically, survodutide demonstrated body weight lowering efficacy through decreased energy intake and increased energy expenditure. Here,…
Generation and characterisation of a humanised GLP-1 receptor mouse model for translational drug development
Background: Injectable peptide-based glucagon-like peptide-1 receptor (GLP1R) agonists (GLP1RAs) are effective treatments for obesity and diabetes but are limited by patient compliance and scalability challenges. In contrast, non-peptide small-molecule GLP1RAs offer the advantage of oral delivery but are relatively inactive…
GUB-UCN2 as Monotherapy and in Combination with Semaglutide Improves Body Composition and Metabolic Outcomes in Aged Diet-Induced Obese Rats
Background & aim: Glucagon-like peptide-1 receptor agonists, such as semaglutide, induce substantial weight loss but may adversely affect muscle mass. This is of particular concern in older adults with obesity, who are vulnerable to sarcopenia. Accordingly, obesity treatments should be…
Elucidating the potential benefit of pump-delivered subcutaneous GLP-1R agonist: an exploratory study in the diet-induced obese mouse
Background & aim: Subcutaneous pump delivery of the GLP1-receptor-agonist exenatide reduced body weight and improved glycemia in the DIO mouse. Basal-bolus administration conferred advantage over basal alone. This mode of incretin-based therapy offers an alternative to conventional intermittent dosing and…
Deep learning-enhanced 3D imaging unveils semaglutide impact on cardiac fibrosis
Background & aim: Myocardial fibrosis (MF), a hallmark of structural cardiac remodelling, drives disease progression across most forms of heart failure and plays a central role in heart failure with preserved ejection fraction (HFpEF). Despite its clinical relevance, effective treatments…
Renal transcriptomic profiling reveals beneficial effects of semaglutide and lisinopril in advanced diabetic kidney disease
Background & aim: Obesity, hyperglycemia and hypertension are critical risk factors for development of diabetic kidney disease (DKD). While emerging evidence suggests that glucagon-like peptide-1 receptor (GLP1R) agonists improve cardiovascular and renal outcomes in type 2 diabetes patients, their mode…