Cardiac substrate uptake and metabolism in obesity and type-2 diabetes: role of sarcolemmal substrate transporters.

Cardiovascular disease is the primary cause of death in obesity and type-2 diabetes mellitus (T2DM). Alterations in substrate metabolism are believed to be involved in the development of both cardiac dysfunction and insulin resistance in these conditions. Under physiological circumstances the heart utilizes predominantly long-chain fatty acids (LCFAs) (60-70%), with the remainder covered by carbohydrates, i.e., glucose (20%) and lactate (10%). The cellular uptake of both LCFA and glucose is regulated by the sarcolemmal amount of specific transport proteins, i.e., fatty acid translocase (FAT)/CD36 and GLUT4, respectively. These transport proteins are not only present at the sarcolemma, but also in intracellular storage compartments. Both an increased workload and the hormone insulin induce translocation of FAT/CD36 and GLUT4 to the sarcolemma. In this review, recent findings on the insulin and contraction signalling pathways involved in substrate uptake and utilization by cardiac myocytes under physiological conditions are discussed. New insights in alterations in substrate uptake and utilization during insulin resistance and its progression towards T2DM suggest a pivotal role for substrate transporters. During the development of obesity towards T2DM alterations in cardiac lipid homeostasis were found to precede alterations in glucose homeostasis. In the early stages of T2DM, relocation of FAT/CD36 to the sarcolemma is associated with the myocardial accumulation of triacylglycerols (TAGs) eventually leading to an impaired insulin-stimulated GLUT4-translocation. These novel insights may result in new strategies for the prevention of development of cardiac dysfunction and insulin resistance in obesity and T2DM.

Erratum to: Molecular and Cellular Biochemistry 277, 284, 286, 299

The proceedings of the 5th International Conference on Lipid Binding Proteins, held in Sendai, September 2004, were scheduled to be published as a single Focussed Issue of Molecular and Cellular Biochemistry. Due to an unfortunate error at the publisher’s the various contributions to these proceedings have been published in four distinct issues of Molecular and Cellular Biochemistry, i.e., volumes 277, 284, 286, and 299. Below please find the Preface for this collection of papers, and a listing of the constituting articles together with a reference to the exact source. Note that six articles appear in the present issue of Molecular and Cellular Biochemistry.

Preface

For a long time it was believed that lipids are solely building blocks of cellular membranes and sources of metabolic energy. However, it is now well established that various lipids, including fatty acids, vitamins, cholesterol and ceramides, function in concert with lipid-binding proteins (LBPs) to play important roles in cellular lipid metabolism and signal transduction, whose alterations consequently affect the condition of our health and disease in various manners. LBPs include the intra- and extracellular lipid carrier proteins, lipid-modifying enzymes and its receptors. Indeed, some metabolic diseases, such as atherosclerosis and (type-2) diabetes, have been characterized by malfunctioning of LBPs or by mutation in genes encoding LBPs. Therefore, we are now directing our further attention toward the role of LBPs to clarify the mechanism underlying lipid-mediated physiological and pathological phenomena in health and diseases.

In view of this growing interest in LBPs, a series of International Conferences on Lipid Binding Proteins have been held in Maastricht (1989, 1992, 2001) and Minneapolis (1997). Following the success of these conferences, the 5th Conference was held in September 2004 in Sendai, as the first one outside Europe and America. Participants came from more than ten countries, presented their recent research results, and discussed actively the scientific basis and implications of LBPs from their different specialties. Selected articles in some previous and the present issue of Molecular and Cellular Biochemistry form a collection of papers from the lectures and poster presentations during the conference, and will provide the updated understanding of the significance of LBPs in health and diseases.

