Abstract
Obesity is one of the major risk factors for cardiovascular diseases and its prevalence is increasing in all age groups, with the biggest impact observed in middle-aged and older adults. A critical mechanism by which obesity promotes vascular pathologies in these patients involves impairment of endothelial function. While endothelial dysfunction in large vessels promotes atherogenesis, obesity-induced microvascular endothelial dysfunction impairs organ perfusion and thereby is causally related to the pathogenesis of ischemic heart disease, chronic kidney disease, intermittent claudication, exercise intolerance, and exacerbates cognitive decline in aging. Reduction of weight via calorie-based diet and exercise in animal models of obesity results in significant improvement of endothelial function both in large vessels and in the microcirculation, primarily due to attenuation of oxidative stress and inflammation. Clinical data on the protective effects of weight loss on endothelial function is limited to studies of flow-mediated dilation assessed in brachial arteries. Currently, there is no guideline on testing the effects of different weight management strategies on microvascular endothelial function in obese patients. Here, we provide proof-of-concept that weight loss-induced improvement of microvascular endothelial function can be reliably assessed in the setting of a geriatric outpatient clinic using a fast, reproducible, non-invasive method: laser speckle contrast imaging-based measurement of endothelium-dependent microvascular responses during post-occlusive reactive hyperemia tests. Our study also provides initial evidence that short-term weight loss induced by consumption of a low-carbohydrate low-calorie diet can reverse microvascular endothelial dysfunction associated with obesity.
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This work was supported by the National Institutes of Health (NIH) Grants R01-AT-006526, R01-AG047879, R01-AG038747, and R01-NS056218, the Geroscience Training Program in Oklahoma (NIH Grant T32-AG-052363), the Oklahoma Nathan Shock Center (NIH Grant 3-P30-AG050911-02S1), the Oklahoma Shared Clinical and Translational Resources (NIH Grant U54-GM-104938), the Oklahoma Center for the Advancement of Science and Technology (HR17-070), the College of Medicine Alumni Association, the Presbyterian Health Foundation, and the EU-funded grant EFOP-3.6.1-16-2016-00008. The paper was published as part of the “Translational Geroscience” initiative of the Journal of the American Aging Association (Ashpole et al. 2017; Bennis et al. 2017; Callisaya et al. 2017; Csiszar et al. 2017; Deepa et al. 2017; Grimmig et al. 2017; Hancock et al. 2017; Kane et al. 2017; Kim et al. 2017; Konopka et al. 2017; Liu et al. 2017; Meschiari et al. 2017; Perrott et al. 2017; Podlutsky et al. 2017; Shobin et al. 2017; Sierra and Kohanski 2017; Tarantini et al. 2017a; Tarantini et al. 2017b; Tenk et al. 2017; Tucsek et al. 2017; Ungvari et al. 2017a, b ; Urfer et al. 2017a, b).
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Csipo, T., Fulop, G.A., Lipecz, A. et al. Short-term weight loss reverses obesity-induced microvascular endothelial dysfunction. GeroScience 40, 337–346 (2018). https://doi.org/10.1007/s11357-018-0028-9
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DOI: https://doi.org/10.1007/s11357-018-0028-9