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Free keywords:
Adiponectin/genetics/metabolism
Adipose Tissue, Brown/*metabolism/pathology
Adipose Tissue, White/*metabolism/pathology
Animals
Cardiomegaly/genetics/metabolism
DNA-Binding Proteins/genetics/*metabolism
Electron Transport Chain Complex Proteins/metabolism
Fatty Liver/genetics/metabolism/pathology
High Mobility Group Proteins/genetics/*metabolism
Hypertension/genetics/metabolism
*Insulin Resistance
Lipodystrophy/genetics/*metabolism/physiopathology
Male
Mice
Mitochondria/*metabolism
Weight Gain
Bat
Tfam
Wat
cardiomegaly
diabetes
hypertension
Abstract:
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.
