GCG and obesity due to melanocortin 4 receptor deficiency: As proof-of-concept, we show that alginate-encapsulated engineered cells implanted in C3H/HeJ male mice can translate circadian inputs or clinically licensed MTNR1A agonists into regulated GLP-1 expression as a therapeutic output exclusively secreted during nighttime, highlighting potential as an experimental cell therapy for obesity-dependent type-2 diabetes.