Abstract
A wealth of investigations, ranging from clinical and animal model studies to in vitro analyses, have generated great interest in the cardiovascular effects of leptin. Accordingly, many studies have examined the contribution of leptin to cardiac remodeling in heart failure and whether the effects of leptin on metabolism, apoptosis, extracellular matrix remodeling, and hypertrophy could explain the so-called obesity paradox. Furthermore, obesity and hyperleptinemia have often been associated with hypertension, and regulation of sympathetic tone or direct effects of leptin on contributors such as atherosclerosis, endothelial dysfunction, and thrombosis have been documented. Unfortunately, translating basic research studies in vitro, or in animal models, to human physiology has proven difficult. The degree of leptin resistance in obesity is one intriguing issue that must be resolved. Furthermore, the importance of autocrine and paracrine effects of leptin derived from the heart and perivascular adipose tissue must be further studied. Carefully planned and executed research to conclusively establish distinct effects of leptin on the cardiovascular system in normal and diseased states will be essential to harness any therapeutic potential associated with leptin's effects.
Key Points
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Leptin regulates various cardiovascular effects, yet many paradoxical observations have been reported and several controversies remain
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Reasons for these discrepancies may include the temporal nature of cardiovascular disease, actual leptin concentration examined, and the degree of crosstalk with other cardioregulatory factors
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Leptin resistance is thought to develop in obese individuals, yet may be selective to only a subset of the physiological effects of leptin
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Excess or inadequate leptin signaling are likely to result in unfavorable outcomes, and the maintenance of homeostatic leptin effects may be a beneficial treatment strategy
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The myocardium and perivascular adipose tissue are known sources of leptin, which might exert important autocrine and paracrine effects
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The author's work is funded by the Canadian Institutes of Health Research, Heart & Stroke Foundation of Canada, Canadian Diabetes Association and Korean Ministry of Education Science and Technology. Figures are intended to convey general conclusions from published literature and exceptions may exist.
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Sweeney, G. Cardiovascular effects of leptin. Nat Rev Cardiol 7, 22–29 (2010). https://doi.org/10.1038/nrcardio.2009.224
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DOI: https://doi.org/10.1038/nrcardio.2009.224
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