Hisatake Kondo, MD, PhD

Yuji Owada, MD, PhD

Jan F.C. Glatz, PhD

Guest Editors

TABLE OF CONTENTS

1.	10.1007/s11010-005-9029-y	H. Kondo, Y. Owada and J.F.C. Glatz “Preface”
2.		T. Ono: Studies of the FABP family: A retrospective. MCB 277: 1–6, 2005
3.	10.1007/s11010-005-9030-5	S.L.M. Coort, A. Bonen, G.J. Van der Vusse, J.F.C. Glatz, J.J.F.P. Luken: Cardiac substrate uptake and metabolism in obesity and type-2 diabetes: Role of sarcolemmal substrate transporters.
4.	10.1007/s11010-005-9031-4	S. Yamashita, K. Hirano, T. Kuwasako, M. Janabi, Y. Toyama, M. Ishigami, N. Sakai: Physiological and pathological roles of a multi-ligand receptor CD36 in atherogenesis. Insights from CD36-deficient patients.
5.	10.1007/s11010-005-9032-3	T. Tanaka, K. Sohmiya, T. Kono, F. Terasaki, R. Horie, Y. Ohkaru, M. Muramatsu, S. Takai, M. Miyazaki, Y. Kitaua: Thiamine attenuates the hypertension and metabolic abnormalities in CD36-defective SHR. Uncoupling of glucose oxidation from cellular entry accompanied with enhanced protein O-GlcNAcylation in CD36-deficiency.
6.	10.1007/s11010-005-9033-2	J.F.F. Brinkmann, M.M.A.L. Pelsers, F.A. Van Nieuwenhoven, N.N. Tandon, G.J. Van der Vusse, J.F.C. Glatz: Purification, immunochemical quantification and localization in rat heart of putative fatty acid translocase (FAT/CD36). MCB 284, 127–134, 2006
7.	10.1007/s11010-005-9034-1	R. Ehehalt, J. Füllekrug, J. Pohl, A. Ring, T. Hermann, W. Stremmel: Translocation of long-chain fatty acids across the plasma membrane – lipid rafts and fatty acid transport proteins. MCB 284, 135–140, 2006
8.	10.1007/s11010-005-9035-0	O. Sato, N. Takanashi, K. Motojima: Third promoter and differential regulation of mouse and human fatty acid translocase/CD36 genes.
9.	10.1007/s11010-005-9036-2	H. Qu, L. Cui, J. Rickers-Haunerland, N.H. Haunerland: Fatty acid-dependent expression of the muscle FABP gene. Comparative analysis of gene control in functionally related, but evolutionary distant animal systems.
10.	10.1007/s11010-005-9052-z	M. Shimizu, D. Yamashita, T. Yamaguchi, F. Hirose, T. Osumi: Aspects of the regulatory mechanisms of PPAR functions: analysis of a bidirectional response element and regulation by sumoylation. MCB 286, 33–42, 2006
11.	10.1007/s11010-005-9038-x	O. Ito, Y. Nakamura, L. Tan, T. Ishizuka, Y. Sasaki, N. Minami, M. Kanazawa, S. Ito, H. Sasano, M. Kohzuki: Expression of cytochrome P-450 4 enzymes in the kidney and liver. Regulation by PPAR and species-difference between rat and human. MCB 284, 141–148, 2006
12.	10.1007/s11010-005-9039-9	D. Neess, P. Kiilerich, M.B. Sandberg, T. Helledie, R. Nielsen, S. Mandrup: ACBP - a PPAR and SREBP modulated housekeeping gene. MCB 284, 149–157, 2006
13.	10.1007/s11010-005-9040-3	N.J. Færgeman, M. Wadum, S. Feddersen, M. Burton, B.B. Kragelund, J. Knudsen: Acyl-CoA binding proteins; structural and functional conservation over 2000 mya.
14.	10.1007/s11010-005-9041-2	A.E. Thumser, J. Storch: Characterization of a BODIPY-labeled fluorescent fatty acid analogue. Binding to fatty acid-binding proteins, intracellular localization, and metabolism.
15.	10.1007/s11010-005-9042-1	L.B. Agellon, L. Li, L. Luong, R.R.E. Uwiera: Adaptations to the loss of intestinal fatty acid-binding protein in mice. MCB 284, 159–166, 2006
16.	10.1007/s11010-005-9043-0	B. Binas, E. Erol: FABPs as determinants of myocellular and hepatic fuel metabolism.
17.	10.1007/s11010-005-9044-z	K. Hanada: Discovery of the molecular machinery CERT for endoplasmic reticulum-to-Golgi trafficking of ceramide. MCB 286, 23–31, 2006
18.	10.1007/s11010-005-9045-y	T. Yamaguchi, N. Omatsu, A. Omukae, T. Osumi: Analysis of interact partners for perilipin and ADRP on lipid droplets. MCB 284, 167–173, 2006
19.	10.1007/s11010-005-9046-x	D. Yao, M. Kuwajima, Y. Chen, M. Shiota, Y. Okumura, H. Yamada, H. Kido: Impaired long-chain fatty acid metabolism in mitochondria causes brain vascular invasion by a non-neurotropic epidemic influenza A virus in the newborn/suckling period: implications for influenza-associated encephalopathy.
20.	10.1007/s11010-005-9047-9	A. Kamijo, T. Sugaya, A. Hikawa, M. Yamanouchi, Y. Hirata, T. Ishimitsu, A. Numabe, M. Takagi, H. Hayakawa, F. Tabei, T. Sugimoto, N. Mise, M. Omata, K. Kimura: Urinary liver-type fatty acid binding protein as a useful biomarker in chronic kidney disease. MCB 284, 175–182, 2006
21.	10.1007/s11010-005-9048-8	Y. Kusakari, E. Ogawa, Y. Owada, N. Kitanaka, H. Watanabe, M. Kimura, H. Tagami, H. Kondo, S. Aiba, R. Okuyama: Decreased keratinocyte motility in skin wound on mice lacking the epidermal fatty acid binding protein gene. MCB 284, 183–188, 2006
22.	10.1007/s11010-005-9049-7	H. Luo, A. Kashiwagi, T. Shibahara, K. Yamada: Decreased body weight without rebound and regulated lipoprotein metabolism by gymnemate in genetic multifactor syndrome animal.
23.	10.1007/s11010-005-9050-1	S.A. Abdelwahab, Y. Owada, N. Kitanaka, A. Adida, H. Sakagami, M. Ono, M. Watanabe, F. Spener, H. Kondo: Enhanced expression of adipocyte-type fatty acid binding protein in murine lymphocytes in response to dexamethasone treatment.