Patients with obstructive sleep apnea (OSA) and metabolic dysfunction associated steatotic liver disease (MASLD) frequently overlap due to the high prevalence of obesity. This translational study aimed to identify cytokines linking these conditions, beginning with an analysis of fatty liver in mice. Serum cytokine levels upregulated in the fatty liver mice were subsequently examined in human OSA serum samples.

Mice were fed a high-fat diet to induce fatty liver. Liver proteins were analyzed using cytokine arrays. Serum samples from seventy (70) OSA patients (with 20 non-MASLD and 50 MASLD, pre- and 6-month post-continuous positive airway pressure [CPAP] therapy) were analyzed for the cytokines identified in the mouse experiment using enzyme-linked immunosorbent assays.

Four platelet-activation chemokines/cytokines (CCL5/RANTES, P-selectin, CXCL4/PF4, and CXCL5/LIX) were upregulated in mice with fatty liver. While serum levels of these factors were not significantly higher in MASLD-OSA compared to non-MASLD-OSA patients, their levels significantly decreased 6 months after the initiation of CPAP therapy, along with a reduction in mean platelet volume. CPAP compliance was significantly associated with a reduction in CCL5 levels. Additionally, a decrease in ALT levels following 6 months of CPAP therapy was significantly associated with CPAP compliance in MASLD-OSA patients.

While platelet-activation cytokines were not directly implicated in liver injury in MASLD-OSA patients, they decreased with CPAP therapy. CPAP compliance may play a key role in ALT reduction in MASLD-OSA patients independently of body weight changes. CCL5/RANTES may be indirectly associated with liver injury in MASLD-OSA, potentially induced through intermittent hypoxia.

A dysregulated circadian system is independently associated with both Obstructive Sleep Apnea (OSA) and cardiovascular disease (CVD). OSA and CVD coexistence is often seen in patients with prolonged untreated OSA. However, the role of circadian dysregulation in their relationship is unclear. Half of the human genes, associated biological pathways, and physiological functions exhibit circadian rhythms, including blood pressure and heart rate regulation. Mechanisms related to circadian dysregulation and heart function are potentially involved in the coexistence of OSA and CVD. In this article, we provide a comprehensive overview of circadian dysregulation in OSA and associated CVD. We also discuss feasible animal models and new avenues for future research to understand their relationship. Oxygen-sensing pathways, inflammation, dysregulation of cardiovascular processes, oxidative stress, metabolic regulation, hormone signaling, and epigenetics are potential clock-regulated mechanisms connecting OSA and CVD.

Obstructive sleep apnea syndrome (OSAS) is associated with the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Tripartite motif containing 24 (TRIM24) deficiency causes hepatic lipid accumulation and hepatitis. However, the expression, function, and mechanism of TRIM24 in OSAS and MASLD remain unclear. Herein, an OSAS and MASLD mouse model was established by intermittent hypoxia (IH) and high-fat diet. IH- and 1% free fatty acid-induced mouse liver cells served as an in vitro model. TRIM24 and HIF1A were up-regulated under the IH condition. HIF1A enhanced the transcriptional activity of TRIM24. Overexpression of TRIM24 reduced hepatic lipid accumulation, decreased serum levels of total cholesterol, triglyceride, and low-density lipoprotein cholesterol, and increased serum levels of high-density lipoprotein cholesterol in OSAS and MASLD mice. Additionally, overexpression of TRIM24 alleviated inflammation and oxidative stress, and modulated aberrant lipid metabolism. Mechanically, TRIM24 up-regulated the expression of ORM2, a key regulator of hepatic lipogenesis, by binding to H3K27ac and recruiting retinoic acid receptor-α to ORM2 promoter. The cell rescue model was used to verify that ORM2 mediated the hepatoprotective effects of TRIM24. The current study reveals the important role of TRIM24 as an epigenetic coregulator of transcription in OSAS and MASLD, providing additional insights into understanding the pathogenesis and preventing the development of OSAS and MASLD.

Patients with obstructive sleep apnea (OSA) experience insulin resistance and its clinical consequences, including hypertriglyceridemia, reduced high density lipoprotein-associated cholesterol (HDL-c), visceral adiposity, hepatic steatosis, increased epicardial fat thickness, essential hypertension, glucose intolerance, increased risk for type 2 diabetes, chronic kidney disease, subclinical vascular damage, and increased risk for cardiovascular events. Obesity is a major contributor to OSA. The prevalence of OSA is almost universal among patients with severe obesity undergoing bariatric surgery. However, insulin resistance and its clinical complications occur in OSA patients irrespective of general obesity (body mass index). In OSA patients, apnea episodes during sleep induce oxyhemoglobin desaturation and tissue hypoxia. Insulin resistance is an adaptive response to tissue hypoxia and develops in conditions with limited tissue oxygen supply, including healthy subjects exposed to hypobaric hypoxia (high altitude) and OSA patients. Indicators of oxyhemoglobin desaturation have been robustly and independently linked to insulin resistance and its clinical manifestations in patients with OSA. Insulin resistance mediates the elevated rate of type 2 diabetes, chronic kidney disease, and cardiovascular disease unexplained with traditional cardiovascular risk factors present in OSA patients. Pathophysiological processes underlying hypoxia-induced insulin resistance involve hypoxia inducible factor-1 upregulation and peroxisome proliferator-activated receptor-gamma (PPAR- γ ) downregulation. In human adipose tissue, PPAR- γ activity promotes glucose transport into adipocytes, lipid droplet biogenesis, and whole-body insulin sensitivity. Silencing of PPAR- γ in the adipose tissue reduces glucose uptake and fat accumulation into adipocytes and promotes insulin resistance. In conclusion, tissue hypoxia drives insulin resistance and its clinical consequences in patients with OSA, regardless of body mass index.

Obesity and metabolic syndrome affect the majority of the US population. Patients with obesity are at increased risk of developing type 2 diabetes (T2DM), obstructive sleep apnea (OSA), and metabolic dysfunction-associated steatotic liver disease (MASLD), each of which carry the risk of further complications if left untreated and lead to adverse outcomes. The rising prevalence of obesity and its comorbidities has led to increased mortality, decreased quality of life, and rising healthcare expenditures. This phenomenon has resulted in the intensive investigation of exciting therapies for obesity over the past decade, including more treatments that are still in the pipeline. In our present report, we aim to solidify the relationships among obesity, T2DM, OSA, and MASLD through a comprehensive review of current research. We also provide an overview of the surgical and pharmacologic treatment classes that target these relationships, namely bariatric surgery, the glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon receptor agonists.

Observational studies indicate that sleep apnea is associated with non-alcoholic fatty liver disease (NAFLD) and its related metabolic features, independent of confounding factors including obesity. However, the causal relationships remain to be determined.

