Region-specific transcriptomic responses to obesity and diabetes in macaque hypothalamus.
Cell Metab
; 36(2): 438-453.e6, 2024 02 06.
Article
en En
| MEDLINE
| ID: mdl-38325338
ABSTRACT
The hypothalamus plays a crucial role in the progression of obesity and diabetes; however, its structural complexity and cellular heterogeneity impede targeted treatments. Here, we profiled the single-cell and spatial transcriptome of the hypothalamus in obese and sporadic type 2 diabetic macaques, revealing primate-specific distributions of clusters and genes as well as spatial region, cell-type-, and gene-feature-specific changes. The infundibular (INF) and paraventricular nuclei (PVN) are most susceptible to metabolic disruption, with the PVN being more sensitive to diabetes. In the INF, obesity results in reduced synaptic plasticity and energy sensing capability, whereas diabetes involves molecular reprogramming associated with impaired tanycytic barriers, activated microglia, and neuronal inflammatory response. In the PVN, cellular metabolism and neural activity are suppressed in diabetic macaques. Spatial transcriptomic data reveal microglia's preference for the parenchyma over the third ventricle in diabetes. Our findings provide a comprehensive view of molecular changes associated with obesity and diabetes.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Núcleo Hipotalámico Paraventricular
/
Diabetes Mellitus
Límite:
Animals
Idioma:
En
Revista:
Cell Metab
Asunto de la revista:
METABOLISMO
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos