间歇性低氧对肥胖小鼠瘦素及其受体表达的影响

为探讨适度低氧环境对体重的影响及其作用机制,明确瘦素在其中的作用,用高脂饮食建立小鼠肥胖模型并观察间歇性低氧的干预效果。健康昆明小鼠随机分为4组（每组20只）,正常对照组：喂正常食物,不进行间歇性低氧训练;低氧组：喂正常食物,并进行间歇性低氧训练;肥胖组：喂高脂、高糖食物,但不进行间歇性低氧训练;低氧＋肥胖组,喂高脂、高糖食物,并进行间歇性低氧训练。40d后,测量小鼠体重,用酶联免疫吸附法测定血清瘦素水平,免疫组织化学检测肝脏瘦素受体表达,苏丹Ⅲ染色检测肝脏脂肪细胞分布和密度。结果显示,与正常对照组相比,肥胖组小鼠平均体重和平均血清瘦素水平显著升高,肝脏分布大量脂肪细胞,提示高脂模型建立成功;经过间歇性低氧训练后,低氧组和低氧＋肥胖组小鼠的平均体重及肝脏脂肪细胞分布密度和范围分别较对照组和肥胖组低,而血清瘦素水平明显增高;低氧＋肥胖组小鼠肝脏瘦素受体的表达高于肥胖组。结果提示,适度的间歇性低氧可以通过提高血清瘦素水平和增强肝脏瘦素受体表达而使体重减轻,并有效防止肝细胞脂肪变。     

Effect of Intermittent Cold Exposure on Brown Fat Activation,Obesity, and Energy Homeostasis in Mice

Homeotherms have specific mechanisms to maintain a constant core body temperature despite changes in thermal environment, food supply, and metabolic demand. Brown adipose tissue, the principal thermogenic organ, quickly and efficiently increases heat production by dissipating the mitochondrial proton motive force. It has been suggested that activation of brown fat, via either environmental (i.e. cold exposure) or pharmacologic means, could be used to increase metabolic rate and thus reduce body weight. Here we assess the effects of intermittent cold exposure (4°C for one to eight hours three times a week) on C57BL/6J mice fed a high fat diet. Cold exposure increased metabolic rate approximately two-fold during the challenge and activated brown fat. In response, food intake increased to compensate fully for the increased energy expenditure; thus, the mice showed no reduction in body weight or adiposity. Despite the unchanged adiposity, the cold-treated mice showed transient improvements in glucose homeostasis. Administration of the cannabinoid receptor-1 inverse agonist AM251 caused weight loss and improvements in glucose homeostasis, but showed no further improvements when combined with cold exposure. These data suggest that intermittent cold exposure causes transient, meaningful improvements in glucose homeostasis, but without synergy when combined with AM251. Since energy expenditure is significantly increased during cold exposure, a drug that dissociates food intake from metabolic demand during cold exposure may achieve weight loss and further metabolic improvements.     

Estrogen improved metabolic syndrome through down-regulation of VEGF and HIF-1α to inhibit hypoxia of periaortic and intra-abdominal fat in ovariectomized female rats

Metabolic syndrome (MBS), a cluster of metabolic abnormalities and visceral fat accumulation, increases cardiovascular risks in postmenopausal women. In addition to visceral fat, perivascular adipose tissue has been recently found to play an important role in vascular pathophysiology. Hence, the present study investigates the effects of estrogen on both intra-abdominal fat (visceral fat) and periaortic fat (perivascular fat) accumulation as well as hypoxia in ovariectomized female rats. Female rats were divided into sham operation, ovariectomy and ovariectomy with 17β-estradiol supplementation groups. Twelve weeks later, we found that estrogen improved MBS via reducing body weight gain, the weight of periaortic and intra-abdominal fat, hepatic triglyceride, and total serum cholesterol levels. Estrogen also increased insulin sensitivity through restoring glucose and serum leptin levels. For periaortic fat, western blot showed estrogen inhibited hypoxia by reducing the levels of VEGF and HIF-1α, which is consistent with the results from immunohistochemical staining. The correlation analysis indicated that perivascular fat had a positive correlation with body weight, intra-abdominal fat or serum total cholesterol, but a negative correlation with insulin sensitivity index. For intra-abdominal fat, real-time fluorescent RT-PCR showed estrogen improved fat dysfunction via reducing the levels of relative leptin, MCP-1 but increasing adiponectin mRNA. Estrogen reduced the levels of VEGF and HIF-1α to inhibit hypoxia but restored the levels of PPARγ and Srebp-1c, which are important for lipid capacity function of intra-abdominal fat. These results demonstrated estrogen improved MBS through down-regulating VEGF and HIF-1α to inhibit hypoxia of periaortic and intra-abdominal fat in ovariectomized female rats.     

