Oleoyl-estrone inhibits lipogenic but maintains thermogenic gene expression of brown adipose tissue in overweight rats
Résumé
We intended to determine how brown adipose tissue (BAT) maintained thermogenesis under treatment with oleoyl-estrone (OE), a powerful slimming hormone that sheds off body lipid but maintaining the metabolic rate. Overweight male rats were subjected to daily gavages of 10 nmol/g OE or vehicle (controls) for 10 days. A pair-fed vehicle-receiving group (PF) was used to discount the effects attributable to energy availability limitation. Interscapular BAT weight, lipid, DNA, mRNA and the RT-PCR expression of lipid and energy metabolism genes for enzymes and regulatory proteins were measured. BAT weight and lipid decreased in OE and PF; the latter showing a marked reduction of tissue mRNA. Maintenance of perilipin gene expression in PF and OE rats despite the loss of lipid suggests the preservation of the vacuolar interactive surface, a critical factor for thermogenic responsiveness. OE (and to a lower extent PF) maintained the expression of genes controlling lipolysis and fatty acid oxidation, but markedly decreased those of lipogenic and acyl-glycerol synthesis. OE did not affect UCP1 (decreased in PF), β3 adrenergic receptors or hormone-sensitive lipase gene mRNAs , which may translate in maintaining a full thermogenic system potential. OE rats were able to maintain a less energetically stressed BAT (probably with the concourse of glucose utilization) than PF animals. These changes were not paralleled in PF rats, which lower thermogenesis and glucose preservation resulted in a heavier toll on internal fat stores. Thus, the mechanism of action of OE is more complex and tissue-specific than previously assumed.
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