Univariable and multivariable Mendelian randomization (MR) analyses were performed to investigate the causal relationship between sleep apnea and NAFLD, along with its typical features including liver function, glycemic traits and lipid profiles. Summary-level data for sleep apnea were obtained from the Finngen consortium (33,423 cases and 307,648 controls). Summary-level data for NAFLD were available from a GWAS meta-analysis (8434 cases and 770,180 controls), and data for 12 NAFLD-related features from corresponding published GWASs. The inverse variance weighted (IVW) analysis was employed as the primary statistical method. Bidirectional MR and CAUSE analysis were conducted to avoid reverse causality and false positive findings.

In univariable MR analyses, we found evidence to support a causal effect of genetically predicted sleep apnea on NAFLD (OR = 1.50, 95% CI = 1.18-1.91) and HDL-C (β = -0.045, 95% CI = -0.090 to -0.001). In reverse MR, genetically predicted serum TG was associated with an increased risk of sleep apnea (OR = 1.07, 95% CI = 1.02-1.12), while genetically predicted HDL-C was associated with a decreased risk of sleep apnea (OR = 0.93, 95% CI = 0.89-0.98). After adjusting body mass index or educational attainment, none of these causal associations were retained. However, CAUSE method and MR analyses focusing on lipoprotein subfractions supported a causal effect of sleep apnea on HDL-C and HDL subfractions.

This MR study indicated that sleep apnea has no direct causal association with NAFLD, elevated liver enzymes and insulin resistance. Our results showed suggestive inverse associations of genetically predicted sleep apnea on HDL-C and HDL subfractions, indicating that both HDL-C levels and HDL function may be causally implicated in sleep apnea.

Sleep-disordered breathing (SDB) and non-alcoholic fatty liver disease (NAFLD) are both common comorbidities in obese patients. Structured weight loss programs are effective and can reduce the incidence and severity of obesity-related comorbidities. The objective of the present analysis is to test whether weight loss induced alleviation of SDB is a predictor for improvement of NAFLD.

Obese participants underwent a standardized non-surgical 3 months weight reduction program (800 kilocalories per day with low carbohydrate and fat content). Abdominal sonography for NAFLD (grade 0 to 3) and monitoring for SDB (defined as apnea-hypopnea index [AHI] ≥ 15/h) were performed at baseline and after 3 months. Alleviation of SDB was defined as a shift from AHI≥ 15/h to <15/h.

48 patients (48% female, age 42 ± 12 years, body-mass index 40.3 ± 8.1 kg/m2, AHI 14 ± 17/h, 85% NAFLD grade ≥1) participated in the weight loss program. In contrast to the no SDB group, in patients with SDB weight loss of 27.1 ±0 .9 kg (8.4 ± 2.8 kg/m2) after three months was paralleled by a reduction in AHI (-22 ± 17/h), prevalence of SDB (from 31% to 13%), and oxidized low-density lipoprotein (-13 ± 11 U/l). In individuals with preexisting SDB NAFLD grade improved more (2 versus 1, p<0.001) and was at a lower degree at 3 months than in those without SDB (0 versus 1, p = 0.015). In multivariable analysis models, SDB at baseline was associated with improvement of NAFLD grade (B 0.908; 95% CI 0.125, 1.691; p = 0.024), independently of age, sex, and BMI (each p>0.05, respectively). Decreasing BMI (B 0.16 [95%-CI 0.08; 0.23], p<0.001) and alleviation of SDB (B 0.90 [95%-CI 0.21; 1.58], p = 0.012) were independently associated with improvement of NAFLD grade.

Preexisting SDB and weight loss induced alleviation of SDB are predictors for improvement in NAFLD grade, independent of the extent of weight loss. SDB may contribute to the pathogenesis of NAFLD via SDB-induced oxidative stress and inflammation, but the causal mechanism remains unclear.

Obesity has been linked to non-alcoholic fatty liver disease (NAFLD), a widespread chronic liver ailment, as well as obstructive sleep apnea (OSA). The development of NAFLD is influenced by repeated intermittent hypoxia, a feature of OSA.

This systematic review (SR) investigated CENTRAL, PubMed, and EMBASE databases. The endpoint of this SR was to assess which OSA-related indicators could predict the presence of NAFLD and the effect of bariatric metabolic surgery (BMS) on improving OSA and NAFLD over time.

Compared to previous SRs published in 2013, 14 new publications were added to our SR, alongside studies conducted prior to 2013. The SR ultimately included 28 studies (18 cross-sectional and 10 cohort trials). In the majority of studies, significant correlations were observed between OSA, OSA-related outcomes, and NAFLD. However, the apnea-hypopnea index (AHI) alone proved to be an inadequate predictor of NAFLD. Instead, respiratory and metabolic changes were found to alleviate oxidative stress induced by hypoxemia. Six studies involved patients who underwent BMS, with one evaluating patients before and after BMS, revealing associations between increased OSA and NAFLD improvement following BMS. Six months after surgery, 100% of patients in the mild-to-moderate OSA group were free from fatty liver, and an 89% reduction was observed in the severe OSA group.

For the first time, BMS has been tested in treating both OSA and NAFLD pre and postoperative with positive results. Further research, ideally with histological and functional data, is needed to confirm these findings. The SR identified 14 distinct liver outcome tests; however, high heterogeneity and incomplete data precluded a meta-analysis. It is imperative to pay greater attention to the influence of OSA-related factors and uniformity in liver outcomes testing concerning NAFLD. To accomplish this, study designs should be enhanced by incorporating more comprehensive pre- and postoperative evaluations, extending follow-up periods, and employing a more consistent methodology for liver diagnosis in patients with obesity.

Both obstructive sleep apnea (OSA) and non-alcoholic fatty liver disease (NAFLD) are prevalent within obese individuals. We aimed to investigate the effects of intermittent hypoxia (IH), a clinical feature of OSA, on hepatic expression of fatty acid translocase (CD36) in relation to liver injury in lean and diet-induced obese mice.

Four-week-old male C57BL/6J mice were randomized to standard diet (SD) or high fat (HF) diet groups. At 13-week-old, all mice were exposed to either air or IH (IH30; thirty hypoxic episodes per hour) for four weeks. We assessed liver injury through lipid profile, oxidative and inflammatory stress, histological scoring and hepatic CD36 expression.

In lean mice, IH elevated serum and hepatic triglyceride and free fatty acid (FFA) levels, in line with upregulation of hepatic CD36 expression and myeloperoxidase (MPO)-positive cells in support of inflammatory infiltrates along with increase in serum malondialdehyde (MDA), C-X-C motif chemokine ligand 1(CXCL-1) and monocyte chemoattractant protein-1 (MCP-1). In diet-induced obese mice, an increase in hepatic alanine transaminase (ALT) activity, serum and hepatic levels of lipid parameters and inflammatory markers, serum MDA level, hepatic expressions of CD36 and α-smooth muscle actin (α-SMA), and MPO-positive cells was observed. IH potentiated hepatic ALT activity, serum CXCL-1 and hepatic interleukin-6 (IL-6), in line with inflammatory infiltrates, but paradoxically, reduced hepatic FFA level and hepatic CD36 expression, compared to obese mice without IH exposure. However, IH further augmented diet-induced liver steatosis and fibrosis as shown by histological scores.