Efficacy and safety of dietary supplements containing CLA for the treatment of obesity: evidence from animal and human studies

Dietary supplements containing conjugated linoleic acid (CLA) are widely promoted as weight loss agents available over the counter and via the Internet. In this review, we evaluate the efficacy and safety of CLA supplementation based on peer-reviewed published results from randomized, placebo-controlled, human intervention trials lasting more than 4 weeks. We also review findings from experimental studies in animals and studies performed in vitro. CLA appears to produce loss of fat mass and increase of lean tissue mass in rodents, but the results from 13 randomized, controlled, short-term (<6 months) trials in humans find little evidence to support that CLA reduces body weight or promotes repartitioning of body fat and fat-free mass in man. However, there is increasing evidence from mice and human studies that the CLA isomer trans-10, cis-12 may produce liver hypertrophy and insulin resistance via a redistribution of fat deposition that resembles lipodystrophy. CLA also decreases the fat content of both human and bovine milk. In conclusion, although CLA appears to attenuate increases in body weight and body fat in several animal models, CLA isomers sold as dietary supplements are not effective as weight loss agents in humans and may actually have adverse effects on human health.     

Role of nitric oxide in cardiovascular adaptation to intermittent hypoxia

Hypoxia is one of the most frequently encountered stresses in health and disease. The duration, frequency, and severity of hypoxic episodes are critical factors determining whether hypoxia is beneficial or harmful. Adaptation to intermittent hypoxia has been demonstrated to confer cardiovascular protection against more severe and sustained hypoxia, and, moreover, to protect against other stresses, including ischemia. Thus, the direct and cross protective effects of adaptation to intermittent hypoxia have been used for treatment and prevention of a variety of diseases and to increase efficiency of exercise training. Evidence is mounting that nitric oxide (NO) plays a central role in these adaptive mechanisms. NO-dependent protective mechanisms activated by intermittent hypoxia include stimulation of NO synthesis as well as restriction of NO overproduction. In addition, alternative, nonenzymic sources of NO and negative feedback of NO synthesis are important factors in optimizing NO concentrations. The adaptive enhancement of NO synthesis and/or availability activates or increases expression of other protective factors, including heat shock proteins, antioxidants and prostaglandins, making the protection more robust and sustained. Understanding the role of NO in mechanisms of adaptation to hypoxia will support development of therapies to prevent and treat hypoxic or ischemic damage to organs and cells and to increase adaptive capabilities of the organism.     

Effects of different acute hypoxic regimens on tissue oxygen profiles and metabolic outcomes

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. Lean and obese C57BL6 mice were exposed to 12 h of intermittent hypoxia 60 times/h (IH60) [inspired O? fraction (Fi(O?)) 21-5%, 60/h], IH 12 times/h (Fi(O?) 5% for 15 s, 12/h), sustained hypoxia (SH; Fi(O?) 10%), or normoxia while fasting. Tissue oxygen partial pressure (Pti(O?)) in liver, skeletal muscle and epididymal fat, plasma leptin, adiponectin, insulin, blood glucose, and adipose tumor necrosis factor-α (TNF-α) were measured. In lean mice, IH60 caused oxygen swings in the liver, whereas fluctuations of Pti(O?) were attenuated in muscle and abolished in fat. In obese mice, baseline liver Pti(O?) was lower than in lean mice, whereas muscle and fat Pti(O?) did not differ. During IH, Pti(O?) was similar in obese and lean mice. All hypoxic regimens caused insulin resistance. In lean mice, hypoxia significantly increased leptin, especially during SH (44-fold); IH60, but not SH, induced a 2.5- to 3-fold increase in TNF-α secretion by fat. Obesity was associated with striking increases in leptin and TNF-α, which overwhelmed effects of hypoxia. In conclusion, IH60 led to oxygen fluctuations in liver and muscle and steady hypoxia in fat. IH and SH induced insulin resistance, but inflammation was increased only by IH60 in lean mice. Obesity caused severe inflammation, which was not augmented by acute hypoxic regimens.     

