The effect of weight reduction on skeletal muscle UCP2 and UCP3 mRNA expression and UCP3 protein content in Type II diabetic subjects.
OBJECTIVE
The aim of this study was to examine the effect of weight loss on UCP2/UCP3 mRNA expression and UCP3 protein content in subjects with Type II (non-insulin-dependent) diabetes mellitus.


METHODS
We studied seven Type II diabetic subjects who followed a 10-week very low calorie diet. Expression of skeletal muscle UCP2 and UCP3 mRNA was measured using RT-competitive PCR and UCP3 protein content by western blotting, before and after the diet. Total and plasma fatty acid oxidation was measured using infusion of 13C labelled palmitate.


RESULTS
Body weight decreased from 105.5 +/- 8.2 kg to 91.6 +/- 7.2 kg (p < 0.001), after 10 weeks of diet intervention. Expression of UCP2 and UCP3 mRNA were significantly reduced after 10 weeks of diet (p < 0.05) but UCP3 protein contents were not significantly altered. Notably, the change in UCP3L mRNA expression and UCP3 protein content after the very low calorie diet were negatively associated with changes in body weight (r = -0.97, p = 0.006 and r = -0.83, p = 0.043, respectively) and BMI (r = -0.99, p = 0.0007 and r = -0.9, p = 0.016, respectively). Furthermore, changes in UCP3L mRNA expression and UCP3 protein content induced by the diet were positively correlated with changes in cytosolic fatty acid-binding protein content (r = 0.93, p = 0.023 and r = 0.84, p = 0.039, respectively). No correlation between diet-induced changes in UCP3 protein and resting energy expenditure or plasma non-esterified fatty acid concentrations were found.


CONCLUSIONS
The negative correlation between the change in UCP3 protein content after weight loss and the change in BMI, suggests that the decrease in UCP3 during weight loss could prevent further weight loss. The finding that the change in UCP3 protein content correlates with the change in skeletal muscle fatty acid-binding protein content, suggests a role for UCPs in the handling of lipids as a fuel.
Schrauwen
P
P
Department of Human Biology, Maastricht University, The Netherlands.
Schaart
G
G
Saris
W H
WH
Slieker
L J
LJ
Glatz
J F
JF
Vidal
H
H
Blaak
E E
EE
D000918:Antibody Specificity; D001706:Biopsy; D015992:Body Mass Index; D002352:Carrier Proteins / Q000032:analysis* / Q000235:genetics*; D003920:Diabetes Mellitus / Q000178:diet therapy / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000178:diet therapy / Q000378:metabolism*; D004038:Diet, Reducing; D002149:Energy Intake; D004734:Energy Metabolism; D015870:Gene Expression; D006801:Humans; D015151:Immunoblotting; D007473:Ion Channels; D008297:Male; D026901:Membrane Transport Proteins; D008875:Middle Aged; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism*; D009765:Obesity; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D014475:Uncoupling Agents / Q000032:analysis; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D015431:Weight Loss
D002352:Carrier Proteins; D007473:Ion Channels; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D012333:RNA, Messenger; C000604389:UCP2 protein, human; C000604392:UCP3 protein, human; D014475:Uncoupling Agents; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3