Diurnal and Infradian Rhythms in Lipid Parameters of Indian Catfish, Heteropneustes fossilis

Twentyfour-hour variation in ( 14 C) acetate incorporation in the liver lipid, and lipid concentrations in the liver and muscle tissues were studied during different phases of the annual reproductive cycle in the female freshwater catfish, H. fossilis . A 24-h rhythm in hepatic lipogenic activity was validated. Lipid concentration in liver and muscle also varied in a rhythmic fashion (t = 24 h). The mesor and amplitude of these rhythms appeared to be modulated by the phase of the annual gonadal cycle of H. fossilis . All three lipid parameters, in addition, exhibited low frequency rhythms with a t = 6 months or 3 months. The results indicate that the time of the day and month of the year for sampling in any experiment involving examination of lipid metabolism are of critical importance.     

Lipid changes in tissues from the cold-exposed,torpid and aroused pigmy mouse, Baiomys taylori

Brown fat, liver, heart and skeletal muscle tissue lipid, triglyeride, and protein have been quantitated during the pigmy mouse torpid cycle. Triglycerides appear to be the main tissue energy store for use of this organism throughout the cycle. Brown fat is depleted of its triglyceride from a control value of 3.48 mg per mg protein to 0.39 mg during torpor. There is a significant increase during arousal, 24 hr post-torpor. Data from liver extracts suggest a reverse trend. Skeletal muscle represents 24% of the mass of the mouse. The muscle triglycerides decrease to half that of the control and remain at that level until 24 hr post-torpor. No similarly significant trends are found in heart tissue. The total lipid levels of the tissues mirror the types of data already expressed for triglycerides. The decrease in muscle triglycerides may represent either endogenous utilization and/or the mobilization of these reserves to other organs such as the liver and brown fat.     

Daily and annual variations of the hepatic glucose 6-phosphate dehydrogenase activity and seasonal changes in the body fats of the gilthead seabream Sparus aurata

In mammalians, Glucose 6-phosphate dehydrogenase (G6PDH) is clearly related with the daily cycle lipogenesis/lipolysis and therefore with the photoperiod and activity. In fish the temporally changes on the activity of this enzyme have not been described. In this work, annual and diurnal activity of G6PDH was investigated in the liver of Sparus aurata in different seasonal conditions of temperature and photoperiod. During experiment the fish were kept in cages under natural temperature and photoperiod while consuming a commercial diet. The months studied were chosen to establish if there is any influence on the G6PDH activity, because of the change in temperature and photoperiod (equal photoperiod and different temperature, March and October; different photoperiod and equal temperature, May and November; and different photoperiod and temperature, June and January). To study the enzyme activity along the day, the livers of six fish were removed every 3 hr during 24 hr. Annual activity was determined as the average activity during 1 day. Also the annual changes on fat content in muscle and digestive system were studied. The Vmax (maximum velocity) showed seasonal changes in period and phase of the rhythms and for the Km (Michaelis-Menten constant) a period of 24 hr was found in all sampled months, except March, the phase time moves depending on the month. In addition, the annual variations in muscular fat and G6PDH-specific activity seem to be more related to the reproductive stage than any other variable considered.     

Diurnal Regulation of Lipid Metabolism and Applications of Circadian Lipidomics

The circadian timing system plays a key role in orchestrating lipid metabolism. In concert with the solar cycle, the circadian system ensures that daily rhythms in lipid absorption, storage, and transport are temporally coordinated with rest-activity and feeding cycles. At the cellular level, genes involved in lipid synthesis and fatty acid oxidation are rhythmically activated and repressed by core clock proteins in a tissue-specific manner. Consequently, loss of clock gene function or misalignment of circadian rhythms with feeding cycles （e.g., in shift work） results in impaired lipid homeostasis. Herein, we review recent progress in circadian rhythms research using lipidomics, i.e., large-scale profiling of lipid metabolites, to characterize circadian-regulated lipid pathways in mammals. In mice, novel regulatory circuits involved in fatty acid metabolism have been identified in adipose tissue, liver, and muscle. Extensive diversity in circadian regulation of plasma lipids has also been revealed in humans using lipidomics and other metabolomics approaches. In future studies, lipidomics platforms will be increasingly used to better understand the effects of genetic variation, shift work, food intake, and drugs on circadian-regulated lipid pathways and metabolic health.     