Hypobaric Hypoxia Causes Body Weight Reduction in Obese Subjects

The reason for weight loss at high altitudes is largely unknown. To date, studies have been unable to differentiate between weight loss due to hypobaric hypoxia and that related to increased physical exercise. The aim of our study was to examine the effect of hypobaric hypoxia on body weight at high altitude in obese subjects. We investigated 20 male obese subjects (age 55.7 ± 4.1 years, BMI 33.7 ± 1.0 kg/m²). Body weight, waist circumference, basal metabolic rate (BMR), nutrition protocols, and objective activity parameters as well as metabolic and cardiovascular parameters, blood gas analysis, leptin, and ghrelin were determined at low altitude (LA) (Munich 530 m, D1), at the beginning and at the end of a 1‐week stay at high altitude (2,650 m, D7 and D14) and 4 weeks after returning to LA (D42). Although daily pace counting remained stable at high altitude, at D14 and D42, participants weighed significantly less and had higher BMRs than at D1. Food intake was decreased at D7. Basal leptin levels increased significantly at high altitude despite the reduction in body weight. Diastolic blood pressure was significantly lower at D7, D14, and D42 compared to D1. This study shows that obese subjects lose weight at high altitudes. This may be due to a higher metabolic rate and reduced food intake. Interestingly, leptin levels rise in high altitude despite reduced body weight. Hypobaric hypoxia seems to play a major role, although the physiological mechanisms remain unclear. Weight loss at high altitudes was associated with clinically relevant improvements in diastolic blood pressure.     

Invited review: Physiological consequences of intermittent hypoxia: systemic blood pressure.

One of the major manifestations of obstructive sleep apnea is profound and repeated hypoxia during sleep. Acute hypoxia leads to stimulation of the peripheral chemoreceptors, which in turn increases sympathetic outflow, acutely increasing blood pressure. The chronic effect of these repeated episodic or intermittent periods of hypoxia in humans is difficult to study because chronic cardiovascular changes may take many years to manifest. Rodents have been a tremendous source of information in short- and long-term studies of hypertension and other cardiovascular diseases. Recurrent short cycles of normoxia-hypoxia, when administered to rats for 35 days, allows examination of the chronic cardiovascular response to intermittent hypoxia patterned after the episodic desaturation seen in humans with sleep apnea. The result of this type of intermittent hypoxia in rats is a 10- to 14-mmHg increase in resting (unstimulated) mean blood pressure that lasts for several weeks after cessation of the daily cyclic hypoxia. Carotid body denervation, sympathetic nerve ablation, renal sympathectomy, adrenal medullectomy, and angiotensin II receptor blockade block the blood pressure increase. It appears that adrenergic and renin-angiotensin system overactivity contributes to the early chronic elevated blood pressure in rat intermittent hypoxia and perhaps to human hypertension associated with obstructive sleep apnea.     

低氧中强度训练可通过上调HIF-1α来提高机体抗氧化能力

低氧环境和运动训练均可导致人体体重降低,然而,低氧结合中强度训练对肥胖人群能量代谢及氧化应激的影响尚不清楚。本研究招募了60名无系统运动训练史的健康男性大学生,将受试者分为低氧组和常氧组,每组30名。在一个110 m^2的训练室内通过低氧训练系统模拟人工低氧环境(海拔高度:2 500 m,氧浓度:15%)。两组受试者进行1个月的低氧/常氧中强度骑行训练。此外,对低氧和常氧中强度训练的大鼠进行力竭跑台运动测试,苏木精和伊红(HE)染色评价大鼠骨骼肌形态学变化,RT-PCR检测低氧诱导因子1α(HIF-1α) mRNA的表达。研究显示,运动后低氧组的体重、脂肪重量和BMI均显著低于常氧组(p<0.05)。运动后低氧组的血清TC、HDL-C和LDL-C含量均显著低于常氧组(p<0.05),而总TG含量与常氧组无显著差异(p>0.05)。运动后,低氧组的游离脂肪酸含量显著高于常氧组(p<0.05),两组血糖无显著差异(p>0.05)。运动后,低氧组的SOD和GSH-PX水平显著高于常氧组(p<0.05),而MDA水平显著低于常氧组(p<0.05)。运动后,低氧组的IL-1β、IL-6和TNF-α水平显著低于常氧组(p<0.05)。力竭运动后,低氧组大鼠的骨骼肌形态学改变异常情况明显低于常氧组。低氧组的HIF-1αm RNA水平显著高于常氧组。本研究表明,与常氧相比,低氧中强度训练可有效降低肥胖人群的血脂水平,促进脂肪动员,减弱氧化应激损伤,抑制促炎细胞因子表达,从而促进体重减轻,并防止糖尿病、高血脂等肥胖相关疾病的发生。此外,低氧中强度可通过上调HIF-1α来提高机体抗氧化能力并减弱运动损伤。     

