Obesity is a life threatening disease with economically devastating consequences. Food intake (FI) reduction is the cornerstone for obesity treatment and has largely been unsuccessful. We offer an alternative approach- reducing food hoarding (FH) that thereby decreases stored foods thus decreasing the opportunities and increasing the efforts required to overeat. Most animals, including humans, hoard food. FH has morphed from a strategy to combat food scarcity into excessive external energy storage due to abundant, inexpensive, calorically-dense food, larger food storage units and improved food shelf lives - factors we believe significantly contribute to the human obesity increases. The most potent stimulator of FH is hunger exacerbating 'normal'food purchases by humans or foraged/hoarded food by rodents. Moreover, because ~85% of FI occurs at home and because obese store more calories per person than their lean counterparts, it is even easier for the obese to overeat. It's not surprising that a common recommendation for weight loss is reducing food stored at home. The innovation of this proposal lies with: 1) study of an unappreciated behavior --FH, 2) the novel animal model of human FH -- Siberian hamsters, a laboratory model that mimics FH in nature, 3) our unique housing system where hamsters earn food pellets to eat and hoard by wheel running, and 4) several approaches: fluorescent in situ hybridization, an unique inhibitor of ghrelin activation (GO-CoA-Tat) and tests of the role of brai peroxisome proliferator- activated receptor gamma (PPAR?) in FH. We hypothesize that a FH network is stimulated by FD causing increases in ghrelin secretion. Ghrelin stimulates neurons bearing ghrelin receptors [growth hormone secretagogue (GHSR)]. These include arcuate nucleus (Arc) AgRP/gamma-amino butyric acid (GABA) neurons and ventral tegmental area (VTA) dopamine (DA) neurons. Stimulation of their GHSRs increases PPAR? found therein. Finally, Arc AgRP neurons release AgRP at several terminal sites and GABA from their projections to the lateral parabrachial nucleus (LPBN) collectively stimulating FH. Our overarching hypothesis is that FD engages a distributed FH network with the hunger-released stomach peptide ghrelin a key initiator that interacts with several central sites and neurochemicals traditionally designated as controllers of FI and reward, as well as a virtually unexplored central factor, PPAR?. We will test this hypothesis in two Specific Aims 1: How does ghrelin initiate the persisting stimulation of FH? and What is role of AgRP neurons and brain PPAR? in the persisting increases in FH? Collectively, we will identify key components driving the prolonged FH increases deepening our understanding of this fundamental ingestive behavior of humans and rodents that we almost exclusively study. This will greatly impact behavioral or drug therapies for obesity and for the genetic disorder Prader-Willi-Syndrome characterized by obesity and uncontrollable FH.
Current approaches to the obesity problem have focused on the control of food intake and have been largely unsuccessful. Food, however, also has to be acquired (foraged) and usually is stored for subsequent consumption (hoarded) in refrigerators, freezers, pantries. The hormonal and especially brain control of foraging and hoarding in any species is virtually unknown and is investigated here in a rodent model of human foraging and hoarding. The results of the proposed experiments will form the basis for novel pharmacological and/or behavioral therapies to decrease the quantities of stored foods thereby decreasing the opportunity and increasing the effort required to overeat, with implications for drug seeking/stashing as well.
|Alex Thomas, M; Tran, Vy; Ryu, Vitaly et al. (2017) AgRP knockdown blocks long-term appetitive, but not consummatory, feeding behaviors in Siberian hamsters. Physiol Behav :|
|Alex Thomas, M; Xue, Bingzhong (2017) Mechanisms for AgRP neuron-mediated regulation of appetitive behaviors in rodents. Physiol Behav :|
|Thomas, Michael A; Ryu, Vitaly; Bartness, Timothy J (2016) Central ghrelin increases food foraging/hoarding that is blocked by GHSR antagonism and attenuates hypothalamic paraventricular nucleus neuronal activation. Am J Physiol Regul Integr Comp Physiol 310:R275-85|
|Labbé, Sebastien M; Caron, Alexandre; Lanfray, Damien et al. (2015) Hypothalamic control of brown adipose tissue thermogenesis. Front Syst Neurosci 9:150|
|Teubner, Brett J W; Leitner, Claudia; Thomas, Michael A et al. (2015) An intact dorsomedial posterior arcuate nucleus is not necessary for photoperiodic responses in Siberian hamsters. Horm Behav 70:22-9|
|Garretson, John T; Teubner, Brett J W; Grove, Kevin L et al. (2015) Peroxisome proliferator-activated receptor ? controls ingestive behavior, agouti-related protein, and neuropeptide Y mRNA in the arcuate hypothalamus. J Neurosci 35:4571-81|
|Evans, Jennifer A; Suen, Ting-Chung; Callif, Ben L et al. (2015) Shell neurons of the master circadian clock coordinate the phase of tissue clocks throughout the brain and body. BMC Biol 13:43|
|Ryu, Vitaly; Garretson, John T; Liu, Yang et al. (2015) Brown adipose tissue has sympathetic-sensory feedback circuits. J Neurosci 35:2181-90|
|Douris, Nicholas; Stevanovic, Darko M; Fisher, Ffolliott M et al. (2015) Central Fibroblast Growth Factor 21 Browns White Fat via Sympathetic Action in Male Mice. Endocrinology 156:2470-81|
|Garretson, John T; Bartness, Timothy J (2014) Dynamic modification of hoarding in response to hoard size manipulation. Physiol Behav 127:8-12|
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