RESUMEN
Many daily cycles are imposed on us by our environment, such as alternating days and nights, temperature fluctuations or rhythms in food availability. When food is accessible every day at the same time, animals will adapt their physiology and behaviour to match the daily meal. They will anticipate the access to food by waking up and being active in the hours prior to feeding, foraging for food. Adaptation of physiology to changing conditions of food availability is not only evident at the behavioural level, but also for hormonal systems. Thus, corticosteroids, melatonin, leptin/ghrelin, insulin/glucagon, orexins and thyroid hormones, which show rhythmic profiles of secretion in ad libitum feeding conditions, are sensitive to increase and/or depletion in energy supplies and will be influenced when food sources are limited or available at unusual times. The present review reports the influence of restricted feeding schedules on secretion profiles of diverse hormones compared to normal ad libitum feeding conditions in rodents. In the end, the interplay between these systems and their response to environmental challenges will allow the animal to maintain their fitness for survival.
Asunto(s)
Conducta Alimentaria , Hormonas/metabolismo , AnimalesRESUMEN
Restricted feeding schedules (RFS) entrain digestive, hormonal, and metabolic functions as well as oscillations of clock genes, such as Per1 and Per2, in peripheral organs. In the brain, in particular the hypothalamus, RFS induce and shift daily rhythms of Per1 and Per2 expression. To determine whether RFS affect clock genes in extra-SCN oscillators in a uniform manner, the present study investigated daily rhythms of Per1, Per2, and Bmal1 expression in various hypothalamic regions. Wistar rats were entrained to daily RFS (2 h food access starting at ZT6, RFS) or fed ad libitum (C) for three weeks. Brains were sampled every 3 h starting at ZT0, and were processed with in situ hybridization. In response to RFS, Per1 expression showed a 3 h phase advance in the suprachiasmatic nucleus (SCN), while Per2 and Bmal1 remained unaffected. Per1 was triggered at ZT6, anticipating food access in both arcuate (ARC) and dorsomedial nuclei (DMH), and was unaffected in the ventromedial (VMH) and paraventricular (PVN) nuclei. In contrast, Per2 expression during RFS showed a marked postprandial peak in the PVN, was unchanged in the ARC, and was down-regulated in the DMH and VMH. The temporal patterns of Bmal1 expression were not significantly modified in RFS rats. RFS differentially affected clock-gene expression (phase change, up- or downregulation) depending on the combination of hypothalamic nuclei and targeted genes. Present data highlight that metabolic or temporal cues elicited by feeding modify the temporal organization in the hypothalamus and are not exclusive for a food-entrained oscillator.
Asunto(s)
Alimentación Animal , Regulación de la Expresión Génica , Hipotálamo/metabolismo , Transactivadores/genética , Animales , Relojes Biológicos , Proteínas CLOCK , Privación de Alimentos , Hibridación in Situ , Masculino , Modelos Biológicos , Oscilometría/métodos , Ratas , Ratas Wistar , Factores de Tiempo , Transactivadores/biosíntesisRESUMEN
Food-anticipatory activity that animals express before a daily timed meal is considered as the behavioral output of a feeding-entrainable oscillator whose functional neuroanatomy is still unknown. In order to identify the possible brain areas involved in that timing mechanism, we investigated local cerebral metabolic rate for glucose during food-anticipatory activity produced either by a 4-h daily access to food starting 4 h after light onset or by a hypocaloric feeding provided at the same time. Local cerebral metabolic rate for glucose measured by the labeled 2-[(14)C]-deoxyglucose technique was quantified in 40 structures. In both groups of food-restricted rats, three brain regions (the nucleus of the solitary tract, the cerebellar cortex and the medial preoptic area) showed a decrease in local cerebral metabolic rate for glucose, compared with control ad libitum animals. In addition, only one structure, the paraventricular thalamic nucleus, was affected by temporal restricted feeding, and not by hypocaloric feeding, compared with ad libitum rats. By contrast, three brain regions, i.e. the intergeniculate leaflets, the paraventricular hypothalamic and the arcuate nuclei, showed specifically metabolic decreases during anticipation of hypocaloric feeding, and not during anticipation of temporal restricted feeding, compared with the ad libitum group. Expression of food-anticipatory activity appears to be regulated by an integrated neural circuit of brainstem and hypothalamic pathways, with hypocaloric feeding involving more extensive forebrain areas than temporal restricted feeding.
Asunto(s)
Corteza Cerebral/metabolismo , Ritmo Circadiano/fisiología , Conducta Alimentaria/fisiología , Glucosa/metabolismo , Actividad Motora/fisiología , Animales , Antimetabolitos/farmacología , Conducta Animal , Índice de Masa Corporal , Corteza Cerebral/efectos de los fármacos , Desoxiglucosa/farmacología , Ayuno/fisiología , Conducta Alimentaria/efectos de los fármacos , Masculino , Actividad Motora/efectos de los fármacos , Ratas , Ratas Long-Evans , Factores de TiempoRESUMEN
Parenteral magnesium loading test has been proposed as an adequate mean to evaluate magnesium status. However, applied tests vary among different laboratories and standardized procedure is not available. In the present study, we assessed magnesium status in 32 healthy adult French subjects by magnesium loading test using MgCl2 and determination of magnesium concentrations in plasma and erythrocytes. We observed a positive correlation between plasma and erythrocyte magnesium concentrations, but there was no correlation between magnesium retention and basal urinary excretion of magnesium, and plasma or erythrocyte magnesium concentrations.
