Abstract
We tested the hypothesis that prenatal administration of PPARα agonist clofibrate may permanently increase browning capacity of developing white adipose tissue (WAT). Pregnant C57BL/6J mice were fed a basal diet, without (C) or with 0.5% clofibrate (CF, a PPARα agonist) throughout pregnancy. After parturition, only male offspring were used; all suckled their mothers (who were eating the C diet) and after weaning, they ate a standard chow diet for 4 wk, followed by a high-fat diet (HFD) for 5 wk. Administration of CF up-regulated serum concentrations and hepatic expression of FGF21 in fetuses, with a return to basal levels after CF withdrawal. At postnatal day 84 (P84), CF-offspring had significantly higher expression of thermogenic genes (Ucp1, Cidea, Ppara Ppargc1a, Cpt1b) and UCP1 protein levels in response to HFD in inguinal fat, but not in retroperitoneal (combined with perirenal) or epididymal fat. Based on UCP1 levels in inguinal fat on P7, P14, and P21, appearance of the transient brown-adipocyte phenotype seemed to be hastened by CF exposure. We concluded that giving CF to pregnant mice programmed greater HFD-induced WAT browning in subcutaneous, but not in visceral fat, in their male offspring at adulthood.
Highlights
White and brown are 2 distinct adipose tissues for storage of excess energy and thermogenesis, respectively
In addition to traditional white and brown adipocytes, a third type of adipocyte, i.e. brown-in-white or beige cells, that emerge within white adipose tissue (WAT) are regarded as a plastic response to an energy surplus [1]
Beige/brite adipocytes are inducible, multilocular, uncoupling protein 1 (UCP1)-positive, and thermogenic [2]. The relevance of this issue to anti-obesity was highlighted by 18 fluorodeoxyglucose-positron emission tomography detection of brown adipose tissue (BAT) in supraclavicular and neck regions of adult humans; its activity was inversely correlated with BMI [3,4,5]
Summary
White and brown are 2 distinct adipose tissues for storage of excess energy and thermogenesis, respectively. In addition to traditional white and brown adipocytes, a third type of adipocyte, i.e. brown-in-white (brite) or beige cells, that emerge within white adipose tissue (WAT) are regarded as a plastic response to an energy surplus [1]. Beige/brite adipocytes are inducible, multilocular, UCP1-positive, and thermogenic (produce and dissipate heat) [2]. The relevance of this issue to anti-obesity was highlighted by 18 fluorodeoxyglucose-positron emission tomography detection of brown adipose tissue (BAT) in supraclavicular and neck regions of adult humans; its activity was inversely correlated with BMI [3,4,5]. Human BAT had molecular signatures that resembled murine brite cells rather than classical brown adipocytes present in interscapular BAT [2].
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