This study contributes to support that IH featuring OSA may lead to liver injury via differential regulation of hepatic CD36 expression in lean and diet-induced obese mice.

Obstructive sleep apnea (OSA) is an independent risk factor for stroke. Furthermore, intracranial arterial calcification (IAC) has been validated as a marker for subclinical cerebrovascular disease. However, the relationship between OSA with IAC was less studied compared with its established association with coronary artery calcification. In this study, we aimed to investigate the association between the severity of OSA and the degree of IAC in hospitalized patients without preexisting cardiovascular disease.

This hospital-based observational study was conducted from June 1, 2017, to May 1, 2019. In total, 901 consecutive patients who underwent head computed tomography scans and portable sleep monitoring were included. On the basis of the apnea-hypopnea index (AHI), patients were divided into four OSA severity groups (normal: AHI <5/h; mild: 5≤ AHI <15/h; moderate: 15≤ AHI <30/h; severe: AHI ≥30/h). Associations of OSA with IAC scores were assessed by using multivariate logistic regression analysis.

Of the 901 patients, 484 (53.7%) were men; the mean (SD) age was 66.1 (10.0) years. The non-OSA group included 207 (23.0%) patients; mild OSA, 209 (23.2%); moderate OSA, 235 (26.1%); and severe OSA, 169 (18.8%). Mean IAC scores were higher in the severe OSA group compared with non-, mild, and moderate OSA groups (4.79 vs. 2.58; 4.79 vs. 2.94; 4.79 vs. 3.39; p < 0.001). Multivariate analysis adjusted for confounding factors revealed that only severe OSA was associated with a higher IAC score (odds ratio [OR]: 1.65; 95% confidence interval [CI]: 1.43-1.91; p < 0.001). In stratified analyses by BMI, among participants with a BMI <25 kg/m2, the positive association between AHI values and IAC scores was found in the moderate OSA group (OR: 1.23; 95% CI: 1.05, 1.43; p = 0.01) and the severe OSA group (OR: 1.96; 95% CI: 1.55, 2.48; p < 0.001). When stratified by gender, in women, the positive association was found in the moderate OSA group (adjusted OR: 1.21; 95% CI: 1.02-1.51; p = 0.016) and the severe OSA group (adjusted OR: 1.76; 95% CI: 1.36-2.25; p < 0.001). For the men group, a positive association between IAC scores and AHI was only observed in the severe OSA group.

These findings suggest that OSA, in particular severe OSA (AHI ≥30), is independently associated with higher IAC scores. Women and no-obesity individuals appeared more susceptible to adverse OSA-related subclinical cerebrovascular disease as measured by IAC scores.

Obstructive sleep apnea (OSA) is associated with metabolic dysfunction, including progression of nonalcoholic fatty liver disease (NAFLD). Chronic intermittent hypoxia (IH) as a model of OSA worsens hepatic steatosis and fibrosis in rodents with diet induced obesity. However, IH also causes weight loss, thus complicating attempts to co-model OSA and NAFLD. We sought to determine the effect of various durations of IH exposure on metabolic and liver-related outcomes in a murine NAFLD model. We hypothesized that longer IH duration would worsen the NAFLD phenotype.

Male C57BL/6J mice (n = 32) were fed a high trans-fat diet for 24 weeks, to induce NAFLD with severe steatohepatitis. Mice were exposed to an IH profile modeling severe OSA, for variable durations (0, 6, 12, or 18 weeks). Intraperitoneal glucose tolerance test was measured at baseline and at six-week intervals. Liver triglycerides, collagen and other markers of NAFLD were measured at sacrifice.

Mice exposed to IH for 12 weeks gained less weight (p = 0.023), and had lower liver weight (p = 0.008) relative to room air controls. These effects were not observed in the other IH groups. IH of longer duration transiently worsened glucose tolerance, but this effect was not seen in the groups exposed to shorter durations of IH. IH exposure for 12 or 18 weeks exacerbated liver fibrosis, with the largest increase in hepatic collagen observed in mice exposed to IH for 12 weeks.

Duration of IH significantly impacts clinically relevant outcomes in a NAFLD model, including body weight, fasting glucose, glucose tolerance, and liver fibrosis.

The association between sleep-disordered breathing (SDB) and sinusitis has been widely studied; however, research on SDB-related sleep problems and sinusitis are limited. This study aims to determine the relationship between SDB-related sleep problems, SDB symptom score, and sinusitis.

After the screening, data were analyzed from 3414 individuals (≥20 years) from the 2005-2006 National Health and Nutrition Examination Survey questionnaire. Data on snoring, daytime sleepiness, obstructive sleep apnea (snorting, gasping, or cessation of breathing while sleeping), and sleep duration were analyzed. The SDB symptom score was determined based on a summary of the scores of the above four parameters. Pearson chi-square test and logistic regression analysis were used in statistical analyses.

After adjusting for confounders, self-reported sinusitis was strongly correlated with frequent apneas (OR: 1.950; 95% CI: 1.349-2.219), excessive daytime sleepiness (OR: 1.880; 95% CI: 1.504-2.349), and frequent snoring (OR: 1.481; 95% CI: 1.097-2.000). Compared to an SDB symptom score of 0, the higher the SDB symptom score, the higher the risk of self-reported sinusitis. For the subgroup analyses, this association was significant in females and across ethnic groups.

In the United States, SDB is significantly associated with self-reported sinusitis in adults. In addition, our study suggests that patients with SDB should be aware of the risk of developing sinusitis.

The association between obstructive sleep apnea (OSA) and cancer risks gaining more and more attention. Data on the association between OSA and lung cancer risk are limited. This study is to investigate whether a link exists between low-dose computed tomography (LDCT) scanning of the chest findings, carcinoembryonic antigen (CEA) and OSA in patients suspected of OSA.

The cross-sectional study included patients aged 18 years or older who underwent continuous nocturnal polysomnography at our sleep center between February 2019 and November 2020. All subjects underwent chest LDCT and CEA. Patients with an apnea-hypopnea index (AHI) of ≥ 15/h were classified as clinically significant OSA group, whereas patients with an AHI < 15/h were classified as control group.

A total of 277 patients were enrolled in the study. 176 patients were categorized into the OSA group, while 101 patients were categorized into the control group. There is no relationship between any OSA-related parameter and presence of lung nodule or presence of ≥ 6 mm lung nodule in the binary logistic regression analysis. OSA group demonstrated a significant higher value of CEA than control group. Stepwise multiple linear regression analysis showed that lowest O₂ saturation (β = - 0.256, p < 0.001), smoking status (β = 0.156, p = 0.007) and age (β = 0.153, p = 0.008) were independent predictors of elevated CEA.

OSA was independently related to the elevated of serum CEA level, but not with presence of pulmonary nodule or ≥ 6 mm pulmonary nodule in LDCT. Further well-designed longitudinal studies with pathology available are needed to identify the association between OSA and risk of lung cancer.

