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Single-Molecule Imaging of Membrane Proteins on Vascular Endothelial Cells.
Park, J, Jin, S, Jang, J, Seo, D
Journal of lipid and atherosclerosis. 2023;(1):58-72
Abstract
Transporting substances such as gases, nutrients, waste, and cells is the primary function of blood vessels. Vascular cells use membrane proteins to perform crucial endothelial functions, including molecular transport, immune cell infiltration, and angiogenesis. A thorough understanding of these membrane receptors from a clinical perspective is warranted to gain insights into the pathogenesis of vascular diseases and to develop effective methods for drug delivery through the vascular endothelium. This review summarizes state-of-the-art single-molecule imaging techniques, such as super-resolution microscopy, single-molecule tracking, and protein-protein interaction analysis, for observing and studying membrane proteins. Furthermore, recent single-molecule studies of membrane proteins such as cadherins, integrins, caveolins, transferrin receptors, vesicle-associated protein-1, and vascular endothelial growth factor receptor are discussed.
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Stress-level glucocorticoids increase fasting hunger and decrease cerebral blood flow in regions regulating eating.
Bini, J, Parikh, L, Lacadie, C, Hwang, JJ, Shah, S, Rosenberg, SB, Seo, D, Lam, K, Hamza, M, De Aguiar, RB, et al
NeuroImage. Clinical. 2022;:103202
Abstract
CONTEXT The neural regulation of appetite and energy homeostasis significantly overlaps with the neurobiology of stress. Frequent exposure to repeated acute stressors may cause increased allostatic load and subsequent dysregulation of the cortico-limbic striatal system leading to inefficient integration of postprandial homeostatic and hedonic signals. It is therefore important to understand the neural mechanisms by which stress generates alterations in appetite that may drive weight gain. OBJECTIVE To determine glucocorticoid effects on metabolic, neural and behavioral factors that may underlie the association between glucocorticoids, appetite and obesity risk. METHODS A randomized double-blind cross-over design of overnight infusion of hydrocortisone or saline followed by a fasting morning perfusion magnetic resonance imaging to assess regional cerebral blood flow (CBF) was completed. Visual Analog Scale (VAS) hunger, cortisol and metabolic hormones were also measured. RESULTS Hydrocortisone relative to saline significantly decreased whole brain voxel based CBF responses in the hypothalamus and related cortico-striatal-limbic regions. Hydrocortisone significantly increased hunger VAS pre-scan, insulin, glucose and leptin, but not other metabolic hormones versus saline CBF groups. Hydrocortisone related increases in hunger were predicted by less reduction of CBF (hydrocortisone minus saline) in the medial OFC, medial brainstem and thalamus, left primary sensory cortex and right superior and medial temporal gyrus. Hunger ratings were also positively associated with plasma insulin on hydrocortisone but not saline day. CONCLUSIONS Increased glucocorticoids at levels akin to those experienced during psychological stress, result in increased fasting hunger and decreased regional cerebral blood flow in a distinct brain network of prefrontal, emotional, reward, motivation, sensory and homeostatic regions that underlie control of food intake.
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Efficacy and safety of Panax ginseng berry extract on glycemic control: A 12-wk randomized, double-blind, and placebo-controlled clinical trial.
Choi, HS, Kim, S, Kim, MJ, Kim, MS, Kim, J, Park, CW, Seo, D, Shin, SS, Oh, SW
Journal of ginseng research. 2018;(1):90-97
Abstract
BACKGROUND Antihyperglycemic effects of Panax ginseng berry have never been explored in humans. The aims of this study were to assess the efficacy and safety of a 12-wk treatment with ginseng berry extract in participants with a fasting glucose level between 100 mg/dL and 140 mg/dL. METHODS This study was a 12-wk, randomized, double-blind, placebo-controlled clinical trial. A total of 72 participants were randomly allocated to two groups of either ginseng berry extract or placebo, and 63 participants completed the study. The parameters related to glucose metabolism were assessed. RESULTS Although the present study failed to show significant antihyperglycemic effects of ginseng berry extract on the parameters related to blood glucose and lipid metabolism in the total study population, it demonstrated that ginseng berry extract could significantly decrease serum concentration of fasting glucose by 3.7% (p = 0.035), postprandial glucose at 60 min during 75 g oral glucose tolerance test by 10.7% (p = 0.006), and the area under the curve for glucose by 7.7% (p = 0.024) in those with fasting glucose level of 110 mg/dL or higher, while the placebo group did not exhibit a statistically significant decrease. Safety profiles were not different between the two groups. CONCLUSION The present study suggests that ginseng berry extract has the potential to improve glucose metabolism in human, especially in those with fasting glucose level of 110 mg/dL or higher. For a more meaningful benefit, further research in people with higher blood glucose levels is required.
