Publications by authors named "Shannon Bevans-Fonti"

Mismatch between CO production (Vco) and respiration underlies the pathogenesis of obesity hypoventilation. Leptin-mediated CNS pathways stimulate both metabolism and breathing, but interactions between these functions remain elusive. We hypothesized that LEPR+ neurons of the dorsomedial hypothalamus (DMH) regulate metabolism and breathing in obesity.

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Obese asthma is a unique phenotype of asthma characterized by non-allergic airway hyperresponsiveness (AHR) and inflammation which responds poorly to standard asthma therapy. Metformin is an oral hypoglycemic drug with insulin-sensitizing and anti-inflammatory properties. The objective of the current study was to test the effect of metformin on AHR in a mouse model of diet-induced obesity (DIO).

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We have previously shown that high fat diet (HFD) for 2 weeks increases airway hyperresponsiveness (AHR) to methacholine challenge in C57BL/6J mice in association with an increase in IL-1β levels in lung tissue. We hypothesize that obesity increases AHR via the IL-1β mechanism, which can be prevented by caloric restriction and IL-1β blockade. In this study, we fed C57BL/6J mice for 8 weeks with several hypercaloric diets, including HFD, HFD supplemented with fructose, high trans-fat diet (HTFD) supplemented with fructose, either ad libitum or restricting their food intake to match body weight to the mice on a chow diet (CD).

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Rationale: Leptin treats upper airway obstruction and alveolar hypoventilation in leptin-deficient ob/ob mice. However, obese humans and mice with diet-induced obesity (DIO) are resistant to leptin because of poor permeability of the blood-brain barrier. We propose that intranasal leptin will bypass leptin resistance and treat sleep-disordered breathing in obesity.

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Article Synopsis
  • The study investigated how a high fat diet (HFD) influences airway hyperresponsiveness (AHR) in mice, comparing results with a regular chow diet over two weeks.
  • While body weight increased by 11% on HFD, it did not change baseline respiratory resistance but significantly heightened airway responses to methacholine, with a notable 40.5% increase at the highest concentration.
  • The HFD led to a substantial increase in IL-1β expression and secretion in lung tissue, indicating a link between high fat intake and inflammatory responses in the airways, despite no changes in bronchoalveolar lavage or other measured factors.
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Obstructive sleep apnea is associated with type 2 diabetes. We have previously developed a mouse model of intermittent hypoxia (IH) mimicking oxyhemoglobin desaturations in patients with sleep apnea and have shown that IH increases fasting glucose, hepatic glucose output, and plasma catecholamines. We hypothesize that adrenal medulla modulates glucose responses to IH and that such responses can be prevented by adrenal medullectomy.

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Background: Obstructive sleep apnea (OSA) is associated with the progression of non-alcoholic fatty liver disease (NAFLD) to steatohepatitis and fibrosis. This progression correlates with the severity of OSA-associated hypoxia. In mice with diet induced obesity, hepatic steatosis leads to liver tissue hypoxia, which worsens with exposure to intermittent hypoxia.

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Unlabelled: Hypoxia-inducible factor-1α (HIF-1α) in adipose tissue is known to promote obesity. We hypothesized that HIF-1α interferes with brown fat thermogenesis, thus decreasing energy expenditure. To test this hypothesis, we compared transgenic mice constitutively expressing HIF-1α in adipose tissues (HIF-1α++) at usual temperature (22 °C), where brown fat is somewhat active, or at thermoneutrality (30 °C), where brown fat is minimally active.

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Obstructive sleep apnea is associated with high cardiovascular morbidity and mortality. Intermittent hypoxia of obstructive sleep apnea is implicated in the development and progression of insulin resistance and atherosclerosis, which have been attributed to systemic inflammation. Intermittent hypoxia leads to pro-inflammatory gene up-regulation in cell culture, but the effects of intermittent hypoxia on gene expression in humans have not been elucidated.

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Study Objectives: Obstructive sleep apnea (OSA) is associated with the progression of nonalcoholic fatty liver disease (NAFLD). We hypothesized that the hypoxia of OSA increases hepatic production of lysyl oxidase (LOX), an enzyme that cross-links collagen, and that LOX may serve as a biomarker of hepatic fibrosis.

Design: Thirty-five patients with severe obesity underwent liver biopsy, polysomnography, and serum LOX testing.

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Obstructive sleep apnea causes intermittent hypoxia (IH) during sleep and is associated with dysregulation of glucose metabolism. We developed a novel model of clinically realistic IH in mice to test the hypothesis that IH causes hyperglycemia, glucose intolerance, and insulin resistance via activation of the sympathetic nervous system. Mice were exposed to acute hypoxia of graded severity (21, 14, 10, and 7% O2) or to IH of graded frequency [oxygen desaturation index (ODI) of 0, 15, 30, or 60, SpO2 nadir 80%] for 30 min to measure levels of glucose fatty acids, glycerol, insulin, and lactate.

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Obstructive sleep apnea causes intermittent hypoxia (IH) and is associated with insulin resistance and type 2 diabetes. IH increases plasma catecholamine levels, which may increase insulin resistance and suppress insulin secretion. The objective of this study was to determine if adrenal medullectomy (MED) prevents metabolic dysfunction in IH.

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Obstructive sleep apnea causes chronic intermittent hypoxia (IH) and is associated with impaired glucose metabolism, but mechanisms are unknown. Carotid bodies orchestrate physiological responses to hypoxemia by activating the sympathetic nervous system. Therefore, we hypothesized that carotid body denervation would abolish glucose intolerance and insulin resistance induced by chronic IH.

