Light intensity alters the effects of light-induced circadian disruption on glucose and lipid metabolism in mice.

Circadian disruption induced by rotating light cycles has been linked to metabolic disorders. However, how the interaction of light intensity and light cycle affects metabolism under different diets remains to be explored. Eighty mice were first randomly stratified into the low-fat diet (LFD, n = 40) or high-fat diet (HFD, n = 40) groups. Each group was further randomly subdivided into four groups (n = 8-12 per group) in terms of different light intensities [lower (LI, 78 lx) or higher intensity (HI, 169 lx)] and light cycles [12-h light:12-h dark cycle or circadian-disrupting (CD) light cycle consisting of repeated 6-h light phase advancement]. Body weight was measured weekly. At the end of the 16-wk experiment, mice were euthanized for serum and pathological analysis. Glucose and insulin tolerance tests were performed during the last 2 wk. The CD cycle increased body weight gain, adipocyte area, glucose intolerance, and insulin resistance of LFD as well as HFD mice under HI but not LI condition. Moreover, the serum and hepatic triglyceride levels increased with LFD-HI treatment, regardless of light cycle. In addition, the CD cycle improved lipid and glucose metabolism under HFD-LI condition. In summary, the detrimental effects of the CD cycle on metabolism were alleviated under LI condition, especially in HFD mice. These results indicate that modulating light intensity is a potential strategy to prevent the negative metabolic consequences associated with jet lag or shift work.NEW & NOTEWORTHY Glucose and lipid homeostasis is altered by the CD cycles in a light-intensity-dependent manner. Lower-intensity light reverses the negative metabolic effects of the CD cycles, especially under HFD feeding. The interaction of light intensity and light cycle on metabolism is independent of energy intake and eating pattern. Glucose metabolic disorders caused by rotating light cycles occur along with compensatory ß-cell mass expansion.

Effect of a high-calorie diet and constant light exposure on female reproduction, metabolism and immune inflammation: A comparative study of different mouse models.

PROBLEM: Excess caloric intake and irregular circadian rhythm could severely impair female reproductive, metabolic, and immune function. However, the similarities and differences between their individual and combined effects and mechanisms have not been fully elucidated. Due to limitations and confounding factors in clinical research, we used these two kinds of unhealthy factors to intervene the mice singly or in combination to explore their effects on individuals. METHOD OF STUDY: We used a high-calorie diet (HCD), constant light exposure (CLE), and a high-calorie diet combined with constant light exposure (HCD + CLE) to build three different mouse models. During the 9 weeks modeling period, the estrous cycles were monitored, and after modeling, the indicators of glycolipid metabolism, inflammation, and reproductive endocrine function were tested. RESULTS: We found that both HCD and CLE alone could induce ovulatory disorders, obesity, and chronic low-grade inflammation and inhibit melatonin secretion. The difference was that HCD significantly reduced the serum luteinizing hormone (LH) and testosterone (T) levels, inhibited the expression of FSH ß and LH ß in pituitary, increased cytochrome P450 enzymes and LH receptor expression in ovary, as well causing impaired glucose tolerance and hyperlipidemia, and significantly promoted the secretion of leptin and inhibited the secretion of adiponectin. However, CLE significantly increased blood LH and T, prompted the expression of kisspeptin in hypothalamus and LH ß in pituitary, and had no effect on glycolipid metabolic indexes or the secretion of leptin or adiponectin. The phenotype of HCD + CLE model was basically the same as that of HCD model, associated with more severe visceral obesity and chronic inflammation. CONCLUSIONS: In conclusion, we found that unhealthy lifestyle determines the phenotype of reproductive endocrine, immune, and metabolic disorders. These findings can provide theoretical support for the subsequent study of PCOS-like features.

Targeted peripheral focused ultrasound stimulation attenuates obesity-induced metabolic and inflammatory dysfunctions.

