Hypothalamic expression of anorexigenic and orexigenic hormone receptors in obese femalesNeotomodon alstoni:Effect of fasting

Abstract

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.

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

“…Cells expressing c-Fos photoinduction in SCN were observed at both CT 14 and CT 22; a larger difference in some cells expressing c-Fos was noted in obese mice at CT 22 (Figure 3B). We previously found that photic phase shifts were shorter at CT 14 in obese mice ([42]; and the present work). However, we did not find an equivalent directional change in the photic induction at CT 14.…”

“…The possibility that a differential expression of VPAC2 receptors occurs in the SCN of obese Neotomodon should be tested. In a previous study, we observed differences in VPAC2 expression [42] as well as more unstable phase angle with the zeitgeber in obese Neotomodon [40]. In the present study, a larger dispersion of the free-running period was observed in obese animals, compared with a lengthening in period observed in obese mice fed with high-lipid diets [29].…”

“…Obesity in this model seems to be related to overfeeding during development, possibly due to an imbalance in the hypothalamus between orexigenic and anorexigenic endocrine signals such as leptin and ghrelin [42]. Our results indicate that obese N. alstoni mice show different changes in the photic response, reducing delays at CT 14 and increasing the advances at CT 22, which are different from those observed in other rodent models, such as mice fed high fat diet that present a decrease in the advance zone [23] or in the ob/ob mice in which phase shifts of locomotor activity are larger in the delay zone [26].…”

“…It is particularly useful to understand whether the altered mechanisms in obesity occur regardless of the model used, or if they are a consequence of the specific method used to induce obesity [38]. The endemic Mexican volcano mouse, Neotomodon alstoni, is an advantageous model for a variety of behavioral and physiological studies, including circadian rhythms and its relation to obesity [394041] and hypothalamic integration of food intake [42]. In this context, a mouse such as N. alstoni offers a different perspective, since some of these mice develop obesity with standard rodent diets, while others remain lean.…”

Melanin‐concentrating hormone peptidergic system: Comparative morphology between muroid species

“…Adult male Mexican volcano mice ( N alstoni , n = 5) were bred and raised in the animal facility of the Facultad de Ciencias, Universidad Nacional Autónoma de México, individually housed in a light‐ and temperature‐controlled environment (12 hr light/dark cycle, 23°C), and with free access to chow and water. Once animals reached 6 months of age, individuals identified as nonspontaneous obese (Báez‐Ruiz et al, ; Carmona‐Alcocer et al, ) were used in the remaining of the experiment. All handling of N alstoni animals followed the ethical guidelines of the National Research Council of the National Academy of Sciences Guide for the Care and Use of Laboratory Animals and the Official Mexican Standard NOM‐062‐Z00‐1999.…”