Obesity in male volcano mice Neotomodon alstoni affects the daily rhythm of metabolism and thermoregulation.

The mouse N. alstoni spontaneously develops the condition of obesity in captivity when fed regular chow. We aim to study the differences in metabolic performance and thermoregulation between adult lean and obese male mice. The experimental approach included indirect calorimetry using metabolic cages for VO2 intake and VCO2 production. In contrast, the body temperature was measured and analyzed using intraperitoneal data loggers. It was correlated with the relative presence of UCP1 protein and its gene expression from interscapular adipose tissue (iBAT). We also explored in this tissue the relative presence of Tyrosine Hydroxylase (TH) protein, the rate-limiting enzyme for catecholamine biosynthesis present in iBAT. Results indicate that obese mice show a daily rhythm persists in estimated parameters but with differences in amplitude and profile. Obese mice presented lower body temperature, and a low caloric expenditure, together with lower VO2 intake and VCO2 than lean mice. Also, obese mice present a reduced thermoregulatory response after a cold pulse. Results are correlated with a low relative presence of TH and UCP1 protein. However, qPCR analysis of Ucp1 presents an increase in gene expression in iBAT. Histology showed a reduced amount of brown adipocytes in BAT. The aforementioned indicates that the daily rhythm in aerobic metabolism, thermoregulation, and body temperature control have reduced amplitude in obese mice Neotomodon alstoni.

Obese Neotomodon alstoni mice exhibit sexual dimorphism in the daily profile of circulating melatonin and clock proteins PER1 and BMAL1 in the hypothalamus and peripheral oscillators.

Obesity is a global health threat and a risk factor for several metabolic conditions. Though circadian dysfunction has been considered among the multiple causes of obesity, little work has been done to explore the relationship between obesity, circadian dysfunction, and sexual dimorphism. The Neotomodon alstoni mouse is a suitable model for such research. This study employed N. alstoni mice in a chronobiological analysis to determine whether there is circadian desynchronization of relative PER1 and BMAL1 protein levels in the hypothalamus, liver, visceral white adipose tissue, kidney, and heart. It also compared differences between sexes and lean and obese N. alstoni adult mice, by recording behavior and daily circulating serum melatonin as markers of circadian output. We found that obese mice display reduced locomotor activity. Additionally, Cosinor analyses of the relative expression of PER1 and BMAL1 show differences between lean and obese mice in a sex-linked manner. The PER1 24 h rhythm was absent in all tissues of obese males and significant in the tissues of obese females. The BMAL1 24 h rhythm also was significant in most of the tissues tested in lean males, whereas it was significant and shifted the acrophase (peak time of rhythm) in most of the tissues in obese females. Both lean male and female mice showed a rhythmic 24 h pattern of circulating serum melatonin. This daily profile was not only absent in obese mice of both sexes but showed sexual dimorphism. Obese male mice showed lower circulating levels of melatonin compared to lean male mice, but they were higher in obese females compared to lean females. Our results suggest that obesity in N. alstoni is associated with an internal circadian desynchronization in a sex-dependent manner. Overall, this study reinforces the need for further research on the neuroendocrinology of obesity and circadian rhythms using this biological model.

Daily cycle in hepatic lipid metabolism in obese mice, Neotomodon alstoni: Sex differences.

Disruption of circadian rhythms influences the pathogenesis of obesity, particularly with the basic regulation of food intake and metabolism. A link between metabolism and the circadian clock is the peroxisome proliferator-activated receptors (PPARs). The Neotomodon alstoni mouse, known as the "Mexican volcano mouse," may develop obesity if fed a normo-caloric diet. This manuscript documents the changes in part of the hepatic lipid homeostasis in both sexes of lean and obese N. alstoni mice, comparing the daily changes in the BMAL1 clock protein, in regulators of lipid metabolism (PGC-1α, PPARα-γ, SREBP-1c, and CPT-1α) and in free fatty acid (FFA) and hepatic triacylglyceride (TAG) metabolites in light-dark cycles. Hepatic tissue and blood were collected at 5, 10, 15, 19, and 24 h. Samples were analyzed by western blotting to determine the relative presence of protein. The results indicate that obesity affects daily changes in lipid metabolism and the BMAL1 profile in females considerably more than in males. These results suggest that the impact of obesity on lipid metabolism has important differences according to sex.