Obesity, a growing health concern, is associated with an increased risk of morbidity and mortality. Chronic low-grade inflammation is implicated in obesity-driven metabolic complications. Peripheral focused ultrasound stimulation (pFUS) is an emerging non-invasive technology that modulates inflammation. Here, we reasoned that focused ultrasound stimulation of the liver may alleviate obesity-related inflammation and other comorbidities. After 8 weeks on a high-fat high-carbohydrate "Western" diet, C57BL/6J mice were subjected to either sham stimulation or focused ultrasound stimulation at the porta hepatis. Daily liver-focused ultrasound stimulation for 8 weeks significantly decreased body weight, circulating lipids and mitigated dysregulation of adipokines. In addition, liver-focused ultrasound stimulation significantly reduced hepatic cytokine levels and leukocyte infiltration. Our findings demonstrate the efficacy of hepatic focused ultrasound for alleviating obesity and obesity-associated complications in mice. These findings suggest a previously unrecognized potential of hepatic focused ultrasound as a possible novel noninvasive approach in the context of obesity.

PPARα mediates night neon light-induced weight gain: role of lipid homeostasis.

Rationale: Light pollution leads to high risk of obesity but the underlying mechanism is not known except for the influence of altered circadian rhythm. Peroxisome proliferator-activated receptor α (PPARα) regulates lipid metabolism, but its role in circadian-related obesity is not clear. Methods: Wild-type (WT) and Ppara-null (KO) mice on a high-fat diet (HFD) were treated with neon light at night for 6 weeks. Body weights were recorded and diet consumption measured. The hypothalamus, liver, adipose and serum were collected for mechanism experimentation. Results: WT mice on a HFD and exposed to night neon light gained about 19% body weight more than the WT control mice without light exposure and KO control mice on a HFD and exposed to night neon light. The increase in adipose tissue weight and adipocyte size led to the differences in body weights. Biochemical analysis suggested increased hepatic lipid accumulated and increased transport of lipid from the liver to peripheral tissues in the WT mice that gained weight under neon light exposure. Unlike KO mice, the expression of genes involved in lipid metabolism and the circadian factor circadian locomotor output cycles kaput (CLOCK) in both liver and adipose tissues were elevated in WT mice under neon light exposure. Conclusions: PPARα mediated weight gain of HFD-treated mice exposed to night neon light. More lipids were synthesized in the liver and transported to peripheral tissue leading to adaptive metabolism and lipid deposition in the adipose tissue. These data revealed an important mechanism of obesity induced by artificial light pollution where PPARα was implicated.

Photoperiodic effects on somatic growth and gonadal maturation in Mickey Mouse platy, Xiphophorus maculatus (Gunther, 1866).

Photoperiod is important in initiation or suppression of reproductive timing and gonadal maturation which varies with species. The aim of the present study was to investigate the effect of two photoperiodic manipulating regimes, i.e., long (18L:6D) and short (10L:14D) photoperiods for a period of 60 days on somatic growth and gonadal maturation of a live-bearer ornamental fish, Mickey Mouse platy (Xiphophorus maculatus). The control fish were further kept under the laboratory environmental condition. The results showed a significant increase in weight gain, specific growth rate, and gonadosomatic index in fish under long photoperiod than those exposed to short photoperiod and control condition (P < 0.05). A condition factor showed significant variations between long photoperiod and control groups. Furthermore, a long photoperiod also induced a significant increase in the number of fish with mature embryo and middle-eyed embryo in the ovary. Similarly, histological analysis of testes of males showed an increase in the number of mature spermatid and spermatozoa under long photoperiod when compared to those of control and short photoperiod ones. Thus, it can be concluded that long-day photoperiodic manipulation may be applied for healthy growth and early gonadal maturation of live-bearer ornamental fishes.

Early weight gain predicts treatment response in adolescents with anorexia nervosa enrolled in a family-based partial hospitalization program.

OBJECTIVE: Improved treatment outcome in family-based treatment (FBT) for anorexia nervosa (AN) is predicted by weight gain occurring early in the course of treatment (i.e., about 4 lbs by week 4). Although prior work suggests that early weight gain in higher levels of care (e.g., partial hospitalization programs [PHP]) predicts weight restoration at discharge, no study has examined the specific rate of gain within FBT-informed PHP programs that best predicts treatment response. METHOD: This study examined rate of weight gain in pounds and percent expected body weight (EBW) that predicts positive outcome in 70 patients (M age = 15.49 years, SD = 2.56) with AN who were enrolled in a family-based PHP. RESULTS: Receiver operator characteristic analyses demonstrated that changes in %EBW during weeks 2-5 were more useful than changes in weight in predicting positive outcome. Gaining at least 8.9 pounds or over 8% of EBW in the first 4 weeks of treatment significantly predicted positive outcome. DISCUSSION: Findings suggest that positive outcome in an FBT-informed PHP is predicted by rapid weight gain in the initial weeks of treatment. Research is needed to identify specific family and patient characteristics that facilitate weight gain and to develop corresponding interventions to improve outcome.

