Dietary Fat Source Programs Distinct Plasma MicroRNA Signatures with Divergent Metabolic and Cognitive Trajectories in a Primate Model

Hepatic molecular validation was performed by Western blot and qPCR. In aged animals, dairy fat-based diet upregulated miR-132, miR-100, and miR-130a, described to be associated with insulin sensitivity and neuroprotection, while vegetable fat-based diet elevated miR-107, miR-146b, and let-7g, known as biomarkers of insulin resistance and neuroinflammation. Hepatic SOCS3 protein and pro-inflammatory cytokines were significantly elevated in vegetable fat-based diet fed animals, confirming insulin signaling impairment prior to detectable metabolic changes.

In offspring, prenatal dairy fat-based diet created persistent miRNA signatures in adulthood independent of postnatal diet, upregulating let-7f, miR-301a, and miR-502a, while prenatal vegetable fat-based diet elevated miR-204 and miR-381, known to be associated with impaired insulin signaling and neurological development. Sustained dairy fat-based diet amplified protective effects through coordinated miR-132/let-7/miR-29b upregulation.

These primate-derived miRNA signatures mirror human biomarkers of type 2 diabetes and Alzheimer's disease, establishing translational potential for early-life nutritional strategies targeting metabolic-cognitive health programming.