Asunto(s)
Deficiencia de Magnesio/diagnóstico , Magnesio/administración & dosificación , Adulto , Anciano , Femenino , Humanos , Infusiones Intravenosas , Magnesio/sangre , Magnesio/normas , Magnesio/orina , Cloruro de Magnesio/administración & dosificación , Cloruro de Magnesio/normas , Deficiencia de Magnesio/sangre , Deficiencia de Magnesio/orina , Masculino , Persona de Mediana Edad , Valores de ReferenciaRESUMEN
Plasmapheresis and low-density lipoprotein (LDL)-apheresis are recognized procedures for the treatment of hyperlipidemia resistant to diet and lipid-lowering drugs and provide information on cholesterol synthesis in hypercholesterolemic patients. However, cholesterol synthesis after acute cholesterol removal from plasma has never been investigated in normocholesterolemic patients. In this study, cholesterol synthesis was evaluated in three normocholesterolemic patients by determination of plasma lathosterol, lathosterol-to-cholesterol ratio, and plasma mevalonic acid. In a short-term kinetic study, samples were collected before and after plasmapheresis and every 6 hours during 24 hours. In the second part of the study, cholesterol synthesis was evaluated daily for 3 days. In normocholesterolemic patients, cholesterol returns to basal levels in 3 days. However, cholesterol removal did not result in a significant increase in lathosterol-to-cholesterol ratio or in plasma mevalonic acid, despite a slight increase in lathosterol. In contrast, when repeated plasma exchanges induced a dramatic hypocholesterolemia (< 1 mmol/liter), an acute but transient stimulation of cholesterol synthesis was observed (lathosterol/cholesterol ratio and MVA, respectively, increase from 8.2 to 22.3 and from 28 nmol/liter to 98 nmol/liter). This study shows that cholesterol synthesis is not stimulated by plasmapheresis in normocholesterolemic patients but is enhanced in dramatic hypocholesterolemic patients (< 1 mmol/liter).
Asunto(s)
Colesterol/biosíntesis , Plasmaféresis , Colesterol/sangre , Femenino , Humanos , Masculino , Ácido Mevalónico/sangre , Persona de Mediana EdadRESUMEN
The effects of simvastatin and pravastatin on cholesterol biosynthesis were compared in 26 hypercholesterolemic patients who were randomly allocated to either simvastatin or pravastatin treatment (20 mg once daily) for 6 weeks in a crossover trial. Serum total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) lathosterol (latho) concentrations and lathosterol/cholesterol (latho/chol) ratios (the latter two are considered as reliable indices of whole body cholesterol synthesis) were evaluated at the beginning and end of each therapeutic sequence. Reductions in TC and LDL-C were more pronounced (P < 0.001) with simvastatin (TC = -28.0%, LDL-C = -35.6%) than with pravastatin (TC = -19.6%, LDL-C = -25.2%). These results were associated with concomitant decreases in both latho concentrations (-59.0% with simvastatin and -37.0% with pravastatin) and latho/chol ratios (-43.0% with simvastatin and -20.3% with pravastatin). Simvastatin resulted in more marked diminutions of latho concentrations (P < 0.01) and latho/chol ratios (P < 0.05) than pravastatin. These results suggest that the better efficacy of simvastatin on serum cholesterol and LDL cholesterol might result in part from a greater inhibitory action of simvastatin on cholesterol synthesis compared with that of pravastatin.
Asunto(s)
Anticolesterolemiantes/farmacología , Colesterol/biosíntesis , Inhibidores Enzimáticos/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Hiperlipoproteinemia Tipo II/tratamiento farmacológico , Lovastatina/análogos & derivados , Pravastatina/farmacología , Adolescente , Adulto , Anciano , Anticolesterolemiantes/uso terapéutico , Apolipoproteínas/sangre , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Estudios Cruzados , Método Doble Ciego , Inhibidores Enzimáticos/uso terapéutico , Femenino , Humanos , Hiperlipoproteinemia Tipo II/metabolismo , Hígado/efectos de los fármacos , Hígado/enzimología , Lovastatina/farmacología , Lovastatina/uso terapéutico , Masculino , Ácido Mevalónico/metabolismo , Persona de Mediana Edad , Pravastatina/uso terapéutico , Simvastatina , Resultado del Tratamiento , Triglicéridos/sangreRESUMEN
To gain further insight into the effects of insulin on cholesterol synthesis in humans, 19 newly insulin-treated diabetic patients were studied before any insulin treatment (study day 1) and after a few days of optimized glycemic control with a continuous intravenous insulin infusion (study day 2). The patients were divided into two groups according to their clinical characteristics and laboratory disorders. Groups I and II consisted, respectively, of 10 newly diagnosed type I diabetic patients and nine type II diabetic patients with secondary failure to oral antidiabetic drugs. Cholesterol synthesis was estimated from the determination of serum lathosterol, a metabolic precursor in the cholesterol pathway, and from the serum lathosterol to cholesterol ratio. Serum cholesterol (millimolar, mean +/- SEM) remained unchanged in both groups. After insulin therapy (study day 2), serum lathosterol (micromolar) and the serum lathosterol to cholesterol ratio (molar ratio x 10(3)) were significantly increased as compared with baseline (study day 1). Serum lathosterol levels were as follows: 9.9 +/- 2.0 versus 4.1 +/- 0.4 (P < .02) in group I, and 9.9 +/- 0.8 versus 5.7 +/- 0.7 (P < .005) in group II; serum lathosterol to cholesterol ratios were 2.10 +/- 0.39 versus 0.86 +/- 0.11 (P < .005) in group I, and 1.92 +/- 0.12 versus 0.98 +/- 0.10 (P < .001) in group II. The data indicate that in newly insulin-treated diabetic patients, short-term intensive insulin therapy has a stimulatory effect on cholesterol synthesis and even results in cholesterol overproduction.