Melatonin Orchestrates Lipid Homeostasis through the Hepatointestinal Circadian Clock and Microbiota during Constant Light Exposure.

Misalignment between natural light rhythm and modern life activities induces disruption of the circadian rhythm. It is mainly evident that light at night (LAN) interferes with the human endocrine system and contributes to the increasing rates of obesity and lipid metabolic disease. Maintaining hepatointestinal circadian homeostasis is vital for improving lipid homeostasis. Melatonin is a chronobiotic substance that plays a main role in stabilizing bodily rhythm and has shown beneficial effects in protecting against obesity. Based on the dual effect of circadian rhythm regulation and antiobesity, we tested the effect of melatonin in mice under constant light exposure. Exposure to 24-h constant light (LL) increased weight and insulin resistance compared with those of the control group (12-h light-12-h dark cycle, LD), and simultaneous supplementation in the melatonin group (LLM) ameliorated this phenotype. Constant light exposure disturbed the expression pattern of a series of transcripts, including lipid metabolism, circadian regulation and nuclear receptors in the liver. Melatonin also showed beneficial effects in improving lipid metabolism and circadian rhythm homeostasis. Furthermore, the LL group had increased absorption and digestion of lipids in the intestine as evidenced by the elevated influx of lipids in the duodenum and decrease in the efflux of lipids in the jejunum. More interestingly, melatonin ameliorated the gut microbiota dysbiosis and improved lipid efflux from the intestine. Thus, these findings offer a novel clue regarding the obesity-promoting effect attributed to LAN and suggest a possibility for obesity therapy by melatonin in which melatonin could ameliorate rhythm disorder and intestinal dysbiosis.

Changes in feed consumption and water intake among broiler chickens subjected to melatonin treatment during the hot-dry season.

The experiment was conducted to evaluate changes in feed consumption and water intake among broiler chickens subjected to melatonin treatment during the hot-dry season. A total of 300 broiler chicks were selected and assigned into three groups, by simple random sampling, comprising 100 chicks each: group I was exposed to natural photoperiod of about 12-h light and 12-h darkness cycle (12D/12L), without melatonin supplementation; group II was kept under 24-h continuous lighting (CL), without melatonin supplementation; and group III was raised under 24-h CL and administered daily with melatonin orally at 0.5 mg/kg (CL + MEL). Live weight (LW), feed consumption, and water intake for each group were obtained at weekly intervals over a period of 8 weeks. On day 42 of age, the LW of 2420 ± 50 g/bird was obtained in group III administered with melatonin (CL + MEL), while LW values recorded in the 12D/12L and CL groups not administered with melatonin were 1470.00 ± 30.00 and 1907.00 ± 38.00 g/bird, respectively. The mean weight gain in CL + MEL (345.00 ± 21.01 g) was significantly (P < 0.05) higher than those of the 12D/12L (244.99 ± 18.67 g) and CL (307.48 ± 18.14 g) groups. Feed consumptions were significantly (P < 0.05) different in all the groups. Group II, raised on CL without melatonin supplementation, had the highest feed consumption value of 25.14 ± 0.51 g/bird from day 14, and attained the peak value of 206.77 ± 7.82 g/bird at day 56. The highest overall amount of water intake was recorded in the melatonin-treated group. In conclusion, melatonin administration to broiler chickens enhanced water intake but decreased feed consumption with increase in LW during the hot-dry season.

Exposure to solar ultraviolet radiation limits diet-induced weight gain, increases liver triglycerides and prevents the early signs of cardiovascular disease in mice.

