Endothelial cell (EC) glycocalyx (GCX) loss permits blood circulating particle infiltration of the vessel walls and leads to vascular dysfunction, atherosclerosis, and serious downstream cardiovascular events, motivating EC GCX regeneration to treat cardiovascular disease. This review discusses the benefits and drawbacks of current options for EC GCX regeneration and assessment. Existing pharmaceutical therapies are being explored for their applicability to EC GCX regeneration, while nutraceuticals are under development as primary EC GCX regeneration approaches, and novel therapies continue to emerge. Promotion of increased efficacy of these therapies by using novel targeted drug delivery approaches is proposed. In addition, development of intravital (and intravascular, if possible) detection tools for assessment of GCX health and GCX regeneration efficacy is recommended. The work presented in this review encourages continued development of GCX regeneration and detection approaches, which could lead to breakthrough solutions for addressing cardiovascular disease.

Previous results have demonstrated that short-term dieting attenuates neuronal inhibitory control on appetite measured with blood-oxygen-level-dependent (BOLD) responses to a food cue task. Because recent studies have suggested that functional connectivity measured during the task is strongly predictive of disease states, we sought to investigate the effect of weight loss on brain functional connectivity during the picture viewing task. Sixteen healthy obese (10F/6M, age 44.4±8 years, BMI 32.7±2) and 9 type 2 diabetes (T2DM) obese subjects (5F/4M, age 48±9, BMI 33.9±2) underwent functional MRI (fMRI) before and after an 8-week low-calorie diet. Brain connectivity (BOLD) was recorded while subjects viewed preselected images (high-calorie food, low-calorie food, and non-food). Participants lost 2.9±2.8 kg (p<0.05) weight after the diet. Using intrinsic connectivity distribution (ICD) analysis, there was a significant diet effect (p< 0.01) in the inferior pons, hypothalamus, and inferior medial hippocampus across all subjects. Diet by group interaction in ICD (p <0.001) was observed in the inferior anterior amygdala, inferior medial hippocampus, and hypothalamus, brain regions involved in the modulation of emotion and glucose metabolism. These results highlight the adaptive nature of neuronal control on diet and provide novel evidence for a variable nature of inhibitory neuronal adaptions in metabolic diseases. Disclosure C. Watt: None. T.K. Stanley: None. C. Lacadie: None. K.W.Y. Lam: None. M. Savoye: None. R. Sinha: None. T. Constable: None. D. Seo: None. J.J. Hwang: Research Support; Self; General Electric. R. Belfort-DeAguiar: Research Support; Self; Silver Palate Kitches. Funding National Institute of Diabetes and Digestive and Kidney Diseases (P30DK045735, K23 DK098286-02, R01DK020495); National Institutes of Health (UL1TR001863)

Poor sleep quality has been associated with increased risk of metabolic syndrome and type 2 diabetes as well as acceleration of neurodegenerative diseases. In rodents, sleep restriction decreases glucose transport into the brain via downregulation of GLUT1, the primary glucose transporter at the blood-brain barrier. However, little is known about the association between sleep quality and glucose transport and metabolism in the human brain. In this exploratory analysis, we quantified cerebral glucose levels amongst individuals with good and poor sleep quality as defined by the widely used and well-validated Pittsburgh Sleep Quality Index (PSQI), which assesses 7 different components of sleep quality over a 1 month time period (PSQI≥5 = Poor sleep; PSQI<5 = Good sleep). Twelve healthy subjects completed the PSQI questionnaire. Eight (6F, age 27.6 ± 5.7, BMI 26.6 ± 8.2 kg/m2, HgbA1c 5.4 ± 0.2%) had good and 4 (2F, age 29.5± 2.4, BMI 27.8 ± 6.5 kg/m2, HgbA1c 5.2 ± 0.2%) had poor sleep. All subjects underwent 13C magnetic resonance spectroscopy brain scanning at 4 Tesla during a 2-hour hyperglycemic clamp (plasma glucose target ∼180 mg/dl) to measure absolute cerebral glucose levels as part of a larger study to investigate obesity and cerebral glucose metabolism. There were no differences in age, BMI, or HbA1c levels between groups with good and poor sleep. Individuals with good sleep had 63% higher absolute cerebral glucose levels at steady state compared to those with poor sleep (3.4 ± 0.7 mmol/L vs. 2.1 ± 0.9 mmol/L, p=.017). Higher PSQI scores correlated with lower absolute cerebral glucose levels (r= -0.725, p=0.008, PSQI for all subjects (mean±SD) = 4 ± 2). In this pilot and exploratory study, individuals with poor sleep quality have significantly lower absolute cerebral glucose levels, which suggests an association between poor sleep and altered cerebral glucose transport and/or metabolism. These findings may have wide-ranging implications for understanding the effects of sleep on brain function. Disclosure T.K. Stanley: None. F. Gunawan: None. N.S. Redeker: None. L. Jiang: None. A. Coppoli: None. D.L. Rothman: None. G.F. Mason: None. J. Hwang: Research Support; Self; General Electric. Funding American Diabetes Association (1-17-ICTS-013 to J.H.); National Institutes of Health (1R03DK121048)