Repeated light-dark shifts speed up body weight gain in male F344 rats
Ling-Ling Tsai,1
Yu-Che Tsai,1
Kai Hwang,1
Yu-Wen Huang,2 and
Jeh-En Tzeng3
1Department of Psychology, National Chung-Cheng University and Departments of 2Laboratory Medicine and 3Pathology, Buddhist Dalin Tzu Chi General Hospital, Chia-yi, Taiwan, Republic of China
Submitted 20 December 2004
; accepted in final form 28 February 2005
 |
ABSTRACT
|
---|
This study is aimed at verifying the causal relationship of chronic circadian desynchronization and changes in body weight control. Eight male albino F344 rats aged between 1215 wk were subjected to twice weekly 12-h shifts of the daily light-dark (LD) cycle for 13 wk (3 mo). Continuous circadian phase shifts consisting of intermittent phase delay and advance and reduced circadian amplitudes were consistently displayed in all five experimental rats implanted intraperitoneally with heart rate, body temperature, and activity transponders. The experimental rat maintained a greater body weight during LD shifts and even after 10 days of recovery than that of the age-matched control rat, which was maintained on a regular LD cycle. Body weight gain was greater in the first 2 mo of LD shifts in the experimental rat than in the control rat. Relative to the baseline, food intake and activity percentages were increased and reduced, respectively, for the experimental rats. Features of these results, such as increased body weight gain and food intake, and reduced activity, suggest a causal relationship of chronic circadian desynchronization and changes in body weight control in male albino F344 rats.
shift work; circadian rhythm; reentrainment; energy regulation
ACUTE PERTURBATIONSof the circadian rhythm structure like the transmeridian flights and the shifts of working schedules are related to the so-called "jet lag" and "shift lag" syndrome, respectively, both of which are characterized by feelings of malaise, fatigue, sleepiness, insomnia, digestive troubles, irritability, impaired mental agility, and performance efficiency (3). These symptoms often last for a short term, and they disappear after several days of stay at the local time for the jet lag and during the day shifts for the shift lag. Long-term disruptions of circadian rhythms, like chronic shift work, are associated with several medical diseases. Cardiovascular diseases, gastrointestinal disorders, and negative pregnancy outcomes have been reported to be more common in shift workers than in day workers in several epidemiological studies (12, 24, 25). The mechanisms that are responsible for the association between work shifts and each disease are unclear. In addition to circadian rhythm and sleep factors, however, behavioral changes and social disturbances are also considered to be involved in disease mechanisms (11, 12) and coping ability of shift workers (17).
In most industrialized countries, cardiovascular diseases are the leading cause of death and disability. Bøggild and Knutsson (2) reviewed 17 studies and concluded that, compared with day workers, shift workers have a 40% increase in risk of cardiovascular disease. Conventional risk factors for cardiovascular disease are related mainly to metabolic syndrome, including obesity, elevated serum total and low-density lipoprotein (LDL) cholesterol, low high-density lipoprotein (HDL)-cholesterol, elevated triglycerides, and impaired glucose tolerance. Previous survey studies show that the current work shift status is related to elevated weight gain (5), body mass index (BMI; see Refs. 4, 7, 9, and 23), waist-to-hip ratio (WHR; see Ref. 23), and prevalence of overweight (20) and of obesity (4, 8). Furthermore, positive correlations of BMI (9, 21, 27), WHR (27), and prevalence of overweight (20) with duration of work shift have been reported. Elevated serum total cholesterol and prevalence of high serum triglycerides and of low HDL-cholesterol in shift workers have been reported in a population-based study of 27,485 people (8). Nonetheless, inconsistent results have also been reported in BMI (e.g., see Ref. 18), WHR (e.g., see Ref. 4), and serum cholesterol and triglycerides (reviewed in Ref. 2) for shift workers. Methodological problems related to duration and type of work shift, demographic variations between shift workers and reference groups, and even the timing of blood sampling, etc., could all lead to variant results (2).
