Obstructive sleep apnoea is characterized by chronic intermittent hypoxaemia and is independently associated with an increased risk of metabolic comorbidities (e.g. type II diabetes and ischaemic heart disease). These comorbidities could be attributable to hypoxaemia‐induced alterations in blood lipid profiles. However, it remains unclear whether intermittent hypoxaemia alters triglyceridaemia differently between biological sexes. Therefore, we used a randomized crossover design to examine whether 6 h of moderate intermittent hypoxaemia (15 hypoxaemic cycles/h, 85% oxyhaemoglobin saturation) alters plasma triglyceride levels differently between men and women after a high‐fat meal. Relative to men, women displayed lower levels of total triglycerides, in addition to denser triglyceride‐rich lipoprotein triglycerides (TRL‐TG; mainly very low‐density lipoprotein triglycerides and chylomicron remnant triglycerides) and buoyant TRL‐TG (mainly chylomicron triglycerides) during normoxia (ambient air) and intermittent hypoxaemia (sex × time: all P ≤ 0.008). Intermittent hypoxaemia led to higher triglyceride levels (condition: all P ≤ 0.016); however, this effect was observed only in men (sex × condition: all P ≤ 0.002). Compared with normoxia, glucose levels were higher in men and lower in women during intermittent hypoxaemia (sex × condition: P < 0.001). The different postprandial responses between biological sexes occurred despite similar reductions in mean oxyhaemoglobin saturation and similar elevations in insulin levels, non‐esterified fatty acid levels and mean heart rate (sex × condition: all P ≥ 0.185). These results support growing evidence showing that intermittent hypoxaemia impacts men and women differently, and they might help to explain biological sex‐related discrepancies in the rate of certain comorbidities associated with intermittent hypoxaemia. image Key points: Intermittent hypoxaemia is a key characteristic of obstructive sleep apnoea and alters lipid metabolism in multiple tissues, resulting in increased circulating triglyceride levels, an important risk factor for cardiometabolic diseases. Circulating triglyceride levels are regulated differently between biological sexes, with women typically displaying much lower fasting and postprandial triglyceride levels than men, partly explaining why women of all ages experience lower mortality rates from cardiometabolic diseases. In this study, healthy young men and women consumed a high‐fat meal and were then exposed to 6 h of intermittent hypoxaemia or ambient air. We show that postprandial triglyceride levels are significantly lower in women compared with men and that intermittent hypoxaemia leads to higher postprandial triglyceride levels in men only. These results might help us to understand better why women living with obstructive sleep apnoea experience lower rates of cardiometabolic diseases (e.g. type II diabetes and ischaemic heart disease) than men living with obstructive sleep apnoea.

Under insulin-stimulated conditions, skeletal muscle is the largest glucose consumer in the body. Mitochondrial dysfunction and damage to this tissue from oxidative stress are linked to the pathogenesis of type 2 diabetes. Environmental exposure to dichlorodiphenyltrichloroethane (DDT) and its metabolite, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), has been associated with the incidence of type 2 diabetes as well as altered oxidative stress and mitochondrial dysfunction in non-muscle tissues. We hypothesized that energy metabolism and insulin sensitivity in skeletal muscle will be altered with exposure to DDT and DDE. In this pilot study, mitochondrial function was measured in permeabilized muscle fibers from Sprague-Dawley rats after one week of exposure to a single injection of DDT (40 μg/kg), a dose comparable to DDT levels in the diets of the Inuit of Northern Canada. The levels of oxidative phosphorylation chain complexes and ROS detoxification enzymes were measured in muscle tissue from these specimens. This acute in vivo exposure to DDT decreased muscle mitochondrial function by 45% without affecting the levels of mitochondrial oxidative phosphorylation chain complexes nor levels of ROS detoxification enzymes. To isolate the effects of DDT and DDE exposure on muscle, L6 myotubes were exposed to DDT or DDE (0, 10, 100, 1000, 10 000 nM) for 24 h. Only very high concentrations of DDT and DDE (1 000 – 10 000 nM) altered maximal respiration with only DDT altering basal glucose uptake in L6 myotubes. This did not alter levels of ROS detoxification enzymes or malondialdehyde (MDA) in L6 myotubes. Altogether, acute exposure to environmentally relevant doses of DDT resulted in muscle mitochondrial dysfunction in vivo in rats, but not when muscle cells were directly exposed to the pollutant or its metabolite.

It is increasingly recognized that hypoxia may develop in adipose tissue as its mass expands. Adipose tissue is also the main reservoir of lipophilic pollutants, including polychlorinated biphenyls (PCBs). Both hypoxia and PCBs have been shown to alter adipose tissue functions. The signaling pathways induced by hypoxia and pollutants may crosstalk, as they share a common transcription factor: aryl hydrocarbon receptor nuclear translocator (ARNT). Whether hypoxia and PCBs crosstalk and affect adipokine secretion in human adipocytes remains to be explored. Using primary human adipocytes acutely co-exposed to different levels of hypoxia (24 h) and PCB126 (48 h), we observed that hypoxia significantly inhibits the PCB126 induction of cytochrome P450 (CYP1A1) transcription in a dose-response manner, and that Acriflavine (ACF)—an HIF1α inhibitor—partially restores the PCB126 induction of CYP1A1 under hypoxia. On the other hand, exposure to PCB126 did not affect the transcription of the vascular endothelial growth factor-A (VEGFA) under hypoxia. Exposure to hypoxia increased leptin and interleukin-6 (IL-6), and decreased adiponectin levels dose-dependently, while PCB126 increased IL-6 and IL-8 secretion in a dose-dependent manner. Co-exposure to PCB126 and hypoxia did not alter the adipokine secretion pattern observed under hypoxia and PCB126 exposure alone. In conclusion, our results indicate that (1) hypoxia inhibits PCB126-induced CYP1A1 expression at least partly through ARNT-dependent means, suggesting that hypoxia could affect PCB metabolism and toxicity in adipose tissue, and (2) hypoxia and PCB126 affect leptin, adiponectin, IL-6 and IL-8 secretion differently, with no apparent crosstalk between the two factors.