Neotomodon alstoni mice present sex differences between lean and obese in daily hypothalamic leptin signaling.

This article compared the effects of spontaneous obesity on the daily profile in the relative amount of the leptin receptor (LepRb), and its output. That is the precursor Pro-opiomelanocortin (POMC) over a 24-hour period and compared with differences in locomotion and food intake in periods of artificial light. Differences between lean and obese mice were examined, as were sex differences. Body weight, food intake and locomotor activity were monitored in freely moving lean and obese mice. Hypothalamic tissue was collected at 5 h, 10 h, 15 h, 19 h and 24 h. Samples were analyzed by western blotting to determine the relative presence of protein for LepRb, STAT3 phosphorylation (by pSTAT3/STAT3 ratio) and POMC. Obese mice were 60% less active in locomotion than lean mice during the night. While both locomotor activity and food intake were noticeably greater during the day in obese mice than in lean mice, the hypothalamus in obese mice showed a lower relative abundance of POMC and reduced pSTAT3/STAT3 ratio and leptin receptors. Behavioral and biochemical differences were more evident in obese females than in obese males. These results indicate that obesity in N. alstoni affects hypothalamic leptin signaling according to sex.

Differences in Photic Entrainment of Circadian Locomotor Activity Between Lean and Obese Volcano Mice (Neotomodon alstoni).

Obesity is a growing problem worldwide with a clear impact on health status. It is also a condition that negatively affects circadian rhythms. When the mouse Neotomodon alstoni is fed a regular rodent chow, some individuals develop obesity, representing an opportunity to compare the effects of spontaneous obesity upon the circadian organization in this species with that observed in other rodents with induced obesity. We report differences in the free running circadian locomotor activity rhythm and in the effects of light pulses between lean and obese mice. Also, the photo-induced expression of the c-Fos protein and vasoactive intestinal peptide (VIP) in the suprachiasmatic nucleus (SCN) were examined at circadian time (CT) 14 and 22. We show that obese mice have a larger dispersion of the period of circadian locomotor rhythm in constant darkness. Photic induced phase shifts are nearly 50% shorter at CT 14, and 50% larger at CT 22 than in lean mice. The photoinduction of VIP in the SCN at CT 22 was larger in obese mice, which may be related to the differences observed in photic phase shifting. Our work indicates that the obesity in Neotomodon has effects on the neural mechanisms that regulate the circadian system.

Hypothalamic expression of anorexigenic and orexigenic hormone receptors in obese females Neotomodon alstoni: effect of fasting.

Obesity is a world problem that requires a better understanding of its physiological and genetic basis, as well as the mechanisms by which the hypothalamus controls feeding behavior. The volcano mouse Neotomodon alstoni develops obesity in captivity when fed with regular chow diet, providing a novel model for the study of obesity. Females develop obesity more often than males; therefore, in this study, we analysed in females, in proestrous lean and obese, the differences in hypothalamus expression of receptors for leptin, ghrelin (growth hormone secretagogue receptor GHS-R), and VPAC, and correlates for plasma levels of total ghrelin. The main comparisons are between mice fed ad libitum and mice after 24 hours of fasting. Mice above 65 g body weight were considered obese, based on behavioral and physiological parameters such as food intake, plasma free fatty acids, and glucose tolerance. Hypothalamic tissue from obese and lean mice was analysed by western blot. Our results indicate that after ad libitum food access, obese mice show no significant differences in hypothalamic leptin receptors, but a significant increase of 60% in the GHS-R, and a nearly 62% decrease in VPAC2 was noted. After a 24-hour fast, plasma ghrelin increased nearly two fold in both lean and obese mice; increases of hypothalamic leptin receptors and GHS-R were also noted, while VPAC2 did not change significantly; levels of plasma free fatty acids were 50% less after fasting in obese than in lean animals. Our results indicate that in obese N. alstoni mice, the levels of orexigenic receptors in the hypothalamus correlate with overfeeding, and the fact that lean and obese females respond in different ways to a metabolic demand such as a 24-hour fast.

