Glycogen and lipids are major storage forms of energy that are tightly regulated by hormones and metabolic signals. We demonstrate that feeding mice a high-fat diet (HFD) increases hepatic glycogen due to increased expression of the glycogenic scaffolding protein PTG/R5. PTG promoter activity was increased and glycogen levels were augmented in mice and cells after activation of the mechanistic target of rapamycin complex 1 (mTORC1) and its downstream target SREBP1. Deletion of the PTG gene in mice prevented HFD-induced hepatic glycogen accumulation. Of note, PTG deletion also blocked hepatic steatosis in HFD-fed mice and reduced the expression of numerous lipogenic genes. Additionally, PTG deletion reduced fasting glucose and insulin levels in obese mice while improving insulin sensitivity, a result of reduced hepatic glucose output. This metabolic crosstalk was due to decreased mTORC1 and SREBP activity in PTG knockout mice or knockdown cells, suggesting a positive feedback loop in which once accumulated, glycogen stimulates the mTORC1/SREBP1 pathway to shift energy storage to lipogenesis. Together, these data reveal a previously unappreciated broad role for glycogen in the control of energy homeostasis.
Daily observations on each of over one hundred individuals of C. lateralis by a special technique indicated that no animal remains continuously in the hibernating state longer than approximately 16 days (at an environmental temperature of 32° F). The arousals were more frequent at the beginning (i.e. in the autumn) and the ending (i.e. in the spring) of the whole hibernating period, than during the middle of this period (December and January). Adult males were found to arouse more frequently than did adult females or the juveniles of either sex. Preliminary data indicate that arousals are more frequent the higher the environmental temperature (up to 70–75° F), Observations on 12 C. columbianus, 9 C. tridecemlineatus, and 28 Glis glis indicated maximum continuous hibernation periods of 19, 12 and 33 days, respectively, at an environmental temperature of 32° F; C. richardsonii did not hibernate under our laboratory conditions.The trigger which starts each arousal is not known. Food and water intake during an arousal is not necessary, nor is defecation. Urination, however, takes place during every arousal. The observations strongly suggest that the urine voided was formed only while the animal was in the active homothermic state. It is suggested that it is the accumulation of metabolic end products which constitutes the stimulus for an arousal.
The state of torpidity (hibernation), the food consumption, and the weight of a number of C. lateralis were recorded daily, weekly, and weekly, respectively, for periods up to 2 years. At ambient temperatures of 32" F , 70' F , and 95-100' F and under constant lighting conditions, all animals displayed an approximately 1-year cyclic variation in weight which roughly paralleled the consumption of food. Under these constant conditions of light and temperature the animals subjected to 32O F and 70" F hibernated, i.e., their body temperature dropped nearly to the ambient and they became torpid. The body temperature of animals kept a t 95-100' F could not drop and these animals did not become torpid.Hibernation could not be induced by removal of food but was greatly prolonged if food was not present in the cages a t the time the whole hibernation period was ending. The onset of hibernation could be changed only slightly by changing the day lengths. Hibernation was possible only a t a specific stage of the weight cycle. The length of the weight cycle was shortened by exposure to an ambient temperature of 95-100" F. By manipulation of the length of the exposure to the high temperature it was possible to have animals hibernating in summer and active in winter. I t was not possible to produce a similar shift in the phase of the weight cycle, and hence of hibernation, by changing the lighting conditions.
Background: TORC1 is an evolutionarily conserved nutrient-sensitive protein kinase localized on late endosomal compartments. Results: Rab5 is an essential regulator of TORC1 activity in yeast and mammalian cells, through its role in regulating PI(3)P synthesis. Conclusion: Rab5 and PI(3)P are evolutionarily conserved regulators of TORC1. Significance: New insights into the complexity of mTORC1 signaling are presented.
FOUR ElQURESThe seal has peculiar respiratory habits for a mammal. While seals do not submerge for long periods they nevertheless breathe intermittently whenever they are active. Even
The selected temperature of two- to three-inch trout (Salvelinus fontinalis, Mitchill) was determined in a horizontal gradient a number of times during the months of November, December, January, February and March. The data, which were collected over four years, indicated that during the early part of winter (November, December and January), there was a fall of the selected temperature which paralleled in a general way a gradual fall of the acclimation temperature. The consistency of this parallelism was so poor, however, as to suggest that at least part of the change in selected temperature was relatively independent of the change in acclimation temperature. During the later part of the winter (February and March) there was a rise of the selected temperature which occurred regularly, regardless of whether the acclimation temperature rose, fell or remained constant. It is concluded that there was, for these animals, a seasonal change of the selected temperature which was distinct from the changes in selected temperature brought about by changes of the acclimation temperature.
The duration of the hibernation season of 13-lined ground squirrels, Citellus tridecemlineatus, repeatedly aroused over the winter, was only slightly less than that of undisturbed animals. The aroused animals ate more than eight times as much food during the middle of their hibernation season. This suggests that ground squirrels compensate by increased food intake for extra energy expenditure forced on them by repeated arousals. Aroused animals deprived of food lost weight at a greater rate than undisturbed animals. When food was returned they gained weight rapidly. However, weights did not return to predeprivation levels, but only to levels appropriate for the stage of the cycle at the time food was returned. These findings suggest that, even when ground squirrels are losing weight over the winter, they regulate their weight, but at a level that progressively declines. The underlying mechanisms probably depend on adjustments to the balance between medial and lateral hypothalamic areas.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.