Induction of Cardiac Uncoupling Protein-2 Expression and Adenosine 5′-Monophosphate-Activated Protein Kinase Phosphorylation during Early States of Diet-Induced Obesity in Mice

• DOI: 10.1210/en.2006-0914
• Publication Date: 2006-11-03T03:17:59Z
• Authors: Beatriz Somoza; Rocío Guzmán; Victoria Cano; Beatriz Merino; Pilar Ramos; Carmen Díez-Ferná...; Maria S. Fernánde...; Mariano Ruiz-Gayo
• Keywords: Male; STAT3 Transcription Factor; 2. Zero hunger; 0303 health sciences; L-Lactate Dehydrogenase; Myocardium; Body Weight; Phosphotransferases; Mice, Obese; AMP-Activated Protein Kinases; Protein Serine-Threonine Kinases; Ion Channels; Diet; Mice, Inbred C57BL; Mitochondrial Proteins; Mice; 03 medical and health sciences; Multienzyme Complexes; Animals; Body Fat Distribution; Diet, Atherogenic; Obesity; Phosphorylation

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.