Experimental work shift studies have been done in human subjects but only for a short period (e.g., see Ref. 10). The causal relationship of long-term circadian rhythm disturbances and changes in physiological systems has been studied in laboratory rodents undergoing a 12-h phase shift in the light-dark (LD) cycle on a weekly basis (13, 14, 19, 22). Body weight is lower in female Brown Norway rats (14) and female CD2F1 mice (19) subjected to weekly shifts in LD cycle. In contrast to most rat strains, e.g., Sprague-Dawley, bred in standard laboratory conditions, F344 rats are excellent in self-regulating their energy intake to maintain a lower body weight gain after maturity (15). The present study applied 12-h phase shifts in LD cycle two times per week to male F344 rats and found higher body weight gain in the experimental rats than in the controls rats. The relationship of food intake and activity level to repeated LD shifts was examined as well.
 |
METHODS
|
---|
Subjects.
Specific pathogen-free, male inbred F344 rats (F344/N) aged 68 wk were purchased from the National Laboratory of Animal Breeding and Research Center (Taipei, Taiwan, R.O.C.). Rats were randomly assigned to experimental (LS) and control (LC) groups. Eight age-matched LS-LC rat pairs were used, and each pair was studied at the same time. Five of the rat pairs were implanted aseptically under isoflurane anesthesia with heart rate, temperature, and activity transponders (HR E-Mitter; Mini-Mitter, Bend, OR) in the abdomen at least 2 wk after their arrival and 2 wk before baseline data collection. The transponder was energized by an energizer/receiver device (ER4000; Mini-Mitter), and it transmitted heart rate, body temperature, and activity signals that in turn, were detected by the same device via telemetry. Heart rate, body temperature, and activity signals were sampled at 2 Hz and converted to heart rate (beats/min), temperature (°C), and activity counts, respectively, using custom software written in LabView 6.1 (National Instruments, Austin, TX). Converted heart rate and temperature data were averaged, and activity counts were summed up every 30 s; thus, a total of 2,880 data sets were collected daily.
When they were 1013 wk old, rats were housed individually in plastic cages (45 x 25 x 50 cm3) with Lignocel soft wood bedding on the bottom. The plastic cages were placed in two adjoining sound-attenuated recording rooms, one for the LS rat and the other for the LC rat, with a counterbalanced arrangement. Both rooms were illuminated by fluorescent lamps, and the location of each cage was adjusted to maintain the illuminance level at each cage bottom to be
300 lux when the fluorescent lamps were turned on. The lamps were connected to a power switch, under the control of a digital timer. Each room was also equipped with a dim red lamp (24 lux) so that routine measurement and cleaning could be performed when the fluorescent lamps were turned off. The two rooms were ventilated by a single air-conditioning system to maintain a similar environmental temperature and relative humidity at 2224°C and 5575%, respectively. Food pellets (3.25 kcal/g) and water were available ad libitum. Routine husbandry work was performed every 23 days to maintain the well-being of rats. All the animal facilities and care followed the guidelines provided by the Guide for the Care and Use of Laboratory Animals (National Academy Press, Washington, DC, 1996), and all procedures and experimental protocols were approved by the Institutional Animal Care and Use Committee.
Experimental design.
Baseline data collection started 1 wk after the rats were transferred to plastic cages. The experimental period for the LS rat included a 1-wk baseline period with lights on at 09002100, 13 wk of 12-h phase shifts in the LD cycle two times per week, and 10 days of recovery period with lights on at 09002100. LD shifts always involved a 24-h period of lights on (Fig. 1). The LC rats were maintained on the same lighting schedule with lights on at 09002100 throughout the experimental period except that lights-on periods were extended to 24 h every Monday during the LD shift period to maintain an equal amount of exposure to light for both the LC rats and the LS rats.

View larger version (19K):
[in this window]
[in a new window]
|
Fig. 1. Schematic representation of lighting schedule for experimental (LS) rats (A) and control (LC) rats (B). Blank horizontal rectangles indicate lights-on periods, and filled rectangles represent lights-off periods. The baseline period lasted at least 1 wk, the light-dark (LD) shift period 13 wk, and the recovery period 10 days. Open triangles indicate the time when routine husbandry work was performed.
|
|
Measurements for food intake and water intake were performed at around 2100 on Monday, Wednesday, and Friday for the LC rat throughout the experimental period. For the LS rat, measurements were made at the same time as the LC rat during baseline and recovery periods on Monday and Friday but at around 0900 on Wednesday during the LD shift period. That is, routine husbandry work was performed always during light-to-dark transitions or at the time corresponding to that on the previous day as the condition on Monday during LD shifts (Fig. 1). Wasted food pellets were searched and weighed, and the weight was added back to the weight of the food feeders. There was no evidence of food waste dependent on lighting schedule. Body weight was measured on the last day of the baseline period; every Monday of the 4th, 8th, and 12th wk of LD shifts; and the last day of recovery.
