title: Heart energy metabolism impairment in Western-diet induced obese mice.
abstract: Nutritional transition has contributed to growing obesity, mainly by changing eating habits of the population. The mechanisms by which diet-induced obesity leads to cardiac injury are not completely understood, but it is known that obesity is associated to impaired cardiac function and energy metabolism, increasing morbidity and mortality. Therefore, our study aimed to investigate the mechanisms underlying cardiac metabolism impairment related to Western diet-induced obesity. After weaning, male Swiss mice were fed a Western diet for 16 weeks in order to induce obesity. After this period, the content of proteins involved in heart energy metabolism GLUT1, cytosolic lysate and plasma membrane GLUT4, AMPK, pAMPK, IRβ, IRS-1, PGC-1α, CPT1 and UCP2 was evaluated. Also, the oxidative phosphorylation of myocardial fibers was measured by high-resolution respirometry. Mice in the Western diet group (WG) presented altered biometric parameters compared to those in control group, including higher body weight, increased myocardial lipid deposition and glucose intolerance, which demonstrate the obesogenic role of Western diet. WG presented increased CPT1 and UCP2 contents and decreased IRS-1, plasma membrane GLUT4 and PGC-1α contents. In addition, WG presented cardiac mitochondrial dysfunction and reduced biogenesis, demonstrating a lower capacity of carbohydrates and fatty acid oxidation and also decreased coupling between oxidative phosphorylation and adenosine triphosphate synthesis. Cardiac metabolism impairment related to Western diet-induced obesity is probably due to damaged myocardial oxidative capacity, reduced mitochondrial biogenesis and mitochondria uncoupling, which compromise the bioenergetic metabolism of heart.
authors: Laboratory of Nutrition Physiology and Development, Department of Physiological Sciences, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Fabiana A
authors: FA
authors: Neves
authors: Erika
authors: E
authors: Cortez
authors: Amélia F
authors: AF
authors: Bernardo
authors: Ana B M
authors: AB
authors: Mattos
authors: Anatalia K
authors: AK
authors: Vieira
authors: Tayanne de O
authors: Tde O
authors: Malafaia
authors: Alessandra A
authors: AA
authors: Thole
authors: Alessandra C de S
authors: AC
authors: Rodrigues-Cunha
authors: Erica P
authors: EP
authors: Garcia-Souza
authors: Rosely
authors: R
authors: Sichieri
authors: Anibal S
authors: AS
authors: Moura
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism; D004032:Diet / Q000009:adverse effects*; D004734:Energy Metabolism; D005951:Glucose Tolerance Test; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D006321:Heart / Q000503:physiopathology*; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008820:Mice, Obese; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D063269:Mitochondrial Turnover; D009206:Myocardium; D010085:Oxidative Phosphorylation; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071246:Uncoupling Protein 2; D015430:Weight Gain
chemical_list: D051272:Glucose Transporter Type 1; D051275:Glucose Transporter Type 4; D055504:Insulin Receptor Substrate Proteins; D007473:Ion Channels; C526295:Irs1 protein, mouse; D024101:Mitochondrial Proteins; C495678:Slc2a1 protein, mouse; C495693:Slc2a4 protein, mouse; D014157:Transcription Factors; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; D000255:Adenosine Triphosphate; D002334:Carnitine O-Palmitoyltransferase
keywords: Diet-induced obesity; Mitochondrial bioenergetics; Mitochondrial biogenesis; Mitochondrial impairment; Western diet