BACKGROUND AND AIMS: Sunlight exposure is associated with a number of health benefits including protecting us from autoimmunity, cardiovascular disease, obesity and diabetes. Animal studies have confirmed that ultraviolet (UV)-B radiation, independently of vitamin D, can limit diet-induced obesity, metabolic syndrome and atherosclerosis. The aim of this study is to investigate whether exposure to the UV radiation contained in sunlight impacts on these disease parameters. METHODS AND RESULTS: We have trialled an intervention with solar UV in obese and atherosclerosis-prone mice. We have discovered that solar-simulated UV can significantly limit diet-induced obesity and reduce atheroma development in mice fed a diet high in sugar and fat. The optimal regime for this benefit was exposure once a week to solar UV equivalent to approximately 30 min of summer sun. Exposure to this optimal dose of solar UV also led to a significant increase in liver triglycerides which may protect the liver from damage. CONCLUSION: Our results show that the UV contained in sunlight has the potential to prevent and treat chronic disease at sites distant from irradiated skin. A major health challenge going forward will be to harness the power of the sun safely, without risking an increase in skin cancers.

Noise-induced sleep disruption increases weight gain and decreases energy metabolism in female rats.

BACKGROUND/OBJECTIVES: Inadequate sleep increases obesity and environmental noise contributes to poor sleep. However, women may be more vulnerable to noise and hence more susceptible to sleep disruption-induced weight gain than men. In male rats, exposure to environmental (i.e. ambient) noise disrupts sleep and increases feeding and weight gain. However, the effects of environmental noise on sleep and weight gain in female rats are unknown. Thus, this study was designed to determine whether noise exposure would disturb sleep, increase feeding and weight gain and alter the length of the estrous cycle in female rats. SUBJECTS/METHODS: Female rats (12 weeks old) were exposed to noise for 17d (8 h/d during the light period) to determine the effects of noise on weight gain and food intake. In a separate set of females, estrous cycle phase and length, EEG, EMG, spontaneous physical activity and energy expenditure were recorded continuously for 27d during baseline (control, 9d), noise exposure (8 h/d, 9d) and recovery (9d) from sleep disruption. RESULTS: Noise exposure significantly increased weight gain and food intake compared to females that slept undisturbed. Noise also significantly increased wakefulness, reduced sleep and resulted in rebound sleep during the recovery period. Total energy expenditure was significantly lower during both noise exposure and recovery due to lower energy expenditure during spontaneous physical activity and sleep. Notably, noise did not alter the estrous cycle length. CONCLUSIONS: As previously observed in male rats, noise exposure disrupted sleep and increased weight gain in females but did not alter the length of the estrous cycle. This is the first demonstration of weight gain in female rats during sleep disruption. We conclude that the sleep disruption caused by exposure to environmental noise is a significant tool for determining how sleep loss contributes to obesity in females.

Effect of radioactive iodine-induced hypothyroidism on longitudinal bone growth during puberty in immature female rats.

Thyroid cancer in children, the most common endocrine malignancy, shows aggressive behavior and has a high recurrence rate after surgical ablation. Radioactive iodine (RAI) treatment is the most effective primary modality for medical ablation of juvenile thyroid cancer, and leads to intentional hypothyroidism. Although several negative impacts of hypothyroidism have been reported in children in response to other antithyroid agents, the combined effects of RAI exposure and hypothyroidism, on growing bones specifically, are unknown. In this study, we investigated the effect of RAI-induced hypothyroidism on the long bones during the pubertal growth spurt using immature female rats. Female Sprague-Dawley rats were randomly divided into a control group, and an RAI-treated group fed with RAI (0.37 MBq/g body weight) twice via gavage. After 4 weeks, we observed a significantly-reduced serum free thyroxine level in the RAI group. The latter group also displayed decreased body weight gain compared to the control. In addition, the lengths of long bones, such as the leg bones and vertebral column, as well as bone mineral content, were reduced in the RAI-treated animals. Our results confirm the negative impacts of RAI-induced thyroid deficiency during puberty on longitudinal bone growth and bone mineralization.

Constant light during lactation programs circadian and metabolic systems.