哺乳动物低氧应激代谢成因的研究进展

氧气是哺乳动物机体代谢稳态维持的物质基础,若代谢过程中氧气供给不足,可造成低氧应激。目前,环境低氧、代谢性低氧和携氧细胞功能障碍是造成动物低氧应激的重要成因。目前,低氧对动物机体代谢和组织功能的影响研究主要集中于肺脏、肝脏、消化道、肌肉和乳腺等部位。若处于低氧状态的哺乳动物形成了适应低氧的代谢模式,则可维持其代谢稳态;相反,若动物无法维持低氧状态下的代谢稳态,则会导致机体氧化应激甚至病变。目前,低氧应激在家畜方面的研究主要集中于高原动物代谢适应机制;然而,泌乳期动物机体代谢速率、氧气消耗和自由基水平均较高,但氧在泌乳动物代谢应激形成中的作用及其对泌乳性能的影响,仍有待探索。综述了哺乳动物产生低氧应激的代谢成因与作用结果,旨在探讨哺乳动物低氧应激生物学基础,为进一步从低氧应激调控角度为泌乳动物的健康状况维持提供理论依据。     

Influences of Normobaric Hypoxia Training on Physical Fitness and Metabolic Risk Markers in Overweight to Obese Subjects

Previous studies suggested that hypoxia and exercise may have a synergistic effect on cardiovascular and metabolic risk factors. We conducted a single blind study in overweight to obese subjects to test the hypothesis that training under hypoxia (HG, n = 24, FiO₂ = 15%) results in similar or even greater improvement in body weight and metabolic risk markers compared with exercise under normoxia (NG, n = 21, FiO₂ = 21%). After an initial metabolic evaluation including incremental exercise testing, subjects trained in normoxic or hypoxic conditions thrice weekly over a 4‐week period at a heart rate corresponding to 65% of maximum oxygen uptake (VO_2max). The experimental groups were similar at the start of the investigation and weight stable during the training period. Subjects in the hypoxia group trained at a significantly lower workload (P < 0.05). Yet, both groups showed similar improvements in VO_2max and time to exhaustion. Respiratory quotient and lactate at the anaerobic threshold as well as body composition improved more in the hypoxia group. We conclude that in obese subjects, training in hypoxia elicits a similar or even better response in terms of physical fitness, metabolic risk markers, and body composition at a lower workload. The fact that workload and, therefore, mechanic strain can be reduced in hypoxia could be particularly beneficial in obese patients with orthopedic comorbidities.     

Effect of two paradigms of chronic intermittent hypoxia on carotid body sensory activity.

Reflexes arising from the carotid bodies may play an important role in cardiorespiratory changes evoked by chronic intermittent hypoxia (CIH). In the present study, we examined whether CIH affects the hypoxic sensing ability of the carotid bodies and, if so, by what mechanisms. Experiments were performed on adult male rats (Sprague-Dawley, 250-300 g) exposed to two paradigms of CIH for 10 days: 1) multiple exposures to short durations of intermittent hypoxia per day (SDIH; 15 s of 5% O(2) + 5 min of 21% O(2), 9 episodes/h, 8 h/day) and 2) single exposure to longer durations of intermittent hypoxia per day [LDIH; 4 h of hypobaric hypoxia (0.4 atm/day) + 20 h of normoxia]. Carotid body sensory response to graded isocapnic hypoxia was examined in both groups of animals under anesthetized conditions. Hypoxic sensory response was significantly enhanced in SDIH but not in LDIH animals. Similar enhancement in hypoxic sensory response was also elicited in ex vivo carotid bodies from SDIH animals, suggesting that the effects were not secondary to cardiovascular changes. SDIH, however, had no significant effect on the hypercapnic sensory response. The effects of SDIH on the hypoxic sensory response completely reversed after SDIH animals were placed in a normoxic environment for an additional 10 days. Previous treatment with systemic administration of O(2)(-)* radical scavenger prevented SDIH-induced augmentation of the hypoxic sensory response. These results demonstrate that SDIH but not LDIH results in selective augmentation of the hypoxic response of the carotid body and O(2)(-)* radicals play an important role in SDIH-induced sensitization of the carotid body.     