Cannulation and blood sampling.
Each rat was implanted aseptically under isoflurane anesthesia through the jugular vein with a polyurethane tubing (0.040 in. OD x 0.025 in. ID, MRE 040; Braintree Scientific) after 10 days of recovery. Later (2 days), beginning at 0900, 400 µl of blood were withdrawn every 3 h for 24 h. The blood sample was kept on ice for 3060 min. Serum samples were then taken by centrifugation (7,000 rpm, 10 min) and were frozen at 70°C until analysis. Triglyceride, total cholesterol, HDL-cholesterol, and LDL-cholesterol in the serum were analyzed by an autoanalyzer (Hitachi 7170).
Organ weight and examination.
After blood sampling (4 days), rats were killed under isoflurane. Heart, lung, liver, spleen, kidney, adrenal gland, and testis were removed and weighed soon after the rat stopped breathing for a few minutes. Routine microscopic examinations were performed on samples of the above-mentioned organs, aorta, stomach, and duodenum. Tissues were fixed in 10% formalin solution and, after being processed by an automatic dehydration machine (Shandon Pathcenter), were embedded in paraffin. Sections 3 µm thick were stained with hematoxylin and eosin and examined by our pathologist (J.-E. Tzeng).
Data analysis.
Daily body temperature and heart rate data were averaged for each hour accordingly, and circadian variations of these hourly mean data were analyzed using a 24-h cosine fitting model (1). Amplitudes of daily temperature and heart rate rhythm were averaged over weeks accordingly, to represent the mean amplitudes in baseline, successive weeks during LD shifts, and recovery. Circadian phase (acrophase) was defined as the time of the highest point of the daily fitted cosine curve.
Food intake and water intake data were summed up over three successive measurements and then divided by 7 to represent the daily mean values over a certain week. Daily mean food intake and water intake were then averaged across the weeks accordingly to represent mean values in the baseline, successive months during LD shifts, and recovery. Mean food and water intake during LD shifts and recovery was subtracted from baseline values and then divided by baseline values accordingly to represent food and water intake changes from baseline. Body weight data were subtracted by the baseline value or the value in the previous month to indicate successive body weight gain.
Two-factor mixed-design ANOVA with group (LS vs. LC) by time (baseline, 3 mo during LD shifts, and recovery) was performed on body weight, food intake, water intake, mean heart rate, mean temperature, and total activity data. Post hoc comparisons were performed by Tukey's test. A two-tailed independent t-test was performed to examine the difference between LS and LC rats in amplitude of circadian rhythms, body weight gain, and percent changes in food intake, water intake, mean heart rate, mean temperature, and total activity. A paired t-test or one-sample t-test was used to examine the differences from baseline across the experimental period. All statistical analyses were performed using SYSTAT 7.0 for Windows. An
-level of 0.05 was used for all statistical tests.
 |
RESULTS
|
---|
Changes of circadian rhythms during the LD shift period.
There were few qualitative differences between LS rats in daily rhythms of heart rate, body temperature, and activity throughout the experimental period. Thus the raster plot of temperature data is graphically represented in Fig. 2. The temperature rhythm of the LS rat responded to LD shifts by a mix of phase advance and delay (Fig. 2, BD). A gradual phase delay as the cluster of the temperatures above the daily mean moved backward was most prominent during the first 45 wk of LD shifts followed by intermittent phase delay and phase advance. The latter was noted as the cluster of the temperatures above the daily mean moved forward. Besides, the daily peaks and troughs of the hourly mean body temperature in the LS rat appeared mostly during the dark period and the light period, respectively (masking effects of LD), and most prominently during the later part of LD shifts (Fig. 2, BD). Changes of circadian heart rate and activity phase of the LS rat during LD shifts were similar to that of the temperature rhythm, as well as the masking effects of light and dark periods on heart rate and activity. Furthermore, the amplitude of circadian rhythms in the LS rat was reduced most of the time during the LD shifts (Fig. 3). Thus repeated 12-h LD shifts two times a week induced continual circadian desynchronization in F344 rats. After the return from repeated LD shifts, the LS rat reentrained to the regular LD cycle within 1 wk of the recovery period, with circadian phase back to baseline level and relatively faster than amplitudes. In contrast to the LS rat, the LC rat maintained a stable circadian phase and amplitude throughout the experimental period (Figs. 2A and 3).

