Adipose tissue development is tightly regulated by altering gene expression. MicroRNAs are strong posttranscriptional regulators of mammalian differentiation. We hypothesized that microRNAs might influence human adipogenesis by targeting specific adipogenic factors. We identified microRNAs that showed varying abundance during the differentiation of human preadipocytes into adipocytes. Among them, miR-130 strongly affected adipocyte differentiation, as overexpressing miR-130 impaired adipogenesis and reducing miR-130 enhanced adipogenesis. A key effector of miR-130 actions was the protein peroxisome proliferator-activated receptor ␥ (PPAR␥), a major regulator of adipogenesis. Interestingly, miR-130 potently repressed PPAR␥ expression by targeting both the PPAR␥ mRNA coding and 3 untranslated regions. Adipose tissue from obese women contained significantly lower miR-130 and higher PPAR␥ mRNA levels than that from nonobese women. Our findings reveal that miR-130 reduces adipogenesis by repressing PPAR␥ biosynthesis and suggest that perturbations in this regulation is linked to human obesity.

Inflammation is a common component of acute injuries of the central nervous system (CNS) and degenerative disorders such as Alzheimer’s disease. Glial cells play important roles in local CNS inflammation, and an understanding of the roles for microRNAs in glial reactivity in injury and disease settings may therefore enable novel therapeutic interventions. Here we show that the miR-181 family is developmentally regulated and present in high amounts in astrocytes compared to neurons. Over-expression of miR-181c in cultured astrocytes results in increased cell death when exposed to lipopolysaccharide (LPS). We show that miR-181 expression is altered in brain cells in vivo in response to LPS, a model of inflammation, in both wild-type mice and transgenic mice lacking both receptors for the inflammatory cytokine TNF-α. Knockdown of miR-181 enhanced LPS-induced production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-8) and HMGB1, while over-expression of miR-181 resulted in a significant increase in the expression of the anti-inflammatory cytokine IL-10. To assess the effects of miR-181 on the astrocyte transcriptome, we performed gene array and pathway analysis on astrocytes with reduced levels of miR-181b/c. To examine the pool of potential miR-181 targets, we employed a biotin pull-down of miR-181c and microarray analysis. We validated both MeCP2 and XIAP mRNAs as targets of miR-181. These findings suggest that miR-181 plays important roles in the response of astrocytes to inflammatory settings. Further understanding of the role of miR-181 in inflammatory events and CNS injury could lead to novel therapies for CNS disorders with an inflammatory component.

Telomeres, ribonucleoprotein complexes that cap eukaryotic chromosomes, typically shorten in leukocytes with aging. Aging is a primary risk factor for neurodegenerative disease (ND), and a common assumption has arisen that leukocyte telomere length (LTL) can serve as a predictor of neurological disease. However, the evidence for shorter LTL in Alzheimer’s and Parkinson’s patients is inconsistent. The diverse causes of telomere shortening may explain variability in LTL between studies and individuals. Additional research is needed to determine whether neuronal and glial telomeres shorten during aging and in neurodegenerative disorders, if and how LTL is related to brain cell telomere shortening, and whether telomere shortening plays a causal role in or exacerbates neurological disorders.