Severe obesity is often present with non-alcoholic fatty liver disease (NAFLD) and obstructive sleep apnea (OSA). Emerging researches suggest OSA plays an important role in NAFLD development and progression while the relationship between OSA and NAFLD is still conflicting. The interaction of OSA and NAFLD should be further evaluated as obesity surges. The purpose of this study was to assess the prevalence of OSA and NAFLD in patients with obesity undergoing bariatric surgery and evaluate the association between OSA and severity of NAFLD.

141 patients with severe obesity undergoing preoperative polysomnography and intraoperative liver biopsy during bariatric surgery were investigated. Clinical, anthropometric variables, liver enzymes, fasting blood glucose, fasting serum insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) were measured. The severity of NAFLD was assessed by degree of steatosis, ballooning, intralobular inflammation, and NAFLD activity score. The diagnosis and severity assessment of OSA was based on an apnea/hypopnea index (AHI).

OSA was diagnosed in 127 (90.07%), NAFLD in 124 (87.94%), and non-alcoholic steatohepatitis in 72 (51.06%) patients. There was a statistical difference in BMI, waist circumstance, neck circumstance, high-density lipoprotein cholesterol, fasting insulin, and HOMA-IR among the three groups divided by the severity of AHI. In addition, the distribution of hepatic steatosis grades among the three groups was statistically different (p = 0.025). AHI was significantly associated with HOMA-IR and hepatic steatosis when assessing the association between OSA parameters and liver histology in NAFLD (p < 0.05). Patients with steatosis of grades 1-3 had significantly elevated aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, triglycerides, fasting insulin, fasting glucose, HOMA-IR, and AHI compared with the patients with steatosis of grade 0. In a multivariable logistic analysis, the positive association between AHI and hepatic steatosis attenuated after adjusting for HOMA-IR.

Prevalence of OSA and NAFLD was high in patients with obesity eligible for bariatric procedures. HOMA-IR, but not AHI, was an independent risk factor for hepatic steatosis in this population.

We aimed to identify the association between obstructive sleep apnea (OSA), insulin resistance (IR), and metabolic syndrome (MetS) in a nationwide population-based sample. A total of 7,900 adults with information on the STOP-Bang score and MetS (3,341 men and 4,469 women) were identified from the dataset of the Korea National Health and Nutrition Examination Survey 2019-2020. The association between OSA, IR, MetS, and its components was estimated using complex sample logistic regression analysis with adjustments for age, body mass index, residence, smoking status, alcohol consumption, household income, education, and the presence of diabetes. Participants with a high OSA score were more likely to have IR (odds ratio [OR] 2.78, 95% confidence interval [CI] 1.96-3.95 in men and OR 2.64, 95% CI 0.55-12.80 in women), MetS (OR 6.05, 95% CI 4.23-8.69 in men and OR 4.20, 95% CI 1.23-15.70 in women), and components of MetS, compared to individuals with a low OSA score. Compared to premenopausal women, postmenopausal women had a more intense association between OSA and IR (OR 1.78, 95% CI 0.13-24.43 for premenopausal women and OR 3.64, 95% CI 0.60-22.28 for postmenopausal women) and MetS (OR 2.58, 95% CI 0.23-29.55 for premenopausal women and OR 5.36, 95% CI 1.42-20.21 for postmenopausal women). OSA was associated with abdominal obesity and hypertension in premenopausal women, while all components of MetS were associated with OSA in postmenopausal women. Further studies are necessary to elucidate the underlying mechanisms of these findings.

As the detection of non-alcoholic fatty liver disease (NAFLD) is imperative for the prevention of its complications, we aimed to explore the predictive value of platelet to lymphocyte count ratio (PLR) and white blood cell count to mean platelet volume ratio (WBC/MPV) in relation to the occurrence of NAFLD among patients with obstructive sleep apnea-hypopnea syndrome (OSAHS).

This was a cross-sectional study consisting of 351 patients with OSAHS (279 with and 72 without NAFLD). The logistic regression analysis was performed to estimate associations between PLR, WBC/MPV, and NAFLD. Finally, the receiver operating characteristic curve (ROC curve) was used to analyze the efficacy of PLR and WBC/MPV in NAFLD prediction.

Compared to the OSAHS-only group, there was a rising trend in AHI and TS90% in the OSAHS + NAFLD group. And the logistic regression analysis identified average oxygen saturation (MaSO₂), WBC/MPV and PLR as predicted factors (odds ratio [OR] = 1.134, P = 0.031; OR = 7.559, P = 0.018, OR = 0.980, P < 0.001, respectively) for NAFLD in OSAHS patients. Moreover, compared with WBC/MPV, PLR, FLI, and APRI, a combination of WBC/MPV and PLR presented the largest AUC for the detection of NAFLD in BMI < 28 kg/m² (0.753, 95% CI 0.684-0.822), and in age ≥ 60 years subgroup (0.786, 95% CI 0.692-0.880) in ROC analysis. Meanwhile, a combination of WBC/MPV and PLR presented the second largest AUC for the detection of NAFLD in all subjects (0.743, 95% CI 0.708-0.831), as well as in the age < 60 years subgroup (0.729, 95% CI 0.652-0.806), only ranked after FLI, suggesting the combination of WBC/MPV and PLR has a good predictive value for NAFLD in OSAHS patients.

We confirmed that the levels of WBC/MPV, PLR, and MaSO₂ were closely related to the occurrence of NAFLD among OSAHS patients. Furthermore, our results highlighted the clinical combination of WBC/MPV and PLR levels could act as a simple and effective biomarker for screening NAFLD in patients with OSAHS.

Although obesity, asthma, and sleep-disordered breathing are interrelated, there is limited understanding of the independent contributions of body-mass index and pulmonary function on polysomnography in children with asthma.

We conducted a retrospective chart review on 448 7- to 18-year-old children with asthma who had undergone polysomnography testing between 1/2007-12/2011 to elucidate the association between spirometry variables, body-mass index, and polysomnography parameters, adjusting for asthma and antiallergic medications.

Obese children had poorer sleep architecture and more severe gas exchange abnormalities compared to healthy weight children. Multivariate analysis revealed an independent association of body-mass index with sleep efficiency, with more light and less deep sleep in both obese and healthy-weight children, and with baseline oxygen saturation and oxygen nadir in obese children. In obese children, forced vital capacity was independently associated with less deep sleep (time in N3 sleep) as well as with oxygen nadir, while among healthy-weight children, forced expiratory volume directly correlated but forced vital capacity inversely correlated with deep sleep. In obese children, inhaled corticosteroid was associated with baseline oxygen saturation, and montelukast was associated with lower end-tidal carbon dioxide. In healthy-weight children, inhaled corticosteroid was associated with arousal awakening index, and montelukast was associated with light sleep. Antiallergic medications were not independently associated with polysomnography parameters.