Evaluación de dieta purificada para la obtención de biomodelo de ratas anémicas / Evaluation of a purified diet to obtain a biomodel of anemic rats

Introducción: el desarrollo científico y tecnológico en las ciencias biológicas y biomédicas ha sido posible gracias a la utilización de modelos animales experimentales. La anemia por deficiencia de hierro (Fe), afecta aproximadamente a la tercera parte de la población mundial. La rata recién destetada ha sido el modelo animal más empleado en la obtención de un biomodelo experimental de anemia. Para la obtención de anemia se utiliza el método de depleción de la hemoglobina (Hb), mediante una alimentación basada en una dieta deficiente en Fe. Objetivo: el objetivo de este trabajo fue evaluar la eficacia de una dieta purificada a partir de caseína en la obtención de ratas anémicas. Métodos: se utilizaron 40 ratas Sprague Dawley recién destetadas (21-24 días), la mitad de cada sexo. Se alojaron en grupos de 3 del mismo sexo en cajas de acero inoxidable con piso de rejillas. Durante 8 semanas se les administró agua desionizada y una dieta de caseína al 12,58 por ciento de proteínas y 1,28 mgFe/Kg. Cada dos semanas se midió el peso corporal y a partir de la cuarta semana, la concentración de Hb. Resultados: se obtuvo un incremento significativo del peso corporal sin observarse diferencias entre hembras y machos. Se tomó como criterio de obtención de la anemia aquellos animales cuya Hb disminuyó al menos en un 30 por ciento del valor inicial promedio por grupo. El porcentaje de animales anémicos a las 8 semanas fue superior en las hembras (75 por ciento), mientras que en machos (60 por ciento). La dieta utilizada en este estudio permitió obtener ratas anémicas en el sexo hembras con una eficiencia aceptable, en relación al porcentaje de animales anémicos y al incremento del peso corporal. Conclusiones: la dieta utilizada en este estudio permitió obtener ratas anémicas en el sexo hembras con una eficiencia aceptable, en relación al porcentaje de animales anémicos y al incremento del peso corporal(AU)

Introduction: the scientific and technological development of biological and biomedical sciences has been possible due to the use of experimental animal models. Iron- (Fe-) deficiency anemia affects about one third of the world population. Just weaned rats have been the animal model most commonly used to obtain an experimental biomodel of anemia. The disease is obtained by the hemoglobin (Hb) depletion method, feeding the animal an iron-deficient diet. Objective: evaluate the efficacy of a purified diet based on casein to obtain anemic rats. Method: a study was conducted of 40 just weaned (21-24 days) Sprague Dawley rats, 20 of each sex. The animals were housed in groups of 3 rats of the same sex in stainless steel boxes with mesh bottoms. For 8 weeks the animals were administered deionized water and a casein diet of 12.58 percent protein and 1.28 mgFe/kg. Body weight was measured every two weeks. Hb concentration was gauged from the fourth week onwards. Results: a significant increase in body weight was obtained, with no differences between male and female rats. The criterion for anemia was at least a 30 percent decrease in Hb with respect to the average baseline value per group. The percentage of anemic animals at 8 weeks was higher for females (75 percent ) than for males (60 percent ) Conclusions: the diet used for the study made it possible to obtain female anemic rats with acceptable efficiency in relation to the percentage of anemic animals and the increase in body weight(AU)

Evaluación de dieta purificada para la obtención de biomodelo de ratas anémicas / Evaluation of a purified diet to obtain a biomodel of anemic rats

