A Cross-Species Atlas of the Dorsal Vagal Complex Reveals Neural Mediators of Cagrilintide's Effects on Energy Balance.

Amylin analogs, including potential anti-obesity therapies like cagrilintide, act on neurons in the brainstem dorsal vagal complex (DVC) that express calcitonin receptors (CALCR). These receptors, often combined with receptor activity-modifying proteins (RAMPs), mediate the suppression of food intake and body weight. To understand the molecular and neural mechanisms of cagrilintide action, we used single-nucleus RNA sequencing to define 89 cell populations across the rat, mouse, and non-human primate caudal brainstem.

Maternal Western Diet Programmes Bile Acid Dysregulation and Hepatic Fibrosis in Fetal and Juvenile Macaques.

Background And Aims: Maternal obesity increases the risk of the paediatric form of metabolic dysfunction-associated steatotic liver disease (MASLD), affecting up to 30% of youth, but the developmental origins remain poorly understood.

Methods: Using a Japanese macaque model, we investigated the impact of maternal Western-style diet (mWSD) or chow diet followed by postweaning WSD (pwWSD) or chow diet focusing on bile acid (BA) homeostasis and hepatic fibrosis in livers from third-trimester fetuses and 3-year-old juvenile offspring.

Results: Juveniles exposed to mWSD had increased hepatic collagen I/III content and stellate cell activation in portal regions.

Preparation of Frozen Non-Human Primate Fetal Islets for Combined Single Nuclei RNA-Sequencing and ATAC-Sequencing, and Bulk Metabolomics.

One challenge in studies using tissue collected from multiple cohorts is avoiding batch effects when preparing for large-scale multi-omic experiments, such as combined single-cell RNA sequencing and metabolomics. The method in the current study utilizes flash-frozen pancreatic islets from fetal non-human primates collected over a span of two years for input into single-nucleus RNA sequencing and ATAC sequencing assays. The cytosolic fraction generated during nuclear extraction was retained for downstream capillary electrophoresis-mass spectrometry and subsequent metabolite quantification.

Effect of metabolic status on response to SIV infection and antiretroviral therapy in nonhuman primates.

Current antiretroviral therapy (ART) regimens efficiently limit HIV replication, thereby improving the life expectancy of people living with HIV; however, they also cause metabolic side effects. The ongoing obesity epidemic has resulted in more people with metabolic comorbidities at the time of HIV infection, yet the effect of preexisting metabolic dysregulation on infection sequelae and response to ART is unclear. Here, to investigate the impact of preexisting obesity and insulin resistance on acute infection and subsequent long-term ART, we infected a cohort of lean and obese adult male macaques with SIV and administered ART.