View larger version (68K):
[in this window]
[in a new window]
|
Fig. 2. Examples of double-plotted body temperature in one LC rat (A) and three LS rats (BD) throughout the experimental period. Each data point represents a mean body temperature difference in 30 s from daily mean body temperature and is plotted only when it is larger than 0. The blank record lasting for 24 h in BD indicates recording failure on that day. Open and filled horizontal rectangles at the top of each plot represent the lights-on and lights-off periods, respectively, in baseline and recovery. Arrows represent the beginning and the end of the LD shift period, and vertical lines indicate the period when the schedule of the LD cycle was shifted to 180° opposite to that of the baseline.
|
|

View larger version (40K):
[in this window]
[in a new window]
|
Fig. 3. Mean amplitudes of daily body temperature (A) and heart rate (B) rhythm, analyzed by a 24-h cosine fitting model, throughout the experimental period (B, baseline; W, week in LD shifts; R, recovery) in LS and LC rats. Data are means ± SE. For body temperature rhythm, n = 5, except that missing data occurred in one LS rat in W6 because of temporary recording failure. For heart rate rhythm, n = 4, except that missing data occurred in one LS rat in W8 and in one LC rat in W4. Significant differences between LS and LC rats (*P < 0.05 and **P < 0.01, independent t-test). Significant differences from baseline (+P < 0.05 and ++P < 0.01, paired t-test). bpm, Beats/min.
|
|
Body weight, food intake, and water intake.
The LS rat had a greater body weight than the LC rat during LD shifts and still weighed more after 10 days of recovery in a regular LD cycle [group: F(1,14) = 5.3, P = 0.04; group x time: F(4,56) = 8.94, P < 0.001; Fig. 4]. Compared with the LC rat, the LS rat had increased body weight gain mainly in the 1st and 2nd mo of LD shifts (Fig. 4). Thus every LS rat gained more weight than its age-matched LC rat by the 3rd mo of LD shifts. Despite increased body weight and weight gain, the LS rat did not eat more than the LC rat throughout the experimental period (Fig. 5). However, relative to its own baseline level, the LS rat ate more in the 1st and 2nd mo of LD shifts and in recovery, whereas the LC rat ate less in the 1st mo of LD shifts. Thus mean percentage change in food intake was significantly higher in the LS rat in the 1st and 2nd mo of LD shifts and in recovery than in the LC rat. Similarly, the LS rat tended to drink more during LD shifts and in recovery relative to its own baseline level, but the value of the mean percentage change from baseline did not reach the level of statistical significance (Fig. 6).

View larger version (19K):
[in this window]
[in a new window]
|
Fig. 4. Mean body weight gain (y-axis on left and vertical bars on bottom) and mean body weight (y-axis on right and line graphs on top) throughout the experimental period (M, month) for LS-LC rat pairs. Data are means ± SE; n = 8. Significant differences between LS and LC rats (*P < 0.05 and **P < 0.01, independent t-test for body weight gain and Tukey's test for body weight).
|
|

View larger version (20K):
[in this window]
[in a new window]
|
Fig. 5. Mean food intake change from baseline (y-axis on left and lower vertical on bottom) and mean food intake (y-axis on right and line graphs on top) throughout the experimental period for LS-LC rat pairs. Data are means ± SE; n = 8. **Significant differences between LS and LC rats (P < 0.01, independent t-test). +Significant differences from 0 (P < 0.05, 1-sample t-test).
|
|

View larger version (20K):
[in this window]
[in a new window]
|
Fig. 6. Mean water intake change from baseline (y-axis on left and vertical bars on bottom) and mean water intake (y-axis on right and line graphs on top) throughout the experimental period for LS-LC rat pairs. Data are means ± SE; n = 8.
|
|
Heart rate, body temperature, and activity.