Persistent organic pollutants (POPs) accumulation and hypoxia are two factors proposed to adversely alter adipose tissue (AT) functions in the context of excess adiposity. Studies have shown that preadipocytes exposure to dioxin and dioxin-like POPs have the greatest deleterious impact on rodent and immortalized human preadipocyte differentiation, but evidence on human preadipocytes is lacking. Additionally, hypoxia is known to strongly interfere with the dioxin-response pathway. Therefore, we tested the effects of pre-differentiation polychlorinated biphenyl (PCB)126 exposure at 10 µM for 3 days and subsequent differentiation under hypoxia on human subcutaneous adipocytes (hSA) differentiation, glucose uptake and expression of selected metabolism- and inflammation-related genes. Pre-differentiation PCB126 exposure lowered the adenosine triphosphate (ATP) content, glucose uptake and leptin expression of mature adipocytes but had limited effects on differentiation under normoxia (21% O₂). Under hypoxia (3% O₂), preadipocytes ability to differentiate was significantly reduced as reflected by significant decreased lipid accumulation and downregulation of key adipocyte genes such as peroxisome proliferator-activated receptor gamma (PPARγ) and adiponectin. Hypoxia increased glucose uptake and glucose transporter 1 (GLUT1) expression but abolished the adipocytes insulin response and GLUT4 expression. The expression of pro-inflammatory adipokine interleukin-6 (IL-6) was slightly increased by both PCB126 and hypoxia, while IL-8 expression was significantly increased only following the PCB126-hypoxia sequence. These observations suggest that PCB126 does not affect human preadipocyte differentiation, but does affect the subsequent adipocytes population, as reflected by lower ATP levels and absolute glucose uptake. On the other hand, PCB126 and hypoxia exert additive effects on AT inflammation, an important player in the development of chronic diseases such as type 2 diabetes and cardiovascular diseases.

Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxemia, which is associated with progressive loss of kidney function, where postprandial fluctuations in renal physiology may further compromise oxygen supply and kidney function. Therefore, we measured biomarkers of acute kidney injury (AKI) following a high‐fat meal with and without intermittent hypoxemia. Eighteen healthy young men (mean age [SD]: 22.7 years [3.1]) and seven middle‐aged to older individuals with OSA (54.4 years [6.4]) consumed a high‐fat meal during normoxia or intermittent hypoxemia (~15 hypoxic cycles per hour, ~85% oxyhemoglobin saturation) for 6 h. We observed no changes in estimated glomerular filtration rate and plasma concentrations of creatinine, neutrophil gelatinase‐associated lipocalin (NGAL), and kidney injury molecule‐1 (KIM‐1) at any measured time points. In both groups, plasma concentrations of interleukin‐18 (IL‐18) increased after 6 h during normoxia only (p = 0.033, η_p² = 0.122), and plasma concentrations of liver‐type fatty acid‐binding protein (L‐FABP) transiently decreased after 3 h in both conditions (p = 0.008, η_p² = 0.152). These findings indicate that AKI biomarkers are not acutely elevated during the postprandial state with or without intermittent hypoxemia, suggesting that other mechanisms may play more important roles in the progression of kidney disease in OSA.

Hypoxemia occurs during exposure to high altitude (continuous hypoxemia) or in the context of breathing disorders such as obstructive sleep apnea (OSA; intermittent hypoxemia). Growing evidence demonstrates that hypoxemia induces an anorexigenic effect on appetite; however, few studies have assessed hypoxemia-related reductions in appetite during acute passive exposures and during intermittent hypoxemia. This study thus pooled together four same-single-site randomized crossover trials using simulated models of high altitude (fraction of inspired oxygen = 0.1200, similar to 5000 m) and moderate OSA (similar to 15 hypoxemic cycles per hour, similar to 85 oxyhemoglobin saturation). Changes in appetite were evaluated during 6 h of passive normoxia and intermittent or continuous hypoxemia in postprandial or fasting states among healthy young adults (n = 40) and middle-aged individuals living with OSA (n = 7). Our results demonstrate that (1) acute passive intermittent hypoxemia leads to statistically significant, but likely not clinically significant reductions in appetite in the postprandial state, (2) the anorexigenic effect of acute passive hypoxemia on appetite is not consistent across hypoxemic methods and nutritional states, and (3) variations in individual factors may influence appetite responses during normoxia and hypoxemia. These findings indicate that the effect of acute passive hypoxemia on appetite is heterogeneous, particularly across different hypoxemic methods and nutritional states.