Induction of cardiac uncoupling protein-2 expression and adenosine 5'-monophosphate-activated protein kinase phosphorylation during early states of diet-induced obesity in mice.
The objective of this work was to characterize the adaptation of cardiac metabolism to a lipid overload in a model of diet-induced obesity (DIO) in mice. After 8 wk dietary treatment, mice receiving a high-fat diet exhibited an increase in the amount of adipose tissue, accompanied by a surge in plasma leptin concentration (from 5.4-16.0 ng/ml). This was associated with: 1) an induction of uncoupling protein-2 (120%), 2) an increase in the phosphorylated form of AMP-activated protein kinase (120%), and 3) a reduction in lactate concentration and lactate dehydrogenase activity in myocardial tissue (40%). Because DIO induces leptin resistance, we analyzed leptin receptor functionality by measuring phospho-signal transducer and activator of transcription 3 in response to acute leptin (1 mg/kg). We observed that leptin receptor signaling remained unaltered within the heart but was fully impaired within the hypothalamus. Taken together, these data show that during DIO development, there is a metabolic shift in the heart aimed at increasing fatty acid oxidation to the detriment of carbohydrates. This effect seems to be leptin-dependent, suggesting that the increased adiposity observed during the onset of obesity might contribute to impairing ectopic lipidic deposition in the heart.
Somoza
Beatriz
B
Departamento de Farmacología, Tecnología y Desarrollo Farmacéutico, Facultad de Farmacia, Universidad San Pablo-Ceu, Urbanización Montepríncipe, Carretera de Boadilla del Monte km 5,3 Boadilla del Monte, 28668 Madrid, Spain.
Guzmán
Rocío
R
Cano
Victoria
V
Merino
Beatriz
B
Ramos
Pilar
P
Díez-Fernández
Carmen
C
Fernández-Alfonso
Maria S
MS
Ruiz-Gayo
Mariano
M
D055372:AMP-Activated Protein Kinases; D000818:Animals; D050218:Body Fat Distribution; D001835:Body Weight; D004032:Diet / Q000009:adverse effects; D004036:Diet, Atherogenic; D007473:Ion Channels / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism*; D009206:Myocardium / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D009765:Obesity / Q000209:etiology / Q000378:metabolism*; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014280:Triglycerides / Q000032:analysis; D000071246:Uncoupling Protein 2
D007473:Ion Channels; D024101:Mitochondrial Proteins; D009097:Multienzyme Complexes; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D014280:Triglycerides; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D007770:L-Lactate Dehydrogenase; D010770:Phosphotransferases; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases