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|Type:||Artigo de periódico|
|Title:||Hyperlipidemic mice present enhanced catabolism and higher mitochondrial ATP-sensitive K+ channel activity|
|Abstract:||Background & Aims: Changes in mitochondrial energy metabolism promoted by uncoupling proteins (UCPs) are often found in metabolic disorders. We have recently shown that hypertriglyceridemic (HTG) mice present higher mitochondrial resting respiration unrelated to UCPs. Here, we disclose the underlying mechanism and consequences, in tissue and whole body metabolism, of this mitochondrial response to hyperlipidemia. Methods: Oxidative metabolism and its response to mitochondrial adenosine rriphosphate (ATP)-sensitive K+ channel (mitoK(ATP)) agonists and antagonists were measured in isolated mitochondria, livers, and mice. Results: Mitochondria isolated from the livers of HTG mice presented enhanced respiratory rates compared with those from wild-type mice. Changes in oxygen consumption were sensitive to adenosine triphosphate (ATP), diazoxide, and 5-hydroxydecanoate, indicating they are attributable to mitochondrial ATP-sensitive K+ channel (mitoK(ATP)) activity. Indeed, mitochondria from HTG mice presented enhanced swelling in the presence of K+ ions, sensitive to mitoKATpagonists and antagonists. Furthermore, mitochondrial binding to fluorescent glibenclamide indicates that HTG mice expressed higher quantities of mitoKATp. The higher content and activity of liver mitoKATpresulted in a faster metabolic state, as evidenced by increased liver oxygen consumption and higher body CO2 release and temperature in these mice. In agreement with higher metabolic rates, food ingestion was significantly larger in HTG mice, without enhanced weight gain. Conclusions: These results show that primary hyperlipidernia leads to an elevation in liver mitoK(ATp)activity, which may represent a regulated adaptation to oxidize excess fatty acids in HTG mice. Furthermore, our data indicate that mitoKATP, in addition to UCPs, may be involved in the control of energy metabolism and body weight.|
|Editor:||W B Saunders Co-elsevier Inc|
|Appears in Collections:||Artigos e Materiais de Revistas Científicas - Unicamp|
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