Exposure to light at night is a disruptive condition for the adult circadian system, leading to arrhythmicity in nocturnal rodents. Circadian disruption is a risk factor for developing physiological and behavioral alterations, including weight gain and metabolic disease. During early stages of development, the circadian system undergoes a critical period of adjustment, and it is especially vulnerable to altered lighting conditions that may program its function, leading to long-term effects. We hypothesized that during lactation a disrupted light-dark cycle due to light at night may disrupt the circadian system and in the long term induce metabolic disorders. Here we explored in pups, short- and long-term effects of constant light (LL) during lactation. In the short term, LL caused a loss of rhythmicity and a reduction in the immunopositive cells of VIP, AVP, and PER1 in the suprachiasmatic nucleus (SCN). In the short term, the affection on the circadian clock in the pups resulted in body weight gain, loss of daily rhythms in general activity, plasma glucose and triglycerides (TG). Importantly, the DD conditions during development also induced altered daily rhythms in general activity and in the SCN. Exposure to LD conditions after lactation did not restore rhythmicity in the SCN, and the number of immunopositve cells to VIP, AVP, and PER1 remained reduced. In the long term, daily rhythmicity in general activity was restored; however, daily rhythms in glucose and TG remained disrupted, and daily mean levels of TG were significantly increased. Present results point out the programming role played by the LD cycle during early development in the function of the circadian system and on metabolism. This study points out the risk represented by exposure to an altered light-dark cycle during early stages of development. ABBREVIATIONS: AVP: arginine vasopressin peptide; CRY: cryptochrome; DD: constant darkness; DM: dorsomedial; LD: light-dark cycle; LL: constant light; NICUs: neonatal intensive care units; P: postnatal days; PER: period; S.E.M.: standard error of the mean; SCN: suprachiasmatic nucleus; TG: triglycerides; VIP: vasointestinal peptide; VL: ventrolateral; ZT: zeitgeber time.

Rat sensorimotor cortex tolerance to parallel transections induced by synchrotron-generated X-ray microbeams.

Microbeam radiation therapy is a novel preclinical technique, which uses synchrotron-generated X-rays for the treatment of brain tumours and drug-resistant epilepsies. In order to safely translate this approach to humans, a more in-depth knowledge of the long-term radiobiology of microbeams in healthy tissues is required. We report here the result of the characterization of the rat sensorimotor cortex tolerance to microradiosurgical parallel transections. Healthy adult male Wistar rats underwent irradiation with arrays of parallel microbeams. Beam thickness, spacing and incident dose were 100 or 600 µm, 400 or 1200 µm and 360 or 150 Gy, respectively. Motor performance was carried over a 3-month period. Three months after irradiation rats were sacrificed to evaluate the effects of irradiation on brain tissues by histology and immunohistochemistry. Microbeam irradiation of sensorimotor cortex did not affect weight gain and motor performance. No gross signs of paralysis or paresis were also observed. The cortical architecture was not altered, despite the presence of cell death along the irradiation path. Reactive gliosis was evident in the microbeam path of rats irradiated with 150 Gy, whereas no increase was observed in rats irradiated with 360 Gy.

Effects of subchronic extremely low-frequency electromagnetic field exposure on biochemical parameters in rats.

The objective of the present study was to systematically determine the effects of 50 Hertz (Hz) magnetic fields (MFs) on biochemical parameters in rats. Sixty-four adult (5 weeks old, 140-165 g) male Sprague-Dawley rats were randomly divided into four groups: sham, 20 µTesla (µT), 100 µT, and 500 µT 50 Hz MF ( n = 16 in each group). The rats in the MF groups were exposed for 2 h daily for up to 4 weeks. Under these experimental conditions, body weight, organ coefficients, biochemical parameters (blood lipids, myocardial enzymes, liver function, and renal function) were measured. We found that 50 Hz MFs had no significant effects on growth or on the majority of blood biochemical parameters, with the exception of creatinine and cholesterol. However, the changes in creatinine and cholesterol were relatively small and unlikely to be clinically relevant.

Fractionation Spares Mice From Radiation-Induced Reductions in Weight Gain But Does Not Prevent Late Oligodendrocyte Lineage Side Effects.

