Mitochondrial energy metabolism and redox responses to hypertriglyceridemia

Abstract

In this work we review recent findings that explain how mitochondrial bioenergetic functions and redox state respond to a hyperlipidemic in vivo environment and may contribute to the maintenance of a normal metabolic phenotype. The experimental model utilized to evidence these adaptive mechanisms is especially useful for these studies since it exhibits genetic hypertriglyceridemia and avoids complications introduced by high fat diets. Liver from hypertrigliceridemic (HTG) mice have a greater content of glycerolipids together with increased mitochondrial free fatty acid oxidation. HTG liver mitochondria have a higher resting respiration rate but normal oxidative phosphorylation efficiency. This is achieved by higher activity of the mitochondrial potassium channel sensitive to ATP (mitoKATP). The mild uncoupling mediated by mitoKATP accelerates respiration rates and reduces reactive oxygen species generation. Although this response is not sufficient to inhibit lipid induced extra-mitochondrial oxidative stress in whole liver cells it avoids amplification of this redox imbalance. Furthermore, higher mitoKATP activity increases liver, brain and whole body metabolic rates. These mitochondrial adaptations may explain why these HTG mice do not develop insulin resistance and obesity even under a severe hyperlipidemic state. On the contrary, when long term high fat diets are employed, insulin resistance, fatty liver and obesity develop and mitochondrial adaptations are inefficient to counteract energy and redox imbalances.

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Correspondence to Luciane C. Alberici.

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Alberici, L.C., Vercesi, A.E. & Oliveira, H.C.F. Mitochondrial energy metabolism and redox responses to hypertriglyceridemia. J Bioenerg Biomembr 43, 19–23 (2011). https://doi.org/10.1007/s10863-011-9326-y

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Keywords

  • Hypertriglyceridemia
  • Mitochondrial uncoupling
  • Redox state
  • Mitochondrial ATP-sensitive potassium channels