Adipose tissue mitochondrial dysfunction triggers a lipodystrophic syndrome with insulin resistance, hepatosteatosis, and cardiovascular complications

FASEB J. 2014 Oct;28(10):4408-19. doi: 10.1096/fj.14-253971. Epub 2014 Jul 8.


Mitochondrial dysfunction in adipose tissue occurs in obesity, type 2 diabetes, and some forms of lipodystrophy, but whether this dysfunction contributes to or is the result of these disorders is unknown. To investigate the physiological consequences of severe mitochondrial impairment in adipose tissue, we generated mice deficient in mitochondrial transcription factor A (TFAM) in adipocytes by using mice carrying adiponectin-Cre and TFAM floxed alleles. These adiponectin TFAM-knockout (adipo-TFAM-KO) mice had a 75-81% reduction in TFAM in the subcutaneous and intra-abdominal white adipose tissue (WAT) and interscapular brown adipose tissue (BAT), causing decreased expression and enzymatic activity of proteins in complexes I, III, and IV of the electron transport chain (ETC). This mitochondrial dysfunction led to adipocyte death and inflammation in WAT and a whitening of BAT. As a result, adipo-TFAM-KO mice were resistant to weight gain, but exhibited insulin resistance on both normal chow and high-fat diets. These lipodystrophic mice also developed hypertension, cardiac hypertrophy, and cardiac dysfunction. Thus, isolated mitochondrial dysfunction in adipose tissue can lead a syndrome of lipodystrophy with metabolic syndrome and cardiovascular complications.

Keywords: BAT; TFAM; WAT; cardiomegaly; diabetes; hypertension.

Publication types

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

MeSH terms

  • Adiponectin / genetics
  • Adiponectin / metabolism
  • Adipose Tissue, Brown / metabolism*
  • Adipose Tissue, Brown / pathology
  • Adipose Tissue, White / metabolism*
  • Adipose Tissue, White / pathology
  • Animals
  • Cardiomegaly / genetics
  • Cardiomegaly / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Electron Transport Chain Complex Proteins / metabolism
  • Fatty Liver / genetics
  • Fatty Liver / metabolism
  • Fatty Liver / pathology
  • High Mobility Group Proteins / genetics
  • High Mobility Group Proteins / metabolism*
  • Hypertension / genetics
  • Hypertension / metabolism
  • Insulin Resistance*
  • Lipodystrophy / genetics
  • Lipodystrophy / metabolism*
  • Lipodystrophy / physiopathology
  • Male
  • Mice
  • Mitochondria / metabolism*
  • Weight Gain


  • Adiponectin
  • DNA-Binding Proteins
  • Electron Transport Chain Complex Proteins
  • High Mobility Group Proteins
  • Tfam protein, mouse