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Article Synopsis
  • Obstructive sleep apnea may lead to dyslipidemia and atherosclerosis by causing chronic intermittent hypoxia (CIH), which affects lipid metabolism by increasing levels of angiopoietin-like 4 (Angptl4) in adipose tissue.
  • The study found that exposure to CIH in mice raised Angptl4 levels, inhibited lipoprotein lipase activity, and increased plasma triglycerides and atherosclerotic plaque size, effects that were reversed by a neutralizing antibody.
  • Additionally, the role of hypoxia-inducible factor-1 (HIF-1) was significant, as its overexpression in adipose tissue resulted in similar metabolic issues, indicating that HIF-1 and Ang
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Obesity is associated with tissue hypoxia and the up-regulation of hypoxia inducible factor 1 alpha (HIF-1α). Prior studies in transgenic mice have shown that HIF-1α plays a role in the metabolic dysfunction associated with obesity. Therefore, we hypothesized that, after the development of diet-induced obesity (DIO), metabolic function could be improved by administration of HIF-1α antisense oligonucleotides (ASO).

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Obstructive sleep apnea (OSA) induces intermittent hypoxia (IH) during sleep and is associated with elevated triglycerides (TG). We previously demonstrated that mice exposed to chronic IH develop elevated TG. We now hypothesize that a single exposure to acute hypoxia also increases TG due to the stimulation of free fatty acid (FFA) mobilization from white adipose tissue (WAT), resulting in increased hepatic TG synthesis and secretion.

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Obesity causes insulin resistance (IR) and nonalcoholic fatty liver disease (NAFLD), but the relative contribution of sleep apnea is debatable. The main aim of this study is to evaluate the effects of chronic intermittent hypoxia (CIH), a hallmark of sleep apnea, on IR and NAFLD in lean mice and mice with diet-induced obesity (DIO). Mice (C57BL/6J), 6-8 weeks of age were fed a high fat (n = 18) or regular (n = 16) diet for 12 weeks and then exposed to CIH or control conditions (room air) for 4 weeks.

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Obstructive sleep apnea (OSA) causes intermittent hypoxia (IH) during sleep. Both obesity and OSA are associated with insulin resistance and systemic inflammation, which may be attributable to tissue hypoxia. We hypothesized that a pattern of hypoxic exposure determines both oxygen profiles in peripheral tissues and systemic metabolic outcomes, and that obesity has a modifying effect.

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Aims: Delayed lipoprotein clearance is associated with atherosclerosis. This study examined whether chronic intermittent hypoxia (CIH), a hallmark of obstructive sleep apnoea (OSA), can lead to hyperlipidaemia by inhibiting clearance of triglyceride rich lipoproteins (TRLP).

Methods And Results: Male C57BL/6J mice on high-cholesterol diet were exposed to 4 weeks of CIH or chronic intermittent air (control).

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Article Synopsis
  • The study investigates how surgical weight loss impacts inflammatory biomarkers related to sleep apnea, hypothesizing that weight loss would reduce sleep apnea severity and proinflammatory cytokine levels.
  • 23 morbidly obese adults were assessed before and after bariatric surgery, showing significant decreases in body mass index (BMI), apnea-hypopnea index (AHI), and several inflammatory markers, while other biomarkers like ghrelin and adiponectin increased.
  • Results indicate that the decrease in the biomarker sTNFαR2 is significantly linked to the improvement of sleep apnea post-surgery, suggesting it could be a reliable indicator of sleep apnea across different body weights.
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  • * Adult mice were exposed to chronic IH for three months, demonstrating significant increases in lung volumes and surface area without changes in the size of the airspaces; the study suggests that IH positively impacts lung growth.
  • * Findings showed a marked increase in cellular proliferation in lung tissue, particularly in type II alveolar cells, while apoptosis rates remained unchanged, indicating that IH promotes lung development through enhanced cellular activity and activation of growth-related gene pathways.
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  • The study explores how obstructive sleep apnea (OSA) may impact glucose regulation and contribute to prediabetes and diabetes, focusing on the mechanisms involved and biomarker profiles in obese adults.
  • Researchers examined 45 severely obese adults through various measurements, including blood tests, to assess the relationship between OSA severity and insulin sensitivity/beta-cell function.
  • Results indicated that OSA severity is linked to reduced insulin sensitivity and increased basal beta-cell function, with distinct biomarker profiles for normal and impaired glucose metabolism, suggesting a potential risk for beta-cell exhaustion over time.
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  • Obstructive sleep apnea can lead to vascular issues due to intermittent hypoxia (IH), which activates specific proinflammatory genes more effectively than sustained hypoxia (SH).
  • In experiments comparing IH and SH in human aortic endothelial cells, both conditions increased proinflammatory gene expression and elevated cytokine levels, particularly IL-8 and IL-6, but IH showed a greater increase in IL-8 mRNA levels.
  • Both IH and SH conditions also promoted antioxidant gene expression, with some genes behaving similarly across both types of hypoxia, indicating a complex response in endothelial cells to these different oxygen levels.
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Objective: Obstructive sleep apnea causes intermittent hypoxia (IH) and is associated with increased cardiovascular mortality. This increased risk may be attributable to more extensive or unstable atherosclerotic plaques in subjects with OSA. We studied the effect of chronic IH in atherosclerosis-prone mice.

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