title: Metabolic learning and memory formation by the brain influence systemic metabolic homeostasis.
abstract: Metabolic homeostasis is regulated by the brain, but whether this regulation involves learning and memory of metabolic information remains unexplored. Here we use a calorie-based, taste-independent learning/memory paradigm to show that Drosophila form metabolic memories that help in balancing food choice with caloric intake; however, this metabolic learning or memory is lost under chronic high-calorie feeding. We show that loss of individual learning/memory-regulating genes causes a metabolic learning defect, leading to elevated trehalose and lipid levels. Importantly, this function of metabolic learning requires not only the mushroom body but also the hypothalamus-like pars intercerebralis, while NF-κB activation in the pars intercerebralis mimics chronic overnutrition in that it causes metabolic learning impairment and disorders. Finally, we evaluate this concept of metabolic learning/memory in mice, suggesting that the hypothalamus is involved in a form of nutritional learning and memory, which is critical for determining resistance or susceptibility to obesity. In conclusion, our data indicate that the brain, and potentially the hypothalamus, direct metabolic learning and the formation of memories, which contribute to the control of systemic metabolic homeostasis.
authors.affiliation: 1] Department of Molecular Pharmacology, Diabetes Research Center, Institute of Aging, Albert Einstein College of Medicine, Bronx, New York 10461, USA [2] Department of Endocrinology and Metabolism, the First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Yumin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Molecular Pharmacology, Diabetes Research Center, Institute of Aging, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Molecular Pharmacology, Diabetes Research Center, Institute of Aging, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Jingqi
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Molecular Pharmacology, Diabetes Research Center, Institute of Aging, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Yalin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Molecular Pharmacology, Diabetes Research Center, Institute of Aging, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Molecular Pharmacology, Diabetes Research Center, Institute of Aging, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Cai
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000378:metabolism*; D004330:Drosophila; D002149:Energy Intake; D006706:Homeostasis; D007031:Hypothalamus / Q000378:metabolism; D007858:Learning / Q000502:physiology; D050356:Lipid Metabolism; D008568:Memory / Q000502:physiology*; D051379:Mice; D024521:Mushroom Bodies / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D044343:Overnutrition / Q000378:metabolism / Q000523:psychology; D014199:Trehalose / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D014199:Trehalose
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