Inhalation of hydrogen gas attenuates left ventricular remodeling induced by intermittent hypoxia in mice

Sleep apnea syndrome increases the risk of cardiovascular morbidity and mortality. We previously reported that intermittent hypoxia increases superoxide production in a manner dependent on nicotinamide adenine dinucleotide phosphate and accelerates adverse left ventricular (LV) remodeling. Recent studies have suggested that hydrogen (H(2)) may have an antioxidant effect by reducing hydroxyl radicals. In this study, we investigated the effects of H(2) gas inhalation on lipid metabolism and LV remodeling induced by intermittent hypoxia in mice. Male C57BL/6J mice (n = 62) were exposed to intermittent hypoxia (repetitive cycle of 1-min periods of 5 and 21% oxygen for 8 h during daytime) for 7 days. H(2) gas (1.3 vol/100 vol) was given either at the time of reoxygenation, during hypoxic conditions, or throughout the experimental period. Mice kept under normoxic conditions served as controls (n = 13). Intermittent hypoxia significantly increased plasma levels of low- and very low-density cholesterol and the amount of 4-hydroxy-2-nonenal-modified protein adducts in the LV myocardium. It also upregulated mRNA expression of tissue necrosis factor-α, interleukin-6, and brain natriuretic peptide, increased production of superoxide, and induced cardiomyocyte hypertrophy, nuclear deformity, mitochondrial degeneration, and interstitial fibrosis. H(2) gas inhalation significantly suppressed these changes induced by intermittent hypoxia. In particular, H(2) gas inhaled at the timing of reoxygenation or throughout the experiment was effective in preventing dyslipidemia and suppressing superoxide production in the LV myocardium. These results suggest that inhalation of H(2) gas was effective for reducing oxidative stress and preventing LV remodeling induced by intermittent hypoxia relevant to sleep apnea.     

Orlistat 60 mg reduces visceral adipose tissue: a 24-week randomized, placebo-controlled, multicenter trial

It is well established that abdominal obesity or upper body fat distribution is associated with increased risk of metabolic and cardiovascular disease. The purpose of the present study was to determine if a 24 week weight loss program with orlistat 60 mg in overweight subjects would produce a greater change in visceral adipose tissue (VAT) as measured by computed tomography (CT) scan, compared to placebo. The effects of orlistat 60 mg on changes in total fat mass (EchoMRI‐AH and BIA), ectopic fat (CT) and glycemic variables were assessed. One‐hundred thirty‐one subjects were randomized into a multicenter, double‐blind placebo controlled study in which 123 subjects received at least one post baseline efficacy measurement (intent‐to‐treat population). Both orlistat‐and placebo‐treated subjects significantly decreased their VAT at 24 weeks with a significantly greater loss of VAT by orlistat treated subjects (?15.7% vs. ?9.4%, P < 0.05). In addition, orlistat‐treated subjects had significantly greater weight loss (?5.93 kg vs. ?3.94 kg, P < 0.05), total fat mass loss (?4.65 kg vs. ?3.01 kg, P < 0.05) and trended to a greater loss of intermuscular adipose tissue and content of liver fat compared with placebo‐treated subjects. This is the first study to demonstrate that orlistat 60 mg significantly reduces VAT in addition to total body fat compared to placebo treated subjects after a 24 week weight loss program. These results suggest that orlistat 60 mg may be an effective weight loss tool to reduce metabolic risk factors associated with abdominal obesity.     

Addressing the Unmet Medical Need for Safe and Effective Weight Loss Therapies

Obesity is a significant healthcare problem worldwide and increases the risk of developing debilitating diseases including type 2 diabetes, cardiovascular disease, and cancer. Although the health benefits of weight reduction are well‐recognized, weight loss by diet and exercise fail in most patients, and the current marketed drugs have had limited success. It is clear that there is a significant unmet medical need for safe and effective weight‐reducing agents. In this review, the current status of potential weight loss approaches that are in development by the pharmaceutical and biotechnology industry are discussed. This should lead to novel treatments that can be used long‐term to effectively treat this serious metabolic disorder.     

Invited review: Physiological and pathophysiological responses to intermittent hypoxia.