Pulmonary function, body-mass index, and asthma medications have independent and differing influences on sleep architecture and gas exchange polysomnography parameters in obese and healthy-weight children with asthma. Asthma medications are associated with improved gas exchange in obese children and improved sleep architecture in healthy-weight children with asthma.

Conrad LA, Nandalike K, Rani S, Rastogi D. Associations between sleep, obesity, and asthma in urban minority children. J Clin Sleep Med. 2022;18(10):2377-2385.

Non-alcoholic fatty liver disease (NAFLD) currently affects more than 25% of the world population and is rising. NAFLD can progress to non-alcoholic steatohepatitis that is associated with hepatic inflammation and fibrosis and can result in cirrhosis with subsequent liver failure. Non-alcoholic steatohepatitis (NASH) has now emerged as one of the leading etiologies for a liver transplant among adults in the United States. Given the rising incidence of liver transplants in patients with NASH-related cirrhosis, it is essential for anesthesiologists to be familiar with this condition as well as with NASH-related comorbidities and perioperative complications. Not only is NASH linked to metabolic syndrome, but it also is independently associated with cardiovascular disease, renal and thyroid dysfunction, obstructive sleep apnea (OSA), and a hypercoagulable state. The association with these conditions can affect the perioperative outcome of these patients, particularly because of increased mortality from major adverse cardiovascular events and sepsis. In order to decrease the perioperative morbidity and mortality of patients with NASH undergoing a liver transplant, a multidisciplinary approach to their perioperative management is essential, along with careful preoperative evaluation and aggressive intraoperative and postoperative monitoring. The focus of this review article is to provide a comprehensive overview of challenges associated with liver transplants in patients with NASH and to provide suggestions for appropriate patient selection and perioperative management.

Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease and refers to a wide spectrum of histological abnormalities ranging from simple steatosis (HE) to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis and hepatocellular carcinoma.

To assess the risk of obstructive sleep apnea syndrome (OSAS) and relating it to demographic, biochemical and histological data in patients with non-alcoholic fatty liver disease.

Cross-sectional cohort study in individuals with biopsy-proven NAFLD. Anthropometric and biochemical parameters, presence of metabolic syndrome and insulin resistance were evaluated. The Berlin Questionnaire (BQ) was applied to assess the risk of apnea and a food record was requested. Based on the BQ, participants were classified as high or low risk for OSAS. In the correlation of sleep apnea with the severity of NAFLD, presence of nonalcoholic steatohepatitis (NASH) and the degree of liver fibrosis were evaluated. Statistical analysis used the chi-square test, Student's t and bivariate logistic regression; values were expressed as mean ± standard deviation. This research project was approved by the Ethics Committee.

Regarding the parameters evaluated, significant differences were observed between the groups in terms of body mass index (BMI), waist and neck circumference. In the histological evaluation, patients classified as high risk were more likely to have fibrosis and NASH. In bivariate regression, the BMI, presence of fibrosis and steatohepatitis in the biopsy were independently associated with an elevated risk of the syndrome.

A high prevalence of risk for OSAS was observed in the studied group, with a higher risk being independently associated with BMI and presence of steatohepatitis, suggesting that it is a factor associated with the severity of the disease.

Obstructive sleep apnea (OSA) is characterized by upper airway collapse during sleep. Chronic intermittent hypoxia, sleep fragmentation, and inflammatory activation are the main pathophysiological mechanisms of OSA. OSA is highly prevalent in obese patients and may contribute to cardiometabolic risk by exerting detrimental effects on adipose tissue metabolism and potentiating the adipose tissue dysfunction typically found in obesity. This chapter will provide an update on: (a) the epidemiological studies linking obesity and OSA; (b) the studies exploring the effects of intermittent hypoxia and sleep fragmentation on the adipose tissue; (c) the effects of OSA treatment with continuous positive airway pressure (CPAP) on metabolic derangements; and (d) current research on new anti-diabetic drugs that could be useful in the treatment of obese OSA patients.

Understanding the pathomechanism of steatohepatitis (SH) is hampered by the difficulty of distinguishing between causes and consequences, by the broad spectrum of aetiologies that can produce the phenotype, and by the long time-span during which SH develops, often without clinical symptoms. We propose that SH develops in four phases with transitions: (i) priming lowers stress defence; (ii) triggering leads to acute damage; (iii) adaptation, possibly associated with cellular senescence, mitigates tissue damage, leads to the phenotype, and preserves liver function at a lower level; (iv) finally, senescence prevents neoplastic transformation but favours fibrosis (cirrhosis) and inflammation and further reduction in liver function. Escape from senescence eventually leads to hepatocellular carcinoma. This hypothesis for a pathomechanism of SH is supported by clinical and experimental observations. It allows organizing the various findings to uncover remaining gaps in our knowledge and, finally, to provide possible diagnostic and intervention strategies for each stage of SH development.

Expansion sphincter pharyngoplasty is a well-known palatal correction surgery applied for obstructive sleep apnea patients. Even though high success rates are reported, in some patients, the desired outcome cannot be achieved. Therefore, patient selection is crucial to avoid undesirable outcomes. In this study we present our results with expansion sphincter pharyngoplasty, and we aim to show the difference between supine and non-supine apnea in terms of their response to the surgery, in order to utilize position dependency for selection of surgical candidates.

Pre- and post-operative polysomnography results of patients who underwent expansion sphincter pharyngoplasty were analyzed retrospectively. Total AHI, supine AHI, non-supine AHI, supine/non-supine AHI ratio and surgical success values are compared.

85 patients were included to the study. Mean AHI significantly decreased from 48.7 ± 27.99 to 26.37 ± 21.16 with the surgery. Surgical success rate was found to be 51.8%. Both supine and non-supine apnea decreased significantly with the surgery, but the decrease was significantly higher in non-supine apnea (20.6% to 39.1% respectively, p = 0.016). There was significant negative correlation between pre-operative supine to non-supine AHI ratio and the change in AHI, showing that supine dominant patients had less improvement with the surgery (r = 0.274, p = 0.01).

Expansion sphincter pharyngoplasty is an effective surgery which achieves significant improvement in AHI. Non-supine respiratory events respond better to the surgery than supine events.

Obesity is now a worldwide epidemic ensuing an increase in comorbidities' prevalence, such as insulin resistance, type 2 diabetes (T2D), metabolic dysfunction-associated fatty liver disease (MAFLD), nonalcoholic steatohepatitis (NASH), hypertension, cardiovascular disease (CVD), autoimmune diseases, and some cancers, CVD being one of the main causes of death in the world. Several studies provide evidence for an association between MAFLD and atherosclerosis and cardio-metabolic disorders, including CVDs such as coronary heart disease and stroke. Therefore, the combination of MAFLD/NASH is associated with vascular risk and CVD progression, but the underlying mechanisms linking MAFLD/NASH and CVD are still under investigation. Several underlying mechanisms may probably be involved, including hepatic/systemic insulin resistance, atherogenic dyslipidemia, hypertension, as well as pro-atherogenic, pro-coagulant, and pro-inflammatory mediators released from the steatotic/inflamed liver. MAFLD is strongly associated with insulin resistance, which is involved in its pathogenesis and progression to NASH. Insulin resistance is a major cardiovascular risk factor in subjects without diabetes. However, T2D has been considered the most common link between MAFLD/NASH and CVD. This review summarizes the evidence linking obesity with MAFLD, NASH, and CVD, considering the pathophysiological molecular mechanisms involved in these diseases. We also discuss the association of MAFLD and NASH with the development and progression of CVD, including structural and functional cardiac alterations, and pharmacological strategies to treat MAFLD/NASH and cardiovascular prevention.