Role of photoperiodicity and circadian rhythm of glucocorticoids in synchronizing the fluctuations in free-radical oxidation of lipids in rats

A biphasic circadian rhythm in the content of liver lipid peroxidation products has been demonstrated in male Wistar rats housed under the conditions of 12L: 12D, with 3 hours of morning and evening twilight. Maxima of the concentration of the products were observed in the morning and early at night. The rhythm of lipid anti-oxidative activity was found in an anti-phase. Inversion of both the L: D cycle and glucocorticoid circadian rhythms (cortisol injections) led after 14-16 days to the same shifts in the rhythm of anti-oxidative activity. The data indicate that glucocorticoids modulate the diurnal rhythms of lipid anti-oxidative activity and may be responsible for the shifts in the rhythms of free radical oxidation, induced by inversion of the L: D cycle.     

Malondialdehyde content and circadian variations in brain, kidney, liver, and plasma of mice

In aerobic organisms, the use of oxygen (O(2)) to produce energy is associated with the production of Reactive Oxygen Species (ROS), which reacts with biological molecules to produce oxidized metabolites such as malondialdehyde (MDA). This experiment focused on male Swiss mice 12 weeks of age synchronized for 3 weeks by the 12 h light (rest)/12 h dark (activity) span. Different and comparable groups of animals (n=10) were sacrificed at six different circadian stages: 1, 5, 9, 13, 17, and 21 h after light onset (HALO). The 24 h mean MDA level varied among organs of mice in non-stress conditions and was comparable in brain and liver but lower than in kidney. As the MDA 24 h status constitutes only a part of ROS damages in sites differing by their oxygen use, lipid composition, and detoxification capacity, the temporal patterns of their MDA content were comparatively studied in relationship to the animal rest-activity cycle. The results revealed significant circadian rhythms with the peak time located during the rest span (approximately =5 HALO) for both brain and liver, but during the activity span for the kidney ( approximately =21 HALO) and plasma (approximately =13 HALO). This chronobiological study showed that under physiological conditions, lipid peroxidation depends on several factors. The MDA peak/trough might be used as a tool to detect moments of high/low sensitivity of tissues to ROS attack in rodents.     

Effect of dietary lipid level on fatty acid beta-oxidation and lipid composition in various tissues of haddock,Melanogrammus aeglefinus L

Haddock (Melanogrammus aeglefinus) is a gadoid fish species that deposits dietary lipid mainly in the liver. The fatty acid (FA) beta-oxidation activity of various tissues was evaluated in juvenile haddock fed graded levels of lipid. The catabolism of a radiolabelled FA, [1-(14)C]palmitoyl-CoA, through peroxisomal and mitochondrial beta-oxidation was determined in the liver, red and white muscle of juvenile haddock fed 12, 18 and 24% lipid in the diet. There was no significant increase in the mitochondrial or peroxisomal beta-oxidation activity in the tissues tested as the dietary lipid level increased from 12 to 24%. Peroxisomes accounted for 100% of the beta-oxidation observed in the liver, whereas mitochondrial beta-oxidation dominated in the red (91%) and white muscle (97%) of juvenile haddock. Of the tissues tested, red muscle possessed the highest specific activity for beta-oxidation expressed on a per mg protein or per g wet weight basis. However, white muscle, which forms over 50% of the body mass in gadoid fish was the most important tissue in juvenile haddock for overall FA catabolism. The total lipid and FA composition of these tissues were also determined. This study confirmed that the liver was the major lipid storage organ in haddock. The hepatosomatic index (HSI; 10.0-15.2%) and lipid (73.8-79.3% wet wt.) in the liver increased significantly as dietary lipid was increased from 12 to 24% lipid. There was no significant increase in the lipid composition of the white muscle (0.8% wet wt.), red muscle (1.9% wet wt.) or heart (2.5% wet wt.).     

