Oxidative modifications of mitochondrial complex II are associated with insulin resistance of visceral fat in obesity

Am J Physiol Endocrinol Metab. 2019 Feb 1;316(2):E168-E177. doi: 10.1152/ajpendo.00227.2018. Epub 2018 Dec 21.


Obesity, particularly visceral adiposity, has been linked to mitochondrial dysfunction and increased oxidative stress, which have been suggested as mechanisms of insulin resistance. The mechanism(s) behind this remains incompletely understood. In this study, we hypothesized that mitochondrial complex II dysfunction plays a role in impaired insulin sensitivity in visceral adipose tissue of subjects with obesity. We obtained subcutaneous and visceral adipose tissue biopsies from 43 subjects with obesity (body mass index ≥ 30 kg/m2) during planned bariatric surgery. Compared with subcutaneous adipose tissue, visceral adipose tissue exhibited decreased complex II activity, which was restored with the reducing agent dithiothreitol (5 mM) ( P < 0.01). A biotin switch assay identified that cysteine oxidative posttranslational modifications (OPTM) in complex II subunit A (succinate dehydrogenase A) were increased in visceral vs. subcutaneous fat ( P < 0.05). Insulin treatment (100 nM) stimulated complex II activity in subcutaneous fat ( P < 0.05). In contrast, insulin treatment of visceral fat led to a decrease in complex II activity ( P < 0.01), which was restored with addition of the mitochondria-specific oxidant scavenger mito-TEMPO (10 µM). In a cohort of 10 subjects with severe obesity, surgical weight loss decreased OPTM and restored complex II activity, exclusively in the visceral depot. Mitochondrial complex II may be an unrecognized and novel mediator of insulin resistance associated with visceral adiposity. The activity of complex II is improved by weight loss, which may contribute to metabolic improvements associated with bariatric surgery.

Keywords: adipose tissue; insulin resistance; mitochondrial complex II; mitochondrial function; obesity; succinate dehydrogenase.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bariatric Surgery
  • Cysteine
  • Electron Transport Complex II / metabolism*
  • Female
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Insulin / pharmacology
  • Insulin Resistance*
  • Intra-Abdominal Fat / drug effects
  • Intra-Abdominal Fat / metabolism*
  • Male
  • Middle Aged
  • Obesity / metabolism*
  • Obesity / surgery
  • Organophosphorus Compounds / pharmacology
  • Oxidation-Reduction
  • Piperidines / pharmacology
  • Protein Processing, Post-Translational*
  • Subcutaneous Fat / drug effects
  • Subcutaneous Fat / metabolism


  • Hypoglycemic Agents
  • Insulin
  • MitoTEMPO
  • Organophosphorus Compounds
  • Piperidines
  • Electron Transport Complex II
  • Cysteine