Non-alcoholic fatty liver disease (NAFLD) and its more severe form non-alcoholic steatohepatitis (NASH) are a major public health concern with high and increasing global prevalence, and a significant disease burden owing to its progression to more severe forms of liver disease and the associated risk of cardiovascular disease. Treatment options, however, remain scarce, and a better understanding of the pathological and physiological processes involved could enable the development of new therapeutic strategies. One process implicated in the pathology of NAFLD and NASH is cellular oxygen sensing, coordinated largely by the hypoxia-inducible factor (HIF) family of transcription factors. Activation of HIFs has been demonstrated in patients and mouse models of NAFLD and NASH and studies of activation and inhibition of HIFs using pharmacological and genetic tools point toward important roles for these transcription factors in modulating central aspects of the disease. HIFs appear to act in several cell types in the liver to worsen steatosis, inflammation, and fibrosis, but may nevertheless improve insulin sensitivity. Moreover, in liver and other tissues, HIF activation alters mitochondrial respiratory function and metabolism, having an impact on energetic and redox homeostasis. This article aims to provide an overview of current understanding of the roles of HIFs in NAFLD, highlighting areas where further research is needed.

Mechanisms involving obstructive sleep apnea (OSA) and nonalcoholic fatty liver disease (NAFLD) are under increasing assessment. This study evaluated the correlation of OSA with the severity of NAFLD.

Prospective study in which patients with at least one of metabolic syndrome (MS) criteria were initially assessed by the NAFLD fibrosis score and according to the outcome (intermediate or high risk of advanced fibrosis) underwent liver biopsy (exception of patients with clinical, ultrasound or endoscopic diagnosis of cirrhosis). All patients performed polysomnography. For statistical analysis, the patients were assembled into two groups: (1) without apnea or mild apnea and (2) moderate or severe apnea. In the correlation of OSA with the severity of NAFLD, the risk factors evaluated were: degree of steatosis, presence and severity of nonalcoholic steatohepatitis (NASH) and fibrosis.

Fifty-one patients were evaluated, 80.4% had systemic arterial hypertension (SAH), 68.6% type 2 diabetes mellitus, 62.7% dyslipidemia and 96.1% MS. Regarding the histological evaluation (n = 48), all had steatosis, 95.8% steatohepatitis and 83.3% fibrosis. In polysomnography, 80.4% were group 1 and 19.6% group 2. In univariate analysis, no correlation was found between steatosis severity, NASH and presence or severity of fibrosis with OSA. A multivariate analysis adjusted for obesity level, found that patients with moderate to severe OSA had an increased risk of hepatic fibrosis (odds ratio 1.22, 95% confidence interval: 1.02-1.45, P = 0.027).

The present study demonstrated an association between fibrosis and moderate to severe OSA, regardless of obesity.

The growing number of patients with obstructive sleep apnea is challenging healthcare systems worldwide. Obstructive sleep apnea is characterized by chronic intermittent hypoxaemia, episodes of apnea and hypopnea, and fragmented sleep. Cardiovascular and metabolic diseases are common in obstructive sleep apnea, also in lean patients. Further, comorbidity burden is not unambiguously linked to the severity of obstructive sleep apnea. There is a growing body of evidence revealing diverse functions beyond the conventional tasks of different organs such as carotid body and gut microbiota. Chronic intermittent hypoxia and sleep loss due to sleep fragmentation are associated with insulin resistance. Indeed, carotid body is a multi-sensor organ not sensoring only hypoxia and hypercapnia but also acting as a metabolic sensor. The emerging evidence shows that obstructive sleep apnea and particularly chronic intermittent hypoxia is associated with non-alcoholic fatty liver disease. Gut dysbiosis seems to be an important factor in the pathophysiology of obstructive sleep apnea and its consequences. The impact of sleep fragmentation and intermittent hypoxia on the development of metabolic syndrome may be mediated via altered gut microbiota. Circadian misalignment seems to have an impact on the cardiometabolic risk in obstructive sleep apnea. Dysfunction of cerebral metabolism is also related to hypoxia and sleep fragmentation. Therefore, obstructive sleep apnea may alter cerebral metabolism and predispose to neurocognitive impairment. Moreover, recent data show that obstructive sleep apnea independently predicts impaired lipid levels. This mini-review will provide novel insights into the mechanisms of metabolic dysfunction in obstructive sleep apnea combining recent evidence from basic, translational and clinical research, and discuss the impact of positive airway pressure treatment on metabolic disorders.

Rationale: Obstructive sleep apnea (OSA) is associated with development of nonalcoholic fatty liver disease (NAFLD). The effects of continuous positive airway pressure (CPAP) on NAFLD in patients with concomitant OSA are unknown.Objectives: To investigate the effects of autoadjusting CPAP versus subtherapeutic CPAP treatment over 6 months on NAFLD activities.Methods: Patients with NAFLD and OSA, as defined by respiratory event index ≥5/h diagnosed by a validated level 3 Embletta device, were randomized into group A) autoadjusting CPAP (4-20 cm H₂O) or group B) subtherapeutic CPAP (pressure fixed at 4 cm H₂O). The primary endpoint was the difference in changes in intrahepatic triglyceride as measured by proton magnetic resonance spectroscopy after 6 months of therapy. Key secondary endpoints included changes in controlled attenuation parameter (CAP) and liver stiffness measurement measured with transient elastography, and serum cytokeratin-18 fragment.Measurements and Main Results: A total of 120 patients were randomized equally into two groups. There were significant correlations between CAP and respiratory event index (r = 0.203, P = 0.026), percentage of total recording time with Sa_O2 < 90% (r = 0.265, P = 0.003), and oxygen desaturation index (r = 0.214, P = 0.019). After 6 months of treatment, there were no significant differences of changes in primary and secondary endpoints between the two treatment groups. Regression analysis showed that weight change over 6 months correlated with changes in both intrahepatic triglyceride and CAP (P < 0.001).Conclusions: Despite significant correlations between hepatic steatosis and markers of severity of OSA, CPAP alone did not improve hepatic steatosis and fibrosis. However, the additional role of weight reduction through lifestyle modification deserves further investigation.

Obstructive Sleep Apnea (OSA) is closely associated with obesity. Weight loss ameliorates OSA and its associated metabolic disorders. A high protein intake may improve weight loss through increased energy expenditure, and fat-free mass maintenance during weight loss.