Both mean heart rate and mean body temperature in the LS and LC rats were maintained at baseline levels during LD shifts and in recovery. Conversely, both the LS and LC rats showed reduced total activity counts progressively over the experimental period (Fig. 7). The LS rat had a lower value of the mean percentage change of activity from baseline in the 2nd mo of LD shifts than that of the LC rat.

View larger version (19K):
[in this window]
[in a new window]
|
Fig. 7. Activity change from baseline (y-axis on left and vertical bars on bottom) and total activity (y-axis on right and line graphs on top) throughout the experimental period for LS-LC rat pairs. Data are means ± SE; n = 5. *Significant differences between LS and LC rats (P < 0.05, independent t-test). +,++ Significant differences from 0 (+P < 0.05 and ++P < 0.01, 1-sample t-test).
|
|
Organ weight and pathology.
The mean weights of heart, lung, liver, spleen, kidney, adrenal gland, and testis, as well as the ratios of organ weights to body weights, were not different for the LS and LC rats. No prominent pathological conditions and significant lipid infiltrations were found in any organ in either rat group.
Because of technical problems, only a few blood samples were collected. Thus the data of blood lipids were not reported.
 |
DISCUSSION
|
---|
This study demonstrates that repeated reversal of the external LD cycle two times per week resulted in continual phase shifts of circadian rhythms with reduced amplitudes and increased body weight gain in male F344 rats. To the best of our knowledge, this is the first experimental evidence vindicating the causal relationship of chronic circadian desynchronization and changes in body weight control in normal young rats. This finding corresponds to the results of epidemiological studies showing elevated weight gain (5) and prevalence of overweight (20) and of obesity (4, 8) in human shift workers.
A previous study applying weekly 12-h phase shifts in the LD cycle to female CD2F1 mice showed that the temperature rhythm of mice responded to each LD shift by a gradual phase delay and reentrained to the LD schedule by the 4th or 5th day (19). The wheel-running activity rhythm in cardiomyopathic male Syrian hamsters reentrains to a 12-h phase shift in the LD cycle by the 1st or 2nd day, with a phase delay or by the 4th or 5th day with a phase advance (cf., Fig. 2 in Ref. 22). In this study, a 12-h phase shift in the LD cycle was repeatedly applied to male F344 rats at twice-weekly intervals, and this treatment resulted in a mix of intermittent phase delay and advance; it was also intermingled with a masking effect of light and dark onset on activity, heart rate, and body temperature. However, the masking effect probably added little help to speed up reentrainment, since the amplitude of circadian rhythms was reduced even during the later period of LD shifts when the masking effect was most prominent, and it still took several days for the temperature rhythm to reentrain to the LD cycle in recovery (see Fig. 2, C and D). Thus twice-weekly 12-h shifts of the daily lighting schedule over months consistently resulted in continuous disruptions in circadian rhythmicity.
In contrast to previous findings of reduced body weight in female CD2F1 mice (19) and female Brown Norway rats (13, 14) subjected to weekly LD shifts, this study shows that the mean body weight and body weight gain in male F344 rats subjected to twice-weekly LD shifts were higher than in the LC rat. Compared with the LC rat, the LS rat maintained its mean body weight at a higher level across the 3 mo of LD shifts and even after 10 days of recovery in a regular LD cycle. However, the body weight gain was higher in the LS rat only for the first 2 mo of LD shifts. Increased weight gain was concomitant with increased food intake percentage relative to the baseline level in the LS rat, particularly in the first 2 mo of LD shifts and in recovery. Thus the tendency for the LS rat to gain more weight could result from an increase in energy intake. However, a decrease in energy output could also contribute to the increased weight gain in the LS rat. Relative to the baseline, the activity level in both the LS and LC rats was progressively reduced during LD shifts and in recovery. The decline of spontaneous activities could be age-related (16, 26). Nonetheless, the mean percentage change of activity in the LS rat was significantly lower than in the LC rat in the 2nd mo of LD shifts. An increase of energy intake concomitant with a decrease of energy output leads to the possibility of an elevated body weight set point that inevitably speeds up body weight gain. However, the treatment of repeated LD shifts at twice weekly intervals seemed not to increase body weight gain unlimitedly, since the mean weight gain in the LS rat was progressively reduced across the LD shift period and, in the last month, reached to the level similar to that of the LC rat. It was not known whether the gradual adaptation to LD shifts and/or the quantitative change of phase shift pattern during the later period of LD shifts, i.e., enhanced phase advance and masking effect, were causally related to the slow down of body weight gain in the LS rat.