PURPOSE: To determine the late effects of fractionated versus single-dose cranial radiation on murine white matter. METHODS AND MATERIALS: Mice were exposed to 0 Gy, 6 × 6 Gy, or 1 × 20 Gy cranial irradiation at 10 to 12 weeks of age. Endpoints were assessed through 18 months from exposure using immunohistochemistry, electron microscopy, and electrophysiology. RESULTS: Weight gain was temporarily reduced after irradiation; greater loss was seen after single versus fractionated doses. Oligodendrocyte progenitor cells were reduced early and late after both single and fractionated irradiation. Both protocols also increased myelin g-ratio, reduced the number of nodes of Ranvier, and promoted a shift in the proportion of small, unmyelinated versus large, myelinated axon fibers. CONCLUSIONS: Fractionation does not adequately spare normal white matter from late radiation side effects.

Degenerative Tissue Responses to Space-like Radiation Doses in a Rodent Model of Simulated Microgravity.

This study examines acute and degenerative tissue responses to space-like radiation doses in a rodent model of simulated microgravity. We have studied four groups of rats, control (CON), irradiated (IR), irradiated and hindlimb suspended (IR-HLS), and suspended (HLS) that were maintained for two weeks. IR and IR+HLS groups were exposed to five sessions of X-ray irradiation (1.2 Gy each, at 3-4 days intervals). Body weights, soleus muscle weights, and hindlimb bone mineral density (BMD) were measured. Results show that compared to CON animals, IR, HLS, and IR+HLS group reduced the body weight gain significantly. IR-associated growth retardation appeared to be closely linked to acute and transient post-IR 'anorexia' (a decrease in food intake). HLS but not IR induced major changes in the musculoskeletal system, consisting in decreases in soleus muscle mass and bone mineral density of distal femur and proximal tibia. Additional dosimetric studies showed that the effect of IR on weight is detectable at 0.3 Gy X-ray doses, while no threshold dose for the IR-produced decrease in food intake could be observed. This study suggests that space flight-associated anorexia and musculoskeletal degenerative changes may be driven by different, radiation- and microgravity-associated (respectively) mechanisms.

Lighting schedule and dimming period in early life: consequences for broiler chicken leg bone development.

Prolonged (>20 h) light periods during grow-out of broiler chickens have been shown to increase the occurrence of skeletal abnormalities, but the effects of early life light-dark schedules are not well known. The present experiment investigated the effect of lighting schedule and light-dark transition during the first days of a broiler chicken's life on leg bone development. In 2 experiments, Ross-308 broiler chicks (n = 2,500 per experiment) were subjected to 1 of 5 treatments for 4 d: 24L; 2L:1D lighting schedule with either an abrupt or gradual light-dark transition ("dimming"); and a 2L:6D lighting schedule with an abrupt transition or dimming. At d 4, tibia and femur weight, length, and diameter, yolk free body mass, organ weights, realized weight gain, feed intake, feed conversion ratio, and mortality were determined. In Experiment 2, chick length and relative asymmetry of the femur and tibia were determined additionally. Data were analyzed using orthogonal contrasts. 24L resulted in higher femur diameter (P<0.028; both experiments), tibia diameter (P<0.001; Experiment 1), relative asymmetry of tibia length (P=0.002; Experiment 2), and relative asymmetry of femur length (P=0.003) than applying a light-dark schedule. A 2L:1D lighting schedule resulted in higher femur length (P=0.039; Experiment 1) and relative asymmetry of tibia length (P=0.032; Experiment 2) and lower relative asymmetry of tibia diameter (P=0.016) than a 2L:6D lighting schedule. An abrupt light-dark transition resulted in higher relative asymmetry of tibia length (P=0.004; Experiment 2) and relative asymmetry of tibia diameter (P=0.018) than dimming. To conclude, leg bone development in the first 4 d of a broiler chicken's life was higher for 24L than when a lighting schedule was applied, but relative asymmetry was higher as well, suggesting developmental instability. The effect of dimming on leg bone development was less pronounced, but the decreased relative asymmetry levels in the dimming treatment suggested lower environmental stress than for the abrupt light-dark transition.

Metabolic changes in serum steroids induced by total-body irradiation of female C57B/6 mice.

