ABSTRACT
Growth and differentiation are reduced or stopped during hibernation, an energy conserving strategy in harsh seasons by lowered metabolism and body temperature. However, few studies evaluated this in a same individual using a non-invasive method. In this study, we applied a non-invasive tracking method of the nail growth throughout the hibernation period in the same hibernating animals, the Syrian hamster (Mesocricetus auratus). We found that nail growth was markedly suppressed during the hibernation period but rapidly recovered by the exit from the hibernation period. Our data suggest that nail growth was arrested during deep torpor, a hypometabolic and hypothermic state, but recovered during periodic arousal, a euthermic phase. Consistent with this, nail stem cells located in the nail matrix did not exit the cell cycle in the deep torpor. Thus, hibernation stops nail growth in a body temperature-dependent manner.
Subject(s)
Hibernation , Animals , Hibernation/physiology , Mesocricetus , Nails/physiology , Body Temperature/physiology , Male , Cricetinae , Torpor/physiology , Cold TemperatureABSTRACT
OBJECTIVE: The regulation of food intake is a major research area in the study of obesity, which plays a key role in the development of metabolic syndrome. Gene targeting studies have clarified the roles of hypothalamic neurons in feeding behavior, but the deletion of a gene has a long-term effect on neurophysiology. Our understanding of short-term changes such as appetite under physiological conditions is therefore still limited. METHODS: Targeted recombination in active populations (TRAP) is a newly developed method for labeling active neurons by using tamoxifen-inducible Cre recombination controlled by the promoter of activity-regulated cytoskeleton-associated protein (Arc/Arg3.1), a member of immediate early genes. Transgenic mice for TRAP were fasted overnight, re-fed with normal diet, and injected with 4-hydroxytamoxifen 1 h after the refeeding to label the active neurons. The role of labeled neurons was examined by expressing excitatory or inhibitory designer receptors exclusively activated by designer drugs (DREADDs). The labeled neurons were extracted and RNA sequencing was performed to identify genes that are specifically expressed in these neurons. RESULTS: Fasting-refeeding activated and labeled neurons in the compact part of the dorsomedial hypothalamus (DMH) that project to the paraventricular hypothalamic nucleus. Chemogenetic activation of the labeled DMH neurons decreased food intake and developed place preference, an indicator of positive valence. Chemogenetic activation or inhibition of these neurons had no influence on the whole-body glucose metabolism. The labeled DMH neurons expressed prodynorphin (pdyn), gastrin-releasing peptide (GRP), cholecystokinin (CCK), and thyrotropin-releasing hormone receptor (Trhr) genes. CONCLUSIONS: We identified a novel cell type of DMH neurons that can inhibit food intake and promote feeding-induced positive valence. Our study provides insight into the role of DMH and its molecular mechanism in the regulation of appetite and emotion.
Subject(s)
Dorsomedial Hypothalamic Nucleus/metabolism , Eating , Neurons/metabolism , Animals , Cholecystokinin/genetics , Enkephalins/genetics , Feeding Behavior , Male , Mice , Mice, Transgenic , Protein Precursors/geneticsABSTRACT
The hypothalamus plays a central role in monitoring and regulating systemic glucose metabolism. The brain is enriched with phospholipids containing poly-unsaturated fatty acids, which are biologically active in physiological regulation. Here, we show that intraperitoneal glucose injection induces changes in hypothalamic distribution and amounts of phospholipids, especially arachidonic-acid-containing phospholipids, that are then metabolized to produce prostaglandins. Knockdown of cytosolic phospholipase A2 (cPLA2), a key enzyme for generating arachidonic acid from phospholipids, in the hypothalamic ventromedial nucleus (VMH), lowers insulin sensitivity in muscles during regular chow diet (RCD) feeding. Conversely, the down-regulation of glucose metabolism by high fat diet (HFD) feeding is improved by knockdown of cPLA2 in the VMH through changing hepatic insulin sensitivity and hypothalamic inflammation. Our data suggest that cPLA2-mediated hypothalamic phospholipid metabolism is critical for controlling systemic glucose metabolism during RCD, while continuous activation of the same pathway to produce prostaglandins during HFD deteriorates glucose metabolism.