Circadiane Uhren und Energiemetabolismus

Chrononutrition – circadian clocks and energy metabolism Genetically encoded endogenous clocks regulate 24‐hour rhythms of physiology and behavior. A central pacemaker residing in the suprachiasmatic nucleus synchronizes peripheral clocks found in all tissues with each other and with the external day‐night cycle. One function of circadian clocks is the regulation of energy metabolism via rhythmic activation of tissue‐specific clock‐controlled genes. In the liver, genes involved in glucose and lipid metabolism are regulated in this fashion, while in adipocytes, fatty acid release and adipokine secretion are controlled by the circadian clock. Disruption of circadian rhythms as seen, for example, in shift workers promotes the development of metabolic disorders such as obesity and type‐2 diabetes.     

Further demonstration of the ambient temperature dependence of the annual biological cycles in the edible dormouse,Glis glis

Summary In the male edible dormouse, it has been proposed that the annual temperature cycle is the major external factor triggering annual biological rhythms in this hibernating species. The present study was designed to explore (i) the effects of suppression of the annual thermoperiodic cycle under natural photoperiodic conditions, and (ii) the effects of acute exposure to a warm environment on basal plasma T4 levels observed during hibernation. The results of the first experiment demonstrate an absence of circannual cycles of hibernation, body weight, and endocrine thyroid and gonadal functions in the absence of annual fluctuations of temperature (constant warm environment at 24°C) despite the maintenance of a normal photoperiodic cycle. On the other hand, acute exposure to 24°C during the late stage of hibernation stimulated thyroid function as expressed by a consistent transitory rise in plasma T4 concentrations, which was maximal within 7 days and restored to basal levels after 14 days. These findings are in close agreement with the concept that in the edible dormouse, the annual thyroid cycle is synchronized with the annual temperature cycle. Moreover, the present study, combined with prior data indicating that the thyroid cycle induces the testis cycle, suggests that the ambient temperature cycle may be intricately involved in the control of neuroendocrine cycles in dormice, although the mechanism is still unknown.     

The 11-year cycle in human births

The annual numbers of human births were analyzed with regard to an 11-year cycle. The annual values were obtained from seven different regions: Australia, Germany, England and Wales, New Zealand, Japan, Switzerland, and the USA. Fifty-five annual values were obtained from each region for the years 1930 to 1984, comprising approximately five sunspot cycles. For each region the annual values were formed into 5 by 11 matrices; the eleven column means obtained were standardized, and plotted. A periodic regression technique, utilizing the fitting functions of the Fourier series, was used to evaluate the temporal order in the column means. Eleven-year rhythms were found and compared with solar and geophysical variables. Correlations were found with sunspots and solar flares, with terrestrial measures of magnetic disturbances (the magnetic indices derived from the K-index), and with temperature. The correlation of conceptions with the 11-year solar cycle may be a potential guide in the selection of further variables for the control and regulation of the rhythms in human conceptions.     

Aging-related oxidative stress depends on dietary lipid source in rat postmitotic tissues

We investigate mitochondrial-lipid peroxidation of mitotic (liver) and postmitotic (heart and skeletal muscle) tissues of rats fed lifelong on two different lipid sources: virgin olive oil (monounsaturated fatty acids) and sunflower oil (n–6 polyunsaturated fatty acids). Two groups of 80 rats each were fed over 24 months on a diet differing in the lipid source (virgin olive oil or sunflower oil). Twenty rats per group were killed at 6, 12, 18, and 24 months; liver, heart, and skeletal muscle mitochondria were isolated and the lipid profile, hydroperoxides, vitamin E, and ubiquinone as well as catalase activity measured. Lipid peroxidation was higher in postmitotic tissues, and sunflower oil led to a higher degree of polyunsaturation and peroxidation. The levels of -tocopherol adapted to oxidative stress and preferentially accumulated during aging in heart and skeletal muscle. In conclusion, the type of dietary fat should be considered in studies on aging, since oxidative stress is directly modulated by this factor. This study confirms that postmitotic tissues are more prone to oxidative stress during aging and proposes a hypothesis to explain this phenomenon.     

Seasonal fluctuation in lipid and cholesterol content of ovary, liver and blood serum in relation to annual sexual cycle in Heteropneustes fossilis (Bloch).

