Biphasic response of mitochondrial biogenesis to oxidative stress in visceral fat of diet-induced obesity mice

Pei Wen Wang, Hsiao Mei Kuo, Hung Tu Huang, Alice Yw Chang, Shao Wen Weng, Ming Hong Tai, Jiin Haur Chuang, I. Ya Chen, Shun Chen Huang, Tsu Kung Lin, Chia Wei Liou

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


Aims: Studies in skeletal muscle demonstrate a strong association of mitochondrial dysfunction with insulin resistance (IR). However, there is still a paucity of knowledge regarding the alteration of mitochondria in adipose tissue (AT) in the pathogenesis of IR in obesity. We investigated the mitochondrial biogenesis in visceral fat (VF) and subcutaneous fat (SF) in C57BL/6J mice fed a high-fat high-sucrose diet for 12 months. Results: Impairment of glucose tolerance and insulin sensitivity developed after 1 month of the diet and was associated with a prompt increase of VF. The VF adipocytes were larger than those in the SF and had increased expressions of HIF-1α and p-NFκB p65. However, the alteration of mitochondrial biogenesis did not occur in the early stage when increased intracellular reactive oxygen species (ROS), mitochondrial oxygen consumption rate, and mitochondrial ROS emerged at the 1st, 2nd and 2nd month, respectively. Until the 6th month, the VF had markedly increased mitochondrial DNA content and expression of PGC-1α, Tfam, ATP5A, and MnSOD. This increase of mitochondrial biogenesis was followed by a generalized decrease at the 12th month and the mitochondrial morphology altered markedly. In the late stage, although mitochondrial ROS decreased, the increased expression of 8-OHdG in VF continued. Innovation and Conclusion: These data suggest that IR and ROS production occur before the biphasic changes of mitochondrial biogenesis in AT, and the VF plays a more crucial role.

Original languageEnglish
Pages (from-to)2572-2588
Number of pages17
JournalAntioxidants and Redox Signaling
Issue number16
Publication statusPublished - 2014 Jun 1

All Science Journal Classification (ASJC) codes

  • Physiology
  • Biochemistry
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology


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