Strong association between mitochondrial DNA copy number and lipogenesis in human white adipose tissue.
OBJECTIVE
Recent studies suggest a link between insulin resistance and mitochondrial function in white fat cells. The aim of this study was to evaluate adipocyte mitochondrial DNA (mtDNA) copy number in relation to adipocyte and clinical variables that are related to insulin sensitivity.


METHODS
We studied a group of 148 healthy volunteers with a large inter-individual variation in BMI. Relative amounts of mtDNA and nuclear DNA were determined by quantitative RT-PCR. The mtDNA:nuclear DNA ratio reflects the tissue concentration of mtDNA per cell.


RESULTS
The mtDNA copy number was enriched in adipocytes of adipose tissue and decreased slightly by ageing (p = 0.015) and increasing BMI (p = 0.004); however, it was not influenced by sex, energy-restricted diets or marked long-term weight reduction. Adipose mtDNA copy number was not independently related to resting energy expenditure, overall insulin sensitivity or adipocyte lipolysis. However, it showed a strong positive correlation with basal (p = 0.0012) and insulin-stimulated lipogenesis (p < 0.0001) in fat cells, independently of age and BMI, and a weak positive correlation with levels of mRNA from several genes involved in mitochondrial oxidative capacity (r = 0.2-0.3).


CONCLUSIONS
The mtDNA copy number in human white fat cells is fairly stable within healthy individuals. It is not influenced by sex or weight loss and is not important for overall insulin sensitivity or energy expenditure at rest. However, it is strongly related to adipocyte lipogenesis and weakly to mitochondrial oxidative capacity, suggesting that adipocyte mitochondria are, above all, local regulators.
Kaaman
M
M
Karolinska Institute at Department of Medicine, Huddinge, Karolinska University Hospital, M61, Stockholm, Sweden.
Sparks
L M
LM
van Harmelen
V
V
Smith
S R
SR
Sjölin
E
E
Dahlman
I
I
Arner
P
P
D052438:Adipocytes, White / Q000378:metabolism / Q000502:physiology; D052436:Adipose Tissue, White / Q000378:metabolism* / Q000502:physiology; D000328:Adult; D000367:Age Factors; D050110:Bariatric Surgery; D015992:Body Mass Index; D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000502:physiology*; D004036:Diet, Atherogenic; D018752:Diet, Fat-Restricted; D005260:Female; D005500:Follow-Up Studies; D018628:Gene Dosage; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D050155:Lipogenesis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D016032:Randomized Controlled Trials as Topic; D012727:Sex Characteristics; D015431:Weight Loss / Q000502:physiology
D004272:DNA, Mitochondrial