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Am J Physiol Endocrinol Metab. 2014 Aug 1;307(3):E335-44. doi: 10.1152/ajpendo.00075.2014. Epub 2014 Jun 17.

Heritability of fat accumulation in white adipocytes.

Author information

1
Laboratory of Endocrinology and Receptor Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
2
Laboratory of Endocrinology and Receptor Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland marving@intra.niddk.nih.gov.

Abstract

Since individual cells from freshly isolated white adipose tissue (WAT) exhibit variable levels of fat accumulation, we attempted to determine which factor(s) cause this variation. We used primary WAT cells from adult mice and the mouse 3T3-L1 cell-line of preadipocytes for these studies. Cells were labeled with BODIPY (boron-dipyrromethene) lipid probe, a marker for fat accumulation in live cells, and sorted on a fluorescence-activated cell sorter into two populations exhibiting low or high BODIPY fluorescence intensity. After more than 12 doublings as dedifferentiated cells in growth medium, the sorted populations were exposed to adipogenic medium for 7 days and analyzed for BODIPY accumulation and mRNA expression of adipogenic markers. WAT-derived cells initially sorted to have low or high BODIPY fluorescence intensity maintained a similar low or high lipid phenotype after redifferentiation. Cell surface TSH receptor expression, which is known to increase when preadipocytes are differentiated, correlated with BODIPY staining in all states. mRNA levels of Pparγ, Srebp1c, aP2, and Pref1, key regulators of adipogenesis, and leptin, Glut4, Fasn, and Tshr, markers of adipocyte differentiation, correlated with the levels of fat accumulation. Overexpression of Pparγ in 3T3-L1 cells, as expected, caused cells from low- and high-BODIPY populations to accumulate more fat. More importantly, prior to differentiation, the endogenous Pparγ promoter exhibited higher levels of acetylated histone H3, an activatory modification, in high-BODIPY- compared with low-BODIPY-derived populations. We conclude that fat accumulation is a heritable trait in WAT and that epigenetic modification on the Pparγ promoter contributes to this heritability.

KEYWORDS:

Pparγ; differentiation; epigenetics; fat; fluorescence-activated cell sorter; white adipose tissue

PMID:
24939735
PMCID:
PMC4121576
DOI:
10.1152/ajpendo.00075.2014
[Indexed for MEDLINE]
Free PMC Article
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