The short- and long-term effects of a single exposure to gamma radiation on steroid metabolism were investigated in mice. Gas chromatography-mass spectrometry was used to generate quantitative profiles of serum steroid levels in mice that had undergone total-body irradiation (TBI) at doses of 0Gy, 1Gy, and 4Gy. Following TBI, serum samples were collected at the pre-dose time point and 1, 3, 6, and 9 months after TBI. Serum levels of progestins, progesterone, 5ß-DHP, 5α-DHP, and 20α-DHP showed a significant down-regulation following short-term exposure to 4Gy, with the exception of 20α-DHP, which was significantly decreased at each of the time points measured. The corticosteroids 5α-THDOC and 5α-DHB were significantly elevated at each of the time points measured after exposure to either 1 or 4Gy. Among the sterols, 24S-OH-cholestoerol showed a dose-related elevation after irradiation that reached significance in the high dose group at the 6- and 9-month time points.

Light rhythm and diet differently influence facets of the metabolic syndrome in WOKW rats.

It has previously been shown that high-calorie diet alters the function of the mammalian circadian clock and that obesity has an influence on circadian organization of hormone secretion. That prompted us to test whether inbred Wistar Ottawa Karlsburg W (RT1(u)) (WOKW) rats developing facets of the metabolic syndrome show changes in their metabolic profiles under different feeding conditions (high-fat, high-sugar versus control diet) and under two different 12 h:12 h light-dark (LD) cycles. At the age of four weeks, these rats were divided into four groups. Groups 1 and 2 were kept under initial LD cycle (lights on at 05:00 h). Group 1 was fed with a normal rat diet while group 2 received a high-fat, high-sugar diet from 10 up to the age of 21 weeks. Groups 3 and 4 were kept under a shifted LD cycle (lights on at 11:00 h). Group 3 was given a normal diet while group 4 received a high-fat, high-sugar diet from an age like groups 1 and 2. Several metabolic traits were studied during the observation period of 21 weeks. The blood samples were obtained 2 h before lights off. Body weight gain (P < 0.001), leptin (P < 0.001), triglycerides (P < 0.001) and cholesterol (P < 0.05) were significantly reduced in group 4 versus group 2, but comparable between control groups (1 versus 3). The insulin concentrations were reduced in groups 3 and 4 versus groups 1 and 2 without effect of diet. In conclusion, the results provide evidence that light conditions influence diet induced changes in phenotypic traits like body weight gain, lipids as well as hormone levels (insulin and leptin) in WOKW rats.

Prognostic significance of weight gain during definitive chemoradiotherapy for locally advanced non-small-cell lung cancer.

BACKGROUND: The successful treatment of locally advanced non-small-cell lung cancer (NSCLC) with chemoradiotherapy (CRT) is still compromised by poor locoregional and distant control rates. Given the morbidity associated with treatment, it is critical to determine clinical prognostic factors to risk stratify patients before and after aggressive therapy. This study aimed to discern the prognostic value of weight gain during CRT in patients with locally advanced NSCLC. PATIENTS AND METHODS: This was a retrospective analysis of 92 patients treated with definitive split-course CRT between 2004 and 2010 at Rush University Medical Center. Weight gain was defined as a weight change greater than the highest quartile of change between the start and finish of CRT (4.5 lb). Overall survival (OS), locoregional progression-free survival (PFS), and distant metastasis-free survival (DMFS) were determined using Kaplan-Meier analysis, and the cumulative incidences of locoregional and distant recurrence were calculated. Cox regression (multivariate analysis) was used to determine independent predictors of OS. RESULTS: With a median follow-up of 50 months for surviving patients, the median, 3- and 5-year OS probabilities were 25 months, 37%, and 29%, respectively. The 3-year cumulative risks of locoregional and distant metastases were 51% and 64%. Patients who experienced weight gain were significantly more likely to survive (3-year OS, 55% vs. 31%; P = .04) and prolonged DMFS resulted. Weight gain was the only significant predictor of survival on multivariate analysis. CONCLUSIONS: Weight gain during split-course CRT was associated with superior OS and DMFS. The presence of weight gain may have utility in risk stratification after CRT as well as in identifying novel treatment approaches for patients with locally advanced NSCLC.