This mini-review summarizes the physiological adaptations to and pathophysiological consequences of intermittent hypoxia with special emphasis given to the pathophysiology associated with obstructive sleep apnea. Intermittent hypoxia is an effective stimulus for evoking the respiratory, cardiovascular, and metabolic adaptations normally associated with continuous chronic hypoxia. These adaptations are thought by some to be beneficial in that they may provide protection against disease as well as improve exercise performance in athletes. The long-term consequences of chronic intermittent hypoxia may have detrimental effects, including hypertension, cerebral and coronary vascular problems, developmental and neurocognitive deficits, and neurodegeneration due to the cumulative effects of persistent bouts of hypoxia. Emphasis is placed on reviewing the available data on intermittent hypoxia, making extensions from applicable information from acute and chronic hypoxia studies, and pointing out major gaps in information linking the genomic and cellular responses to intermittent hypoxia with physiological or pathophysiological responses.     

Metabolic Fitness in Active Reduced-Obese Individuals

TREMBLAY, ANGELO, ERIC DOUCET, PASCAL IMBEAULT, PASCALE MAURIÈGE, JEAN-PIERRE DESPRÉS, AND DENIS RICHARD. Metabolic fitness in active reduced-obese individuals. Obes Res. Objective: To verify whether a physical activity-low-fat diet follow-up could normalize the metabolic risk profile of reduced-obese men and women having undergone considerable weight loss through energy restriction and drug therapy. Research Methods and Procedures: Twenty obese individuals (12 men, 8 women) participated in a weight-reducing program that included two phases. In the first phase, a non-macronutrient-specific dietary restriction of about 700 kcal/day was prescribed to induce weight loss over 15 weeks, with either fenfluramine or placebo. The second phase consisted of a physical activity-low-fat diet follow-up that was maintained as long as subjects did not experience resistance to further body weight and fat loss. Resistance to lose fat occurred after a mean cumulative fat loss of 14 and 8 kg in men and women, respectively. Results: Despite this substantial decrease in body fat, subjects' adiposity remained much higher at the end of this protocol than values observed in lean control subjects. However, fasting plasma levels of insulin, cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and triglyceride as well as the response of insulin and glucose to oral glucose were normalized at the end of the physical activity-low-fat diet follow-up. Discussion: These results indicate that further weight and fat losses may not be justified when a moderate body weight loss resulting in a highly favorable improvement of metabolic risk profile is achieved in patients who would have still been diagnosed as overweight or obese on the basis of criteria currently promoted by public health agencies.     

Effect of mild intermittent hypoxia on glucose tolerance, muscle morphology and AMPK-PGC-1alpha signaling

The main goal of this study was to investigate the long-term effect of daily 8-hour mild intermittent hypoxia (14-15% O2) on glucose tolerance and muscle morphology of Sprague-Dawley rats. The involvement of AMPK-PGC-1alpha-VEGF signaling pathways in the skeletal muscle was also determined during the first 8 hours of hypoxia. We found that mRNA levels of VEGF and PGC-1alpha were significantly increased above control after 8-h mild hypoxia without a change in AMPK phosphorylation. After 8 weeks of mild intermittent hypoxia treatment, plasma glucose and insulin levels in oral glucose tolerance test (OGTT), epididymal fat mass, and body weight were significantly lower compared to the control group. While soleus muscle weight was not changed, capillary and fiber densities in the hypoxia group were 33% and 35% above the control suggesting reorganization of muscle fibers. In conclusion, our data provide strong evidence that long-term mild intermittent hypoxia decreases the diffusion distance of glucose and insulin across muscle fibers, and decreases adiposity in rats. These changes may account for the improved glucose tolerance observed following the 8-week hypoxia treatment, and provides grounds for investigating the development of a mild non-pharmacological intervention in the treatment of obesity and type 2 diabetes.     

Lipophilic Environmental Chemical Mixtures Released During Weight-Loss: The Need to Consider Dynamics

Intentional weight loss can increase health risk in the long-term, despite short-term benefits, because human adipose tissue is widely contaminated with various lipophilic environmental contaminants, especially persistent organic pollutants (POPs). Recently, chronic exposure to low POPs has emerged as a new risk factor for common metabolic diseases and cardiovascular diseases. The amount of POPs released from adipocytes to the circulation increases during weight loss, thereby increasing POPs exposure of other critical organs. Possible harmful effects due to release of POPs during weight loss are opposite to those usually expected from losing weight. It is speculated that this tradeoff can explain recent puzzling findings on intensive weight loss. The presence of POPs in adipose tissue adds a challenge to weight management and an optimal strategy of weight management needs to consider both fat mass and dynamics of POPs.