{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE336nnn/GSE336440/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Microcebus murinus"],"gds_type":["Non-coding RNA profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE336440"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Dietary Fat Source Programs Distinct Plasma MicroRNA Signatures with Divergent Metabolic and Cognitive Trajectories in a Primate Model","description":"Dietary fat composition profoundly influences metabolic and cognitive health, yet the molecular mechanisms underlying these effects, particularly during critical developmental windows, remain incompletely understood. This study aimed to determine whether dairy fat-based diet versus vegetable fat-based diet induces distinct plasma miRNA signatures with divergent metabolic and neuroprotective consequences in both aged animals and developmentally programmed offspring. Using the gray mouse lemur (Microcebus murinus), a non-human primate model of aging and neurodegeneration, aged females and offspring born to mothers fed isocaloric dairy fat-based (D) or vegetable fat-base (V) diets were studied. Plasma miRNA profiling was performed by small RNA sequencing. Four offspring groups (DD, DV, VD, VV) were examined to disentangle prenatal and postnatal dietary fat effects. 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.","dates":{"publication":"2026/06/27"},"accession":"GSE336440","cross_references":{"GSM":["GSM9835169","GSM9835167","GSM9835161","GSM9835162","GSM9835173","GSM9835171","GSM9835165","GSM9835164"],"GPL":["37143"],"GSE":["336440"],"taxon":["Microcebus murinus"]}}