Super-Obese Patient-Derived iPSC Hypothalamic Neurons Exhibit Obesogenic Signatures and Hormone Responses.

ABSTRACT: The hypothalamus contains neurons that integrate hunger and satiety endocrine signals from the periphery and are implicated in the pathophysiology of obesity. The limited availability of human hypothalamic neurons hampers our understanding of obesity disease mechanisms. To address this, we generated human induced pluripotent stem cells (hiPSCs) from multiple normal body mass index (BMI; BMI ≤ 25) subjects and super-obese (OBS) donors (BMI ≥ 50) with polygenic coding variants in obesity-associated genes. We developed a method to reliably differentiate hiPSCs into hypothalamic-like neurons (iHTNs) capable of secreting orexigenic and anorexigenic neuropeptides. Transcriptomic profiling revealed that, although iHTNs maintain a fetal identity, they respond appropriately to metabolic hormones gh

SUBMITTER: Rajamani U 

PROVIDER: S-EPMC6398951 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature