Insulin-Like Effect of Low-Dose Leptin on Glucose Transport in Langendorff Rat Hearts

Haap, Michael; Houdali, B.; Maerker, Elke; Renn, W.; Machicao, Fausto; Hm, Hoffmeister; Häring, HU; Rett, K.

doi:10.1055/s-2003-39786

Cited by 12 publications

(5 citation statements)

References 36 publications

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“…In HL‐1 cardiomyocytes and an isolated working heart, leptin had no effect on glucose utilization. In contrast to these findings, a study of Langendorff‐perfused rat hearts showed that leptin stimulated glucose uptake 79 . Additionally, in Zucker rats, a reduction in glucose metabolism has been described even before the onset of hyperglycaemia 80 .…”

Section: Leptin and Cardiovascular Diseasementioning

confidence: 95%

Leptin and cardiovascular diseases

Hou

Luo

2011

Clin Exp Pharma Physio

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1. Leptin is a 16-kDa hormone, synthesized primarily by adipocyte, which acts as a key factor for maintenance of energy homeostasis in central and peripheral tissues. In most obese individuals, serum leptin levels are increased and correlate with the individual's body mass index. 2. Abundant investigations ranging from clinical and animal model studies to in vitro analyses show that leptin plays a pivotal role in obesity-related cardiovascular diseases (CVD). Hyperleptinaemia has been confirmed to be a predictor of acute cardiovascular events. However, some studies have shown that leptin has a cardioprotective effect in leptin-deficient models. These data suggest the influences of leptin on the pathophysiology of cardiovascular diseases are complex and not completely understood. 3. In the present review, we summarize the major leptin signalling pathways, including Janus-activated kinase/signal transducers and activators of transcription (Jak/STAT), mitogen-activated protein kinases (MAPK), and phosphatidylinositol 3-kinase (PI-3K) signalling pathways, and analyse the probable mechanisms of selective leptin resistance. We then provide a detailed review of the effects of leptin on the cardiovascular system, including sympathoactivation, oxidative stress, vascular inflammation, endothelial dysfunction, vascular cell proliferation, cardiomyocytes hypertrophy, as well as fatty acid metabolism, all of which contribute to the pathogenesis of cardiovascular diseases (e.g. ischaemic heart disease). The central premise of this review is to elucidate the mechanisms by which leptin affects the cardiovascular function and provide insight into obesity-related CVD.

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Section: Leptin and Cardiovascular Diseasementioning

confidence: 95%

Leptin and cardiovascular diseases

Hou

Luo

2011

Clin Exp Pharma Physio

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“…155 Yet, in a Langendorff perfused rat heart, a dose of 1 ng/mL leptin produces a significant increase in glucose uptake. 156 Of interest is that ischemia causes a downregulation of leptin and leptin receptor gene expression, which suggests there may be an interesting link between ischemic heart disease and leptin; however, further studies are required to better delineate this link. 157 Two experimental studies have examined the effects of ischemia/reperfusion on leptin and leptin receptor gene expression with conflicting results.…”

Section: Leptin Regulation Of Myocardial Metabolismmentioning

confidence: 99%

Cardiac Energy Metabolism in Obesity

Lopaschuk

Folmes²,

Stanley

2007

Circulation Research

251

208

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Abstract-Obesity results in marked alterations in cardiac energy metabolism, with a prominent effect being an increase in fatty acid uptake and oxidation by the heart. Obesity also results in dramatic changes in the release of adipokines, such as leptin and adiponectin, both of which have emerged as important regulators of cardiac energy metabolism. The link among obesity, cardiovascular disease, lipid metabolism, and adipokine signaling is complex and not well understood. However, optimizing cardiac energy metabolism in obese subjects may be one approach to preventing and treating cardiac dysfunction that can develop in this population. This review discusses what is presently known about the effects of obesity and the impact adipokines have on cardiac energy metabolism and insulin signaling. The clinical implications of obesity and energy metabolism on cardiac disease are also discussed. (Circ Res. 2007;101:335-347.)

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“…Leptin receptor deletion may also impair glucose utilization by the heart. Although some in vitro studies with cultured cardiomyocytes as well as whole animal studies have failed to demonstrate an increase in cardiac glucose uptake in response to leptin (20,37), studies in isolated Langendorff-perfused hearts have demonstrated that leptin increases glucose uptake (16). Therefore, loss of cardiac leptin receptor function may not only decrease fatty acid metabolism and delivery to the mitochondria but may also diminish the ability of the heart to increase glucose utilization to compensate for decreased fatty acid metabolism.…”

Section: Discussionmentioning

confidence: 99%

Cardiomyocyte-specific deletion of leptin receptors causes lethal heart failure in Cre-recombinase-mediated cardiotoxicity

Hall

Smith

Hall

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

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Although disruption of leptin signaling is associated with obesity as well as cardiac lipid accumulation and dysfunction, it has been difficult to separate the direct effects of leptin on the heart from those associated with the effects of leptin on body weight and fat mass. Using Cre-loxP recombinase technology, we developed tamoxifen-inducible, cardiomyocyte-specific leptin receptor-deficient mice to assess the role of leptin in regulating cardiac function. Cre recombinase activation in the heart resulted in transient reduction in left ventricular systolic function which recovered to normal levels by day 10. However, when cardiomyocyte leptin receptors were deleted in the setting of Cre recombinase-induced left ventricular dysfunction, irreversible lethal heart failure was observed in less than 10 days in all mice. Heart failure after leptin receptor deletion was associated with marked decreases of cardiac mitochondrial ATP, phosphorylated mammalian target of rapamycin (mTOR), and AMP-activated kinase (pAMPK). Our results demonstrate that specific deletion of cardiomyocyte leptin receptors, in the presence of increased Cre recombinase expression, causes lethal heart failure associated with decreased cardiac energy production. These observations indicate that leptin plays an important role in regulating cardiac function in the setting of cardiac stress caused by Cre-recombinase expression, likely through actions on cardiomyocyte energy metabolism.

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Insulin-Like Effect of Low-Dose Leptin on Glucose Transport in Langendorff Rat Hearts

Cited by 12 publications

References 36 publications

Leptin and cardiovascular diseases

Leptin and cardiovascular diseases

Cardiac Energy Metabolism in Obesity

Cardiomyocyte-specific deletion of leptin receptors causes lethal heart failure in Cre-recombinase-mediated cardiotoxicity

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