A survey study in hospital staff members showed that workers who worked during the late (evening and night) shift reported a higher weight gain than the day-shift workers (5). There was a trend for the late-shift workers to report eating more and exercising less since beginning the late shift. Furthermore, it has been reported that prevalence of overweight is related to duration of work shift (20). The LS rat maintaining a greater body weight continuously during LD shifts and even in recovery appeared to display an effect similar to that of prolonged work shift on human subjects. In comparison with the results of previous studies in mice (19) and rats (13, 14), the present study seemed to provide a more appropriate animal model for human work shift, at least on the aspect of body weight control. Whether sex difference (female mice and rats in previous studies vs. male rats in the present study), strain difference (Brown Norway vs. albino F344 rats), and/or frequency difference in LD phase shifts are involved in the specific finding of this study will await future studies to clarify.
In summary, this study demonstrates that circadian desynchronization caused by repeated 12-h phase shifts of the LD cycle at twice-weekly intervals resulted in elevated body weight gain concomitant with increased food intake and reduced activity level in male F344 rats. These results suggest a causal relationship of chronic circadian desynchronization and changes in body weight control in male albino F344 rats.
 |
GRANTS
|
---|
This study was supported by the National Science Council, Republic of China, Grants NSC90-2413-H-194-019 and NSC91-2413-H-194-014.
 |
ACKNOWLEDGMENTS
|
---|
We are grateful to Wen-Yin Huang, Bessy Hung, Su-Fen Lai, Li-Chun Lin, Hau-Min Liu, Pei-Yu Ting, and Hui-Chun Wu for technical assistance.
 |
FOOTNOTES
|
---|
Address for reprint requests and other correspondence: L.-L. Tsai, Dept. of Psychology, National Chung-Cheng Univ., 168 University Road, Min-Hsiung, Chia-yi 621, Taiwan, R.O.C. (e-mail: psyllt{at}ccu.edu.tw)
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
 |
REFERENCES
|
---|
- Agren H, Koulu M, Saavedra JM, Potter WZ, and Linnoila M. Circadian covariation of norepinephrine and serotonin in the locus coeruleus and dorsal raphe nucleus in the rat. Brain Res 397: 353358, 1986.[CrossRef][ISI][Medline]
- Bøggild H and Knutsson A. Shift work, risk factors and cardiovascular disease. Scand J Work Environ Health 25: 8599, 1999.[ISI][Medline]
- Comperatore CA and Krueger GP. Circadian rhythm, desynchronosis, jet lag, shift lag, and coping strategies. Occup Med 5: 323341, 1990.[Medline]
- Di Lorenzo L, De Pergola G, Zocchetti C, L'Abbate N, Basso A, Pannacciulli N, Cignarelli M, Giorgino R, and Soleo L. Effect of shift work on body mass index: results of a study performed in 319 glucose-tolerant men working in a Southern Italian industry. Int J Obes Relat Metab Disord 27: 13531358, 2003.[CrossRef][Medline]
- Geliebter A, Gluck ME, Tanowitz M, Aronoff NJ, and Zammit GK. Work-shift period and weight change. Nutrition 16: 2729, 2000.[CrossRef][ISI][Medline]
- Ishizaki M, Morikawa Y, Nakagawa H, Honda R, Kawakami N, Haratani T, Kobayashi F, Araki S, and Yamada Y. The influence of work characteristics on body mass index and waist to hip ratio in Japanese employees. Ind Health 42: 4149, 2004.[ISI][Medline]
- Karlsson B, Knutsson A, and Lindahl B. Is there an association between shift work and having a metabolic syndrome? Results from a population based study of 27,485 people. Occup Environ Med 58: 747752, 2001.[Abstract/Free Full Text]
