An overview of the crosstalk between inflammatory processes and metabolic dysregulation during diabetic cardiomyopathy.
Metabolic disorders such as obesity, insulin resistance and type 2 diabetes mellitus are all linked to cardiovascular diseases such as cardiac hypertrophy and heart failure. Diabetic cardiomyopathy in particular, is characterized by structural and functional alterations in the heart muscle of people with diabetes that finally lead to heart failure, and which is not directly attributable to coronary artery disease or hypertension. Several mechanisms have been involved in the pathogenesis of diabetic cardiomyopathy, such as alterations in myocardial energy metabolism and calcium signaling. Metabolic disturbances during diabetic cardiomyopathy are characterized by increased lipid oxidation, intramyocardial triglyceride accumulation, and reduced glucose utilization. Overall changes result in enhanced oxidative stress, mitochondrial dysfunction and apoptosis of the cardiomyocytes. On the other hand, the progression of heart failure and cardiac hypertrophy usually entails a local rise in cytokines in cardiac cells and the activation of the proinflammatory transcription factor nuclear factor (NF)-κB. Interestingly, increasing evidences are arising in the recent years that point to a potential link between chronic low-grade inflammation in the heart and metabolic dysregulation. Therefore, in this review we summarize recent new insights into the crosstalk between inflammatory processes and metabolic dysregulation in the failing heart during diabetes, paying special attention to the role of NF-κB and peroxisome proliferator activated receptors (PPARs). In addition, we briefly describe the role of the AMP-activated protein kinase (AMPK), sirtuin 1 (SIRT1) and other pathways regulating cardiac energy metabolism, as well as their relationship with diabetic cardiomyopathy.
Department of Pharmacology and Therapeutic Chemistry, IBUB (Institut de Biomedicina de la Universitat de Barcelona), Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Faculty of Pharmacy, University of Barcelona, Diagonal 643, Barcelona E-08028, Spain.
Xavier
X
Palomer
Laia
L
Salvadó
Emma
E
Barroso
Manuel
M
Vázquez-Carrera
D000818:Animals; D058065:Diabetic Cardiomyopathies / Q000378:metabolism* / Q000473:pathology*; D004734:Energy Metabolism / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000378:metabolism; D050356:Lipid Metabolism / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
D007328:Insulin; D005947:Glucose
ACO; ACS; AMP-activated protein kinase; AMPK; CPT; Cardiovascular Disease; ERK1/2; ERR; FABP; FAT/CD36; FATP; FOXO1; Heart; IKK; IL-6; Inflammation; IκB kinase; JNK; LDL; LPL; MAPK; MCAD; MCP-1; Metabolism; NADH; NF-κB; NFAT; PDC; PDK; PGC-1α; PI3K; PKB/Akt; PPAR; PPRE; ROS; RXR; SAFE; SIRT1; SOCS; STAT; TCA; TNF-α; acyl-CoA oxidase; acyl-CoA synthase; c-Jun N-terminal kinase; calcineurin-nuclear factor of activated T cells; carnitine palmitoyl transferase; estrogen-related receptor; extracellular signal-regulated protein kinase 1/2; fatty acid binding protein; fatty acid translocase/CD36; fatty acid transport protein; forkhead transcription factor; interleukin 6; lipoprotein lipase; low density lipoprotein; medium-chain acyl-CoA dehydrogenase; mitogen-activated protein kinase; monocyte chemoattractant protein-1; nicotinamide adenine dinucleotide; nuclear factor-κB; peroxisome proliferator response element; peroxisome proliferator-activated receptor; peroxisome proliferator-activated receptor γ coactivator-1α; phosphatidylinositol 3 kinase; protein kinase B; pyruvate dehydrogenase complex; pyruvate dehydrogenase kinase; reactive oxygen species; retinoid X receptor; signal transducer and activator of transcription; sirtuin 1; suppressor of cytokine signaling; survival activating factor enhancement; tricarboxylic acid cycle; tumor necrosis factor-α