title: Hyperlipidemic mice present enhanced catabolism and higher mitochondrial ATP-sensitive K+ channel activity.
abstract: OBJECTIVE
  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.
authors.affiliation: Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, 13083-970 Campinas, São Paulo, Brazil.
authors.forename: Luciane C
authors.initials: LC
authors.lastname: Alberici
authors.forename: Helena C F
authors.initials: HC
authors.lastname: Oliveira
authors.forename: Patrícia R
authors.initials: PR
authors.lastname: Patrício
authors.forename: Alicia J
authors.initials: AJ
authors.lastname: Kowaltowski
authors.forename: Anibal E
authors.initials: AE
authors.lastname: Vercesi
mesh_terms: D000818:Animals; D053305:Apolipoprotein C-III / Q000235:genetics; D001831:Body Temperature / Q000502:physiology; D019069:Cell Respiration / Q000502:physiology; D004435:Eating / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology*; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D006949:Hyperlipidemias / Q000378:metabolism*; D008660:Metabolism / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D008930:Mitochondria, Liver / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000502:physiology; D015221:Potassium Channels / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary
chemical_list: D053305:Apolipoprotein C-III; D005227:Fatty Acids; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel