期刊
CELL DEATH AND DIFFERENTIATION
卷 19, 期 6, 页码 1003-1012出版社
SPRINGERNATURE
DOI: 10.1038/cdd.2011.183
关键词
nutritional programming; maternal diet; translational control; microRNA; miR-483; GDF3
资金
- BBSRC [BB/F-15364/1, BB/F-14279/1]
- MRC Centre for Obesity and Related Metabolic Diseases (MRC-CORD)
- Biotechnology and Biological Sciences Research Council [BB/F015364/1, BB/F019017/1, BB/F011806/1, BB/F019017/2, BB/B500915/1, BB/F014279/2, BB/F014279/1] Funding Source: researchfish
- British Heart Foundation [FS/09/029/27902] Funding Source: researchfish
- Medical Research Council [MC_UP_A600_1023, G0600717B, MC_UP_A600_1024] Funding Source: researchfish
- BBSRC [BB/F014279/1, BB/F015364/1, BB/F019017/1, BB/F011806/1, BB/F014279/2, BB/F019017/2] Funding Source: UKRI
- MRC [MC_UP_A600_1023, MC_UP_A600_1024] Funding Source: UKRI
Nutrition during early mammalian development permanently influences health of the adult, including increasing the risk of type 2 diabetes and coronary heart disease. However, the molecular mechanisms underlying such programming are poorly defined. Here we demonstrate that programmed changes in miRNA expression link early-life nutrition to long-term health. Specifically, we show that miR-483-3p is upregulated in adipose tissue from low-birth-weight adult humans and prediabetic adult rats exposed to suboptimal nutrition in early life. We demonstrate that manipulation of miR-483-3p levels in vitro substantially modulates the capacity of adipocytes to differentiate and store lipids. We show that some of these effects are mediated by translational repression of growth/differentiation factor-3, a target of miR-483-3p. We propose that increased miR-483-3p expression in vivo, programmed by early-life nutrition, limits storage of lipids in adipose tissue, causing lipotoxicity and insulin resistance and thus increasing susceptibility to metabolic disease. Cell Death and Differentiation (2012) 19, 1003-1012; doi:10.1038/cdd.2011.183; published online 6 January 2012
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