To evaluate the effects of a low-energy, high-protein diet on OSA severity and metabolic parameters in obese men.

Forty-five OSA obese (BMI ≥ 30 kg/m²) males were included in this randomized study and submitted to nocturnal polysomnography, body composition measured by plethysmography, biochemical analyses of blood glucose, insulin and lipids, and food intake evaluations before and after one month of a low-energy diet. Diets were designed to create a 30% deficit in total energy expenditure with 1.6 g of protein/kg/day (High Protein group - HP) or 0.8 g of protein/kg/day (Low Protein group - LP).

Only a time effect of the intervention was observed in body mass (-3.7 ± 2.0% for the LP group and -4.0 ± 1.5% for the HP group; p < 0.001), Body Mass Index (p < 0.001), fat mass in kg (p < 0.01) and fat-free mass in kg (p < 0.01). Significant improvements in Apnea Hypopnea Index were observed in both groups (54.0 ± 25.0 to 33.7 ± 31.7 in LP group; 39.7 ± 24.3 to 21.4 ± 25.9 in HP group; p = 0.06). Improvements of 38% and 46% in the Apnea-Hypopnea Index were observed in the LP and HP groups, respectively. Both interventions provided equivalent metabolic benefits as reductions in glucose (p < 0.001), insulin (p < 0.001), HOMA-IR (p = 0.005), triglycerides (p = 0.002), and in total cholesterol (p = 0.004).

One month of a low-energy diet resulted in significant improvements in OSA severity in obese men. Increased protein intake during a short period of low-energy diet had no further beneficial effects on OSA severity or biochemical parameters than a standard protein diet. Registered under ClinicalTrials.gov Identifier no. NCT01985035.

Sleep disturbance is a common feature of chronic liver disease (CLD) with impact on health-related quality of life; 60-80% of patients with CLD report subjective poor sleep; frequent presentations of sleep disturbance include insomnia, reduced sleep efficiency, increased sleep latency, reduced time in rapid eye movement (REM) sleep, restless leg syndrome and excessive daytime sleepiness (EDS). Key contributors to sleep disturbance include hepatic encephalopathy (HE) and circadian rhythm imbalance due to altered melatonin metabolism. Specific conditions causing CLD, such as non-alcoholic fatty liver disease (NAFLD), chronic viral hepatitis and primary biliary cholangitis (PBC) result in different types of sleep disturbance, and the treatment of these conditions can often also lead to sleep disturbance. There are currently limited management options for sleep disturbance in CLD. Obstructive sleep apnoea (OSA) is a common condition that causes chronic intermittent hypoxia due to airway collapse during sleep. This chronic intermittent hypoxia appears to contribute to the development of NAFLD. The presence of reactive oxygen species and the overexpression of hypoxia inducible factor 1-alpha secondary to hypoxia may be responsible for the second 'hit' of the 'two-hit' hypothesis of NAFLD. Treatment of the intermittent hypoxia with continuous positive airway pressure therapy has limited efficacy against liver dysfunction. There remain many outstanding areas of investigation in the management of sleep disturbance in CLD, and of liver dysfunction in OSA.

Obstructive sleep apnea (OSA) is associated with obesity and risk for type 2 diabetes. In this community-based study, we thoroughly investigated fatty acid metabolism, incretin response, glucose tolerance, insulin secretion and insulin sensitivity, and autonomic nerve activity in men with or without OSA.

Fifteen men without diabetes but with signs of severe OSA, defined as apnea-hypopnea index (AHI) >30, and 15 age- and BMI-matched men without OSA (AHI < 5) were recruited from a community-based cohort. Assessments included clinical and anthropometric measurements, a 2-h oral glucose tolerance test (OGTT), and autonomic nerve activity using heart rate variability (HRV).

Men with OSA had higher body fat % than BMI-matched men without OSA (p = 0.046) and it was associated with markers of insulin resistance. The area under the curve for nonesterified fatty acids (NEFA) during OGTT was higher in men with OSA (p = 0.021) and fasting NEFA levels were numerically higher (p = 0.097). The plasma glucose at fasting and during OGTT was higher in men with OSA (p < 0.001). Incretin response was similar between groups. Fasting and OGTT-derived indices indicated impaired insulin sensitivity in men with OSA. Compared with men without OSA, Matsuda index (p = 0.068) and Gutt index (p < 0.01) were lower in men with OSA. The HRV measures did not differ between groups.

Our study suggests that fatty acid handling, glucose tolerance, and insulin sensitivity are impaired in men with severe OSA. This might partly be explained by the increased body fat percentage.

In January 2019, a European Respiratory Society research seminar entitled "Targeting the detrimental effects of sleep disturbances and disorders" was held in Dublin, Ireland. It provided the opportunity to critically review the current evidence of pathophysiological responses of sleep disturbances, such as sleep deprivation, sleep fragmentation or circadian misalignment and of abnormalities in physiological gases such as oxygen and carbon dioxide, which occur frequently in respiratory conditions during sleep. A specific emphasis of the seminar was placed on the evaluation of the current state of knowledge of the pathophysiology of cardiovascular and metabolic diseases in obstructive sleep apnoea (OSA). Identification of the detailed mechanisms of these processes is of major importance to the field and this seminar offered an ideal platform to exchange knowledge, and to discuss pitfalls of current models and the design of future collaborative studies. In addition, we debated the limitations of current treatment strategies for cardiometabolic complications in OSA and discussed potentially valuable alternative approaches.

Oxygen is both vital and toxic to life. Molecular oxygen is the most used substrate in the human body and is required for several hundred diverse biochemical reactions. The discovery of the PHD-HIF-pVHL system revolutionized our fundamental understanding of oxygen sensing and cellular adaptations to hypoxia. It deepened our knowledge of the biochemical underpinnings of numerous diseases, ranging from anemia to cancer. Cellular dysfunction and tissue pathology can result from a mismatch of oxygen supply and demand. Recent work has shown that mitochondrial disease models display tissue hyperoxia and that disease pathology can be reversed by normalization of excess oxygen, suggesting that certain disease states can potentially be treated by modulating oxygen levels. In this review, we describe cellular and organismal mechanisms of oxygen sensing and adaptation. We provide a revitalized framework for understanding pathologies of too little or too much oxygen.

