To eat or not to eat: the effect of AICAR on food intake regulation in yellow-bellied marmots (Marmota flaviventris)

Abstract

SUMMARYMammals that hibernate (hibernators) exhibit a circannual rhythm of food intake and body mass. In the laboratory during the winter hibernation period, many hibernators enter a series of multi-day torpor bouts, dropping their body temperature to near ambient, and cease to feed even if food is present in their cage. The mechanism(s) that regulates food intake in hibernators is unclear. Recently, AMP-activated protein kinase (AMPK) has been shown to play a key role in the central regulation of food intake in mammals. We hypothesized that infusing an AMPK activator, 5-aminoimidazole-4-carboxamide 1 B-D-ribofuranoside (AICAR), intracerebroventricularly (ICV) into the third ventricle of the hypothalamus would stimulate yellow-bellied marmots (Marmota flaviventris) to feed during their hibernation season. Infusion of AICAR ICV into marmots at an ambient temperature of 22°C caused a significant (P<0.05) increase in food intake. In addition, animals stimulated to feed did not enter torpor during the infusion period. Marmots ICV infused with saline did not increase food intake and these animals continued to undergo torpor at an ambient temperature of 22°C. Our results suggest that AICAR stimulated the food intake pathway, presumably by activating AMPK. These results support the hypothesis that AMPK may be involved in regulating food intake in hibernators and that there may be common neural pathways involved in regulating feeding and eliciting torpor.

Post-Stroke Hypothermia Provides Neuroprotection through Inhibition of AMP-Activated Protein Kinase

“…The tissue type, animal species, and duration and depth of hypothermia may contribute to these differences. Interestingly, administration of the somewhat non-selective AMPK activator AICAR into hibernating marmots led to a significant increase in food intake and failure to enter torpor (Florant et al, 2010), suggesting that AMPK may play a role in the metabolic downregulation seen in hibernating species (Drew et al, 2007). A dramatic reduction in pAMPK occurred in stroke mice after hypothermia in our experimental setting.…”

Cholecystokinin activation of central satiety centers changes seasonally in a mammalian hibernator

“…Thus, the decline in the number of Fos-positive neurons over the active season may result from increased fattening and leptin resistance. Appetite regulation in mammals is a highly complex process, making it likely that other mechanisms contribute to satiation in hibernating species including action of the gut hormones ghrelin and peptide YY, insulin, neuropeptide Y, and hypothalamic AMP kinase [6,8,16,17,19,20,23]. …”

AMPK and ACCchange with fasting and physiological condition in euthermic and hibernating golden-mantled ground squirrels (Callospermophilus lateralis)

“…Information on how AMPK acts in specific areas of the brain, such as hypothalamus, where AMPK acts as a fuel sensor, is lacking in the hibernation literature. Recent experiments by Florant et al (2010) demonstrated that central infusion of the AMPK agonist 5-aminoimidazole-4-carboxamide 1 B-D-ribofuranoside (AICAR) into the third ventricle of winter aphagic marmots caused an initiation of food intake, consistent with AMPK’s role in increasing food intake.…”