Seasonal fluctuation in lipid content of ovary and liver and cholesterol content of ovary, liver and serum in relation to annual reproductive cycle in H. fossilis has been worked out. Reduction in lipid content of liver was associated with decrease in hepatosomatic index (HSI) in prespawning and spawning phases. But there was an obvious increase in the lipid level of ovary in the above phases which coincided with enhanced gonadosomatic index (GSI) records. Serum and ovary showed a subsidence in their cholesterol contents in prespawning followed by increased level during spawning period. Substraction in liver cholesterol started in prespawning and continued till spawning phase and thereafter regained upward trend. Lipid and cholesterol levels in all organs studied along with GSI and HSI returned to initial values by the end of postspawning stage. Administration of clomid, sexovid, PGE1 and PGF2 alpha for a week did not induce any change in HSI, GSI, lipid and cholesterol values of liver and serum. However, these drugs were effective in suppressing the ovarian cholesterol within a week. The above drugs seem to affect cholesterol level indirectly since they trigger gonadotrophin secretion which in turn probably accelerated cholesterol utilization in ovary for increased steroid hormone output.     

Morphometric changes associated with the reproductive cycle and behaviour of the intertidal-nesting, male plainfin midshipman Porichthys notatus

Morphometric changes in body condition, liver, sonic muscle and gonadal development associated with the annual reproductive cycle and behaviour of the intertidal-nesting male plainfin midshipman Porichthys notatus were investigated. Body condition of type I males rapidly increased during the pre-nesting (PN) period, peaked at the beginning of the summer nesting cycle and then gradually declined to lowest levels during the non-reproductive (NR) period. The gonado-somatic index of type I males peaked during PN and then declined during the summer nesting cycle to lowest levels at the end of the nest cycle and during NR. Indices of sonic muscle and liver of type I males were lowest during NR, gradually increased during PN and then peaked during the summer nesting cycle. Results indicate that body condition and fecundity of type I males were positively correlated with body mass at the end of the nest cycle. These findings as they relate to the annual reproductive cycle and behaviour of the type I male P. notatus are discussed.     

Persistent twenty-four hour changes in liver and bone marrow despite suprachiasmatic nuclei ablation in mice

Rest-activity or cortisol rhythms can be altered in cancer patients, a condition that may impair the benefits from a timed delivery of anticancer treatments. In rodents, the circadian pattern in rest-activity is suppressed by the destruction of the suprachiasmatic nuclei (SCN) in the hypothalamus. We sought whether such ablation would result in a similar alteration of cellular rhythms known to be relevant for anticancer drug chronopharmacology. The SCN of 77 B6D2F(1) mice synchronized with 12 h of light and 12 h of darkness were destroyed by electrocoagulation [SCN(-)], while 34 animals were sham operated. Activity and body temperature were recorded by telemetry. Blood and organs were sampled at one of six circadian times for determinations of serum corticosterone concentration, blood leukocyte count, reduced glutathione (GSH), and dihydropyrimidine dehydrogenase (DPD) mRNA expression in liver and cell cycle phase distribution of bone marrow cells. Sham-operated mice displayed significant 24-h rhythms in rest-activity and body temperature, whereas such rhythms were found in none and in 15% of the SCN(-) mice, respectively. SCN lesions markedly altered the rhythmic patterns in serum corticosterone and liver GSH, which became nonsinusoidal. Liver DPD mRNA expression and bone marrow cell cycle phase distribution displayed similar 24-h sinusoidal patterns in sham-operated and SCN(-) mice. These results support the existence of another light-dark entrainable pacemaker that can coordinate cellular functions in peripheral organs. They suggest that the delivery of anticancer treatments at an optimal time of day may still be beneficial, despite suppressed rest-activity or cortisol rhythms.     

Sex-specific metabolic changes in the annual reproductive cycle of a freshwater catfish

Sex-specific enzymatic and other biochemical changes were studied in the annual reproductive cycle of the freshwater catfish, Clarias batrachus. Citrate synthase (CS) activity of brain, liver and skeletal muscle was maximum in spawning and minimum in postspawning showing a sharp decline in aerobic capacity after spawning. Similar CS activity in remaining phases of the annual reproductive cycle reflects similar energy need during regressed, preparatory and prespawning phases. Glucose 6-phosphate dehydrogenase (G6-PDH) activity declined in spawning and postspawning indicating a possible decrease in lipid and nucleic acid syntheses. The subsequent increase in G6-PDH activity with onset of resting and maintenance of the increased level throughout preparatory and prespawning phases shows restoration of biosynthetic activity. Higher activity of G6-PDH in female than male may be to satisfy a greater biosynthetic need of female reproduction and breeding. The decreased RNA content of tissues showed reduction in protein synthesis capacity during spawning and subsequent increase through postspawning until resting phase. The RNA content of brain and liver was higher in female than male during preparatory and prespawning, which may be associated with higher protein synthesis requirement of female for preparation of reproductive activities. The requirement based sex related changes in metabolism of catfish may be enzyme, tissue or reproductive phase-specific.     

