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Hyperlipidemic mice present enhanced catabolism and higher mitochondrial ATP-sensitive K+ channel activity
- Source :
- Gastroenterology. 131(4)
- Publication Year :
- 2006
-
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 triphosphate (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 mitoK ATP agonists and antagonists. Furthermore, mitochondrial binding to fluorescent glibenclamide indicates that HTG mice expressed higher quantities of mitoK ATP . The higher content and activity of liver mitoK ATP resulted in a faster metabolic state, as evidenced by increased liver oxygen consumption and higher body co 2 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 hyperlipidemia 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 mitoK ATP , in addition to UCPs, may be involved in the control of energy metabolism and body weight.
- Subjects :
- medicine.medical_specialty
Potassium Channels
Cell Respiration
Hyperlipidemias
Mice, Transgenic
Mitochondria, Liver
Mitochondrion
Biology
Body Temperature
chemistry.chemical_compound
Eating
Mice
Internal medicine
Respiration
medicine
Diazoxide
Uncoupling protein
Animals
Humans
Apolipoprotein C-III
Hepatology
Catabolism
Fatty Acids
Gastroenterology
Metabolism
Protein Structure, Tertiary
EGTA
Endocrinology
chemistry
Energy Metabolism
Mitochondrial Swelling
Adenosine triphosphate
medicine.drug
Subjects
Details
- ISSN :
- 00165085
- Volume :
- 131
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Gastroenterology
- Accession number :
- edsair.doi.dedup.....792e01ee956f8c93b3c20cf45839bf20