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Humans with obesity have disordered brain responses to food images during physiological hyperglycemia.
Belfort-DeAguiar, R, Seo, D, Lacadie, C, Naik, S, Schmidt, C, Lam, W, Hwang, J, Constable, T, Sinha, R, Sherwin, RS
American journal of physiology. Endocrinology and metabolism. 2018;(5):E522-E529
Abstract
Blood glucose levels influence brain regulation of food intake. This study assessed the effect of mild physiological hyperglycemia on brain response to food cues in individuals with obesity (OB) versus normal weight individuals (NW). Brain responses in 10 OB and 10 NW nondiabetic healthy adults [body mass index: 34 (3) vs. 23 (2) kg/m2, means (SD), P < 0.0001] were measured with functional MRI (blood oxygen level-dependent contrast) in combination with a two-step normoglycemic-hyperglycemic clamp. Participants were shown food and nonfood images during normoglycemia (~95 mg/dl) and hyperglycemia (~130 mg/dl). Plasma glucose levels were comparable in both groups during the two-step clamp ( P = not significant). Insulin and leptin levels were higher in the OB group compared with NW, whereas ghrelin levels were lower (all P < 0.05). During hyperglycemia, insula activity showed a group-by-glucose level effect. When compared with normoglycemia, hyperglycemia resulted in decreased activity in the hypothalamus and putamen in response to food images ( P < 0.001) in the NW group, whereas the OB group exhibited increased activity in insula, putamen, and anterior and dorsolateral prefrontal cortex (aPFC/dlPFC; P < 0.001). These data suggest that OB, compared with NW, appears to have disruption of brain responses to food cues during hyperglycemia, with reduced insula response in NW but increased insula response in OB, an area involved in food perception and interoception. In a post hoc analysis, brain activity in obesity appears to be associated with dysregulated motivation (striatum) and inappropriate self-control (aPFC/dlPFC) to food cues during hyperglycemia. Hyperstimulation for food and insensitivity to internal homeostatic signals may favor food consumption to possibly play a role in the pathogenesis of obesity.
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Circulating glucose levels modulate neural control of desire for high-calorie foods in humans.
Page, KA, Seo, D, Belfort-DeAguiar, R, Lacadie, C, Dzuira, J, Naik, S, Amarnath, S, Constable, RT, Sherwin, RS, Sinha, R
The Journal of clinical investigation. 2011;121(10):4161-9
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Plain language summary
Glucose is an important fuel source for the brain. Specialised sensors in brain areas such as the hypothalamus, hindbrain and forebrain are essential for optimal blood glucose control and feeding. Low blood glucose results in hunger, although the specific neurological mechanisms causing this drive for food under these conditions is unclear. This trial performed functional MRI (fMRI) scans of 14 healthy non-obese (9) and obese (5) subjects in a mild low or normal blood glucose state. The study found that low blood sugar increases the activation of the reward and motivation regions of the brain (the hypothalamus, insula and striatum). It also found that circulating glucose levels interact with external food cues (i.e. the presence of food), stimulate the reward related brain regions and motivate an individual to eat high-calorie foods. In normal weight subjects, the pre-frontal cortex (PFC) (the brain region known for impulse control) was stimulated under normal blood sugar levels and caused less interest in food stimuli. Interestingly, obese subjects under normal blood sugar levels did not see this PFC stimulation. The authors conclude that this may contribute to overeating and a preference for high-calorie foods in obese people, which is worsened in low blood glucose conditions.
Abstract
Obesity is a worldwide epidemic resulting in part from the ubiquity of high-calorie foods and food images. Whether obese and nonobese individuals regulate their desire to consume high-calorie foods differently is not clear. We set out to investigate the hypothesis that circulating levels of glucose, the primary fuel source for the brain, influence brain regions that regulate the motivation to consume high-calorie foods. Using functional MRI (fMRI) combined with a stepped hyperinsulinemic euglycemic-hypoglycemic clamp and behavioral measures of interest in food, we have shown here that mild hypoglycemia preferentially activates limbic-striatal brain regions in response to food cues to produce a greater desire for high-calorie foods. In contrast, euglycemia preferentially activated the medial prefrontal cortex and resulted in less interest in food stimuli. Indeed, higher circulating glucose levels predicted greater medial prefrontal cortex activation, and this response was absent in obese subjects. These findings demonstrate that circulating glucose modulates neural stimulatory and inhibitory control over food motivation and suggest that this glucose-linked restraining influence is lost in obesity. Strategies that temper postprandial reductions in glucose levels might reduce the risk of overeating, particularly in environments inundated with visual cues of high-calorie foods.