Introducción: el desarrollo científico y tecnológico en las ciencias biológicas y biomédicas ha sido posible gracias a la utilización de modelos animales experimentales. La anemia por deficiencia de hierro (Fe), afecta aproximadamente a la tercera parte de la población mundial. La rata recién destetada ha sido el modelo animal más empleado en la obtención de un biomodelo experimental de anemia. Para la obtención de anemia se utiliza el método de depleción de la hemoglobina (Hb), mediante una alimentación basada en una dieta deficiente en Fe. Objetivo: el objetivo de este trabajo fue evaluar la eficacia de una dieta purificada a partir de caseína en la obtención de ratas anémicas. Métodos: se utilizaron 40 ratas Sprague Dawley recién destetadas (21-24 días), la mitad de cada sexo. Se alojaron en grupos de 3 del mismo sexo en cajas de acero inoxidable con piso de rejillas. Durante 8 semanas se les administró agua desionizada y una dieta de caseína al 12,58 por ciento de proteínas y 1,28 mgFe/Kg. Cada dos semanas se midió el peso corporal y a partir de la cuarta semana, la concentración de Hb. Resultados: se obtuvo un incremento significativo del peso corporal sin observarse diferencias entre hembras y machos. Se tomó como criterio de obtención de la anemia aquellos animales cuya Hb disminuyó al menos en un 30 por ciento del valor inicial promedio por grupo. El porcentaje de animales anémicos a las 8 semanas fue superior en las hembras (75 por ciento), mientras que en machos (60 por ciento). La dieta utilizada en este estudio permitió obtener ratas anémicas en el sexo hembras con una eficiencia aceptable, en relación al porcentaje de animales anémicos y al incremento del peso corporal. Conclusiones: la dieta utilizada en este estudio permitió obtener ratas anémicas en el sexo hembras con una eficiencia aceptable, en relación al porcentaje de animales anémicos y al incremento del peso corporal

Introduction: the scientific and technological development of biological and biomedical sciences has been possible due to the use of experimental animal models. Iron- (Fe-) deficiency anemia affects about one third of the world population. Just weaned rats have been the animal model most commonly used to obtain an experimental biomodel of anemia. The disease is obtained by the hemoglobin (Hb) depletion method, feeding the animal an iron-deficient diet. Objective: evaluate the efficacy of a purified diet based on casein to obtain anemic rats. Method: a study was conducted of 40 just weaned (21-24 days) Sprague Dawley rats, 20 of each sex. The animals were housed in groups of 3 rats of the same sex in stainless steel boxes with mesh bottoms. For 8 weeks the animals were administered deionized water and a casein diet of 12.58 percent protein and 1.28 mgFe/kg. Body weight was measured every two weeks. Hb concentration was gauged from the fourth week onwards. Results: a significant increase in body weight was obtained, with no differences between male and female rats. The criterion for anemia was at least a 30 percent decrease in Hb with respect to the average baseline value per group. The percentage of anemic animals at 8 weeks was higher for females (75 percent ) than for males (60 percent ) Conclusions: the diet used for the study made it possible to obtain female anemic rats with acceptable efficiency in relation to the percentage of anemic animals and the increase in body weight

Obesity alters circadian behavior and metabolism in sex dependent manner in the volcano mouse Neotomodon alstoni.

The aim of the present study is to evaluate whether circadian locomotor activity, and the daily profile of plasma parameters related to metabolic syndrome (nutrients: glucose and triacylglycerides, and hormones: insulin and leptin), differ between male and female Neotomodon alstoni mice, both lean and obese. Young adult animals were captured in the field and kept at the laboratory animal facility. After 6 to 7 months feeding the animals ad libitum with a regular diet for laboratory rodents, 50-60% of mice became obese. Comparisons between sexes indicated that lean females were more active than males; however obese females reduced their nocturnal activity either in LD or DD, and advanced the phase of their activity-onset with respect to lights off. No differences in food intake between lean and obese mice, either during the day or night, were observed. Daily profiles of metabolic syndrome-related plasma parameters showed differences between sexes, and obesity was associated with increased values, especially leptin (500% in females and 273% in males) and insulin (150% in both females and males), as compared with lean mice. Our results indicate that lean mice display behavioral and endocrine differences between sexes, and obesity affects the parameters tested in a sex-dependent manner. The aforementioned leads us to propose N. alstoni, studied in captivity, could be an interesting model for the study of sex differences in the effects of obesity.