Lipid metabolism deregulation constitutes the pathogenic basis for the development of atherosclerosis and justifies a high incidence of cardiovascular-related morbidity and mortality. Some data suggest that dyslipidemia may be associated with sleep-disordered breathing, mainly obstructive sleep apnea (OSA), due to alterations in fundamental biochemical processes, such as intermittent hypoxia (IH). The aim of this systematic review was to identify and critically evaluate the current evidence supporting the existence of a possible relationship between OSA and alterations in lipid metabolism. Much evidence shows that, during the fasting state, OSA and IH increase lipid delivery from the adipose tissue to the liver through an up-regulation of the sterol regulatory element-binding protein-1 and stearoyl-CoA desaturase-1, increasing the synthesis of cholesterol esters and triglycerides. In the postprandial state, lipoprotein clearance is delayed due to lower lipoprotein lipase activity, probably secondary to IH-up-regulation of angiopoietin-like protein 4 and decreased activity of the peroxisome proliferator-activated receptor alpha. Moreover, oxidative stress can generate dysfunctional oxidized lipids and reduce the capacity of high-density lipoproteins (HDL) to prevent low-density lipoprotein (LDL) oxidation. In the clinical field, several observational studies and a meta-regression analysis support the existence of a link between OSA and dyslipidemia. Although there is evidence of improved lipid profile after apnea-hypopnea suppression with continuous positive airway pressure (CPAP), the majority of the data come from observational studies. In contrast, randomized controlled trials evaluating the effects of CPAP on lipid metabolism present inconclusive results and two meta-analyses provide contradictory evidence.

Obstructive sleep apnea (OSA) and nonalcoholic fatty liver disease (NAFLD) are common in subjects with severe obesity. It has been suggested that insulin resistance and systemic inflammation may play a role in the development of nonalcoholic steatohepatitis (NASH), but the mechanisms remain controversial. The aim of this study was to explore the influence of OSA on liver injury and its potential mechanisms in severely obese patients with NAFLD.

Severely obese patients requiring bariatric surgery were consecutively recruited between November 2017 and June 2018. Demographic, biochemical, liver ultrasound, and ambulatory polygraph data were collected.

One hundred fifty-three subjects with liver ultrasound-verified NAFLD were classified into three groups according to the apnea-hypopnea index (AHI). The level of serum alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (GGT) tended to increase with more severe OSA (P = 0.024 and P = 0.004, respectively). In the unadjusted analysis, both ALT and GGT were positively correlated with AHI, oxygen desaturation index, percentage of total sleep time spent with oxyhemoglobin saturation below 90%, male sex, homeostasis model assessment of insulin resistance (HOMA-IR), and total cholesterol, while liver enzymes were negatively related to lowest oxygen saturation. In multiple regression analysis, AHI (odds ratio (OR) = 1.052, P = 0.044) and HOMA-IR (OR = 1.135, P = 0.001) were independent risk factors for an elevated ALT level. High-sensitivity C-reactive protein (hs-CRP) was positively associated with BMI and GGT (r = 0.349 and r = 0.164 (P < 0.05), respectively), and no correlation was found between hs-CRP and AHI or other parameters of hypoxia. hs-CRP and GGT remained significantly correlated after adjusting for confounding parameters (OR = 2.509, P = 0.013).

OSA may play a role in liver injury among severely obese individuals with NAFLD. Insulin resistance and systemic inflammation were possible contributing factors in this process.

Recent studies have demonstrated that obstructive sleep apnea (OSA) is associated with the development and evolution of nonalcoholic fatty liver disease (NAFLD), independent of obesity or other shared risk factors. Like OSA, NAFLD is a prevalent disorder associated with major adverse health outcomes: Patients with NAFLD may develop cirrhosis, liver failure, and hepatocellular carcinoma. One major finding that has emerged from these studies is that the OSA-NAFLD association is related to the degree of nocturnal hypoxemia in OSA. Animal models have therefore largely focused on intermittent hypoxia, a key manifestation of OSA, to shed light on the mechanisms by which OSA may give rise to the complex metabolic disturbances that are seen in NAFLD. Intermittent hypoxia leads to tissue hypoxia and can result in oxidative stress, mitochondrial dysfunction, inflammation, and overactivation of the sympathetic nervous system, among many other maladaptive effects. In such models, intermittent hypoxia has been shown to cause insulin resistance, dysfunction of key steps in hepatic lipid metabolism, atherosclerosis, and hepatic steatosis and fibrosis, each of which is pertinent to the development and/or progression of NAFLD. However, many intriguing questions remain unanswered: Principally, how aggressively should the clinician screen for NAFLD in patients with OSA, and vice versa? In this review, we attempt to apply the best evidence from animal and human studies to highlight the relationship between these two disorders and to advocate for further trials aimed at defining these relationships more precisely.

This study was to investigate the degree of susceptibility to intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), between the two mice inbred lines C57BL/6N (6N) and C57BL/6J (6J).

Four-week old male mice of 6N and 6J substrains (n = 8) were randomized to standard diet (SD) group or high fat (HF) diet group. At the age of 13-week, all two groups of mice were subjected to either air or IH (IH30; thirty hypoxic events per hour) for one week.

All mice fed with HF diet exhibited obesity with more body weight and fat mass (percentage to body weight) gain. IH reduced serum LDL, HDL and total cholesterol levels in lean 6J mice. In obese mice, IH lowered obesity-induced serum total cholesterol level in 6J substrain but raised further in 6N substrain. Furthermore, IH caused elevation of serum FFA and MDA levels, and pro-inflammatory cytokines MCP-1 and IL-6 levels in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) of lean 6J but not lean 6N mice. There was reduced number of adipocytes and elevation of macrophages in SAT and VAT of HF-induced obese mice of both substrains. IH led to increased number of adipocytes and macrophages in SAT of lean 6J mice.

The genetic difference between 6N and 6J mice may have direct impact on metabolic and inflammatory responses after IH. Therefore, attention must be given for the selection of C57BL mice substrains in the experimental IH-exposed mouse model.

The incidence of nonalcoholic fatty liver disease (NAFLD) is continuing to rise worldwide, and it is estimated that this disquieting trend will continue for another 10-15 years before prevalence begins to decrease. NAFLD is the hepatic manifestation of metabolic syndrome. As obesity, diabetes, and other lifestyle-related diseases continue to rise, the spectrum of NAFLD, e.g., nonalcoholic steatohepatitis, liver fibrosis, liver cirrhosis, liver-related morbidity, and mortality, will increase in parallel. Its widespread prevalence and associated economic burden have drawn significant attention, and a multitude of pharmaceutical companies are participating in active research trying to find a "cure". Unfortunately, as of now, no targeted treatment exists to treat this condition, and therefore, emphasis has been on its prevention. The current review focuses on the epidemiology, clinical characteristics, risk factors, and clinical outcomes of NAFLD in Western countries. It is important to understand the magnitude of NAFLD and its risk factors in Western countries where the prevalence of NAFLD has now reached epidemic proportions to identify the best strategy to prevent and possibly control this epidemic.

Nonalcoholic fatty liver disease (NAFLD), a disorder of altered metabolic pathways, is increasing worldwide. Recent studies established obstructive sleep apnea (OSA) and chronic intermittent hypoxia (CIH) as NAFLD risk factors. Studies have ascertained that CIH is independently related to NAFLD. Continuous positive airway pressure (CPAP) shows inconsistent results regarding its efficacy in improving NAFLD. Observational, longer duration CPAP therapy studies have shown positive outcomes, whereas shorter duration, randomized controlled trials have shown no benefit. A multifaceted approach to NAFLD management with sufficiently longer duration of CPAP therapy may be beneficial in patients with moderate to severe OSA.