- Kawachi I, Colditz GA, Stampfer MJ, Willett WC, Manson JE, Speizer FE, and Hennekens CH. Prospective study of shift work and risk of coronary heart disease in women. Circulation 92: 31783182, 1995.[Abstract/Free Full Text]
- Knauth P and Rutenfranz J. Experimental shift work studies of permanent night, and rapidly rotating, shift systems. I. Circadian rhythm of body temperature and re-entrainment at shift change. Int Arch Occup Environ Health 37: 125137, 1976.[CrossRef][ISI][Medline]
- Knutsson A. Shift work and coronary heart disease. Scand J Soc Med Suppl 44: 136, 1989.[Medline]
- Knutsson A. Health disorders of shift workers. Occup Med 53: 103108, 2003.[Abstract/Free Full Text]
- Kort WJ and Weijma JM. Effect of chronic light-dark shift stress on the immune response of the rat. Physiol Behav 29: 10831087, 1982.[CrossRef][ISI][Medline]
- Kort WJ, Zondervan PE, Hulsman LO, Weijma IM, and Westbroek DL. Light-dark-shift stress, with special reference to spontaneous tumor incidence in female BN rats. J Natl Cancer Inst 76: 439446, 1986.[ISI][Medline]
- Machida K, Sugawara K, Kumae T, Shimaoka A, and Oshita Y. The effects of ethanol and sucrose on growth of Fischer rats and on results of their diagnostic test. J Japan Soc Nutr Food Sci 39: 369375, 1986.
- McCarter RJ and McGee JR. Transient reduction of metabolic rate by food restriction. Am J Physiol Endocrinol Metab 257: E175E179, 1989.[Abstract/Free Full Text]
- Monk TH. Shift work. In: Principles and Practice of Sleep Medicine, edited by Kryger MH, Roth T, and Dement WC. Philadelphia, PA: Saunders, 2002.
- Nakamura K, Shimai S, Kikuchi S, Tominaga K, Takahashi H, Tanaka M, Nakano S, Motohashi Y, Nakadaira H, and Yamamoto M. Shift work and risk factors for coronary heart disease in Japanese blue-collar workers: serum lipids and anthropometric characteristics. Occup Med 47: 142146, 1997.[Abstract]
- Nelson W and Halberg F. Schedule-shifts, circadian rhythms and lifespan of freely-feeding and meal-fed mice. Physiol Behav 38: 781788, 1986.[CrossRef][ISI][Medline]
- Niedhammer I, Lert F, and Marne MJ. Prevalence of overweight and weight gain in relation to night work in a nurses' cohort. Int J Obes Relat Metab Disord 20: 625633, 1996.[Medline]
- Parkes KR. Shift work and age as interactive predictors of body mass index among offshore workers. Scand J Work Environ Health 28: 6471, 2002.[ISI][Medline]
- Penev PD, Kolker DE, Zee PC, and Turek FW. Chronic circadian desynchronization decreases the survival of animals with cardiomyopathic heart disease. Am J Physiol Heart Circ Physiol 275: H2334H2337, 1998.[Abstract/Free Full Text]
- Rosmond R, Lapidus L, and Bjorntorp P. The influence of occupational and social factors on obesity and body fat distribution in middle-aged men. Int J Obes Relat Metab Disord 20: 599607, 1996.[Medline]
- Scott AJ and LaDou J. Shiftwork: effects on sleep and health with recommendations for medical surveillance and screening. Occup Med 5; 273299, 1990.[ISI][Medline]
- Siebenaler MJ and McGovern PM. Shiftwork: consequences and considerations. AAOHN J 39: 558567, 1991.[Medline]
- Suzuki K and Machida K. Effectiveness of lower-level voluntary exercise in disease prevention of mature rats. I. Cardiovascular risk factor modification. Eur J Appl Physiol 71: 240244, 1995.[CrossRef]
- Van Amelsvoort LG, Schouten EG, and Kok FJ. Duration of shiftwork related to body mass index and waist to hip ratio. Int J Obes Relat Metab Disord 23: 973978, 1999.[CrossRef][Medline]
Copyright © 2005 by the American Physiological Society.