Metformin affects the circadian clock and metabolic rhythms in a tissue-specific manner

Metformin is a commonly-used treatment for type 2 diabetes, whose mechanism of action has been linked, in part, to activation of AMP-activated protein kinase (AMPK). However, little is known regarding its effect on circadian rhythms. Our aim was to evaluate the effect of metformin administration on metabolism, locomotor activity and circadian rhythms. We tested the effect of metformin treatment in the liver and muscle of young lean, healthy mice, as obesity and diabetes disrupt circadian rhythms. Metformin led to increased leptin and decreased glucagon levels. The effect of metformin on liver and muscle metabolism was similar leading to AMPK activation either by liver kinase B1 (LKB1) and/or other kinases in the muscle. AMPK activation resulted in the inhibition of acetyl CoA carboxylase (ACC), the rate limiting enzyme in fatty acid synthesis. Metformin also led to the activation of liver casein kinase I α (CKIα) and muscle CKIε, known modulators of the positive loop of the circadian clock. This effect was mainly of phase advances in the liver and phase delays in the muscle in clock and metabolic genes and/or protein expression. In conclusion, our results demonstrate the differential effects of metformin in the liver and muscle and the critical role the circadian clock has in orchestrating metabolic processes.     

The inositol trisphosphate receptor regulates a 50-second behavioral rhythm in C. elegans.

The C. elegans defecation cycle is characterized by the contraction of three distinct sets of muscles every 50 s. Our data indicate that this cycle is regulated by periodic calcium release mediated by the inositol trisphosphate receptor (IP3 receptor). Mutations in the IP3 receptor slow down or eliminate the cycle, while overexpression speeds up the cycle. The IP3 receptor controls these periodic muscle contractions nonautonomously from the intestine. In the intestinal cells, calcium levels oscillate with the same period as the defecation cycle and peak calcium levels immediately precede the first muscle contraction. Mutations in the IP3 receptor slow or eliminate these calcium oscillations. Thus, the IP3 receptor is an essential component of the timekeeper for this cycle and represents a novel mechanism for the control of behavioral rhythms.     

Effects of dietary sea cucumber saponin on the gene expression rhythm involved in circadian clock and lipid metabolism in mice during nighttime-feeding

In mammals, clock rhythms exist not only in the suprachiasmatic nucleus, which is entrained by light/dark (LD) cycles, but also in most peripheral tissues. Recent studies have revealed that most physiology and behavior are subject to well-controlled daily oscillations; similarly, metabolic state influences the diurnal rhythm too. Previous studies have indicated that dietary sea cucumber saponin (SCS) could improve glucose and lipid metabolism of rodent. However, whether SCS could affect the expression of clock genes, which is involved in lipid metabolism, is unknown at present. The aim of this study is to investigate the effects of SCS on the clock and clock-controlled genes involved in lipid metabolism. ICR male mice were divided into a control and SCS group mice (add 0.03 % sea cucumber saponin to regular chow) and were fed at night (2030–0830 hours). After 2 weeks, clock genes expression in brain and liver, blood glucose, hormones, and lipid metabolic markers were analyzed. The results showed that dietary SCS caused alteration in rhythms and/or amplitudes of clock genes was more significant in brain than in liver. In addition, peroxisome proliferator-activated receptor (PPARα), sterol regulatory element binding protein-1c (SREBP-1c), together with their target genes carnitine palmitoyl transferase (CPT), and fatty acid synthase (FAS) showed marked changes in rhythm and/or amplitude in SCS group mice. These results suggested that SCS could affect the daily expression patterns of clock genes in brain and liver tissues, and alter the clock-controlled genes involved in lipid metabolism.