Wednesday, 2 April 2014

Defective adipocytes in obesity

:Back to this paper....

First, you have to harvest some (pre)adipocytes from obese and lean people. You then grow them like this....

Growth for 24–48 h in preadipocyte media (PM-1; Zen-Bio) contained Dulbecco's modified Eagle's medium F12 (DMEM/F12 [1:1, v/v]), HEPES (pH 7.4), 10% FBS, and antibiotics.
Cells were differentiated for 7 days in media containing DMEM/F12 (1:1; v/v), HEPES (pH 7.4), 10% FBS, biotin, pantothenate, insulin, dexamethasone, isobutylmethylxanthine (IBMX), and a nonthiazolidinedione peroxisome proliferator–activated receptor (PPAR)-╬│ agonist (DM-2; Zen-Bio),
followed by an additional week in adipocyte maintenance media (DM-2 without IBMX and PPAR╬│ agonist

You then add the mitochondrial uncoupler FCCP to the mix and measure the increase in the oxygen consumption rate ( as compared to basal ) of those cells from obese people vs lean people, and you wind up with this graph....

Which tells you that under equal conditions, adipocytes from lean people have greater ability to oxidize fuels ( fats?) compared to adipocytes from obese people. The authors of the paper have no explanation for this particular finding with FCCP. I think it suggests an intrinsic defect in the adipocytes of obese people.

Isoproterenol induced increase in oxygen consumption was also impaired in adipocytes from obese people.

So whats responsible for the reduction in oxygen consumption in Isoproterenol? And is it the same defect responsible for the FCCP deficit? Again this remains unknown.

However, they did determine that the reduction in Isoproterenol induced oxygen consumption was NOT due to....

  • impaired differentiation of the adipocytes
  • differences in mitochondrial mass
  • differences in gene expression of mitochondrial proteins 
  • a reduction in Isoproterenol-stimulated lipolysis 
  • PKA activity
  • initial differences in basal oxygen consumption
  • Beta-receptor subtype expression

So we are left scratching our heads. We know that obese people store too many adipocytes. And here we have found that adipocytes from obese people have an intrinsic defect in oxygen consumption when exposed to stimuli that increase energy expenditure. Alas, the penny hasnt dropped yet.

Although this isnt proof of a cause of obesity, a burning question is, how easy is it to stay lean when your body is infested with these "lazy" fat cells?

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