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O-GlcNAc cycling mediates energy balance by regulating caloric memory
Department of Pediatric Surgery, Uppsala University Hospital, Uppsala, Sweden.
Sanford Burnham Prebys Medical Discovery Institute, CA, United States.
Department of Pharmacology, Toxicology and Therapeutics, Kansas University, KS, United States.
Department of Pharmacology, Toxicology and Therapeutics, Kansas University, KS, United States.
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2021 (Engelska)Ingår i: Appetite, ISSN 0195-6663, E-ISSN 1095-8304, Vol. 165, artikel-id 105320Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Caloric need has long been thought a major driver of appetite. However, it is unclear whether caloric need regulates appetite in environments offered by many societies today where there is no shortage of food. Here we observed that wildtype mice with free access to food did not match calorie intake to calorie expenditure. While the size of a meal affected subsequent intake, there was no compensation for earlier under- or over-consumption. To test how spontaneous eating is subject to caloric control, we manipulated O-linked β-N-acetylglucosamine (O-GlcNAc), an energy signal inside cells dependent on nutrient access and metabolic hormones. Genetic and pharmacological manipulation in mice increasing or decreasing O-GlcNAcylation regulated daily intake by controlling meal size. Meal size was affected at least in part due to faster eating speed. Without affecting meal frequency, O-GlcNAc disrupted the effect of caloric consumption on future intake. Across days, energy balance was improved upon increased O-GlcNAc levels and impaired upon removal of O-GlcNAcylation. Rather than affecting a perceived need for calories, O-GlcNAc regulates how a meal affects future intake, suggesting that O-GlcNAc mediates a caloric memory and subsequently energy balance.

Ort, förlag, år, upplaga, sidor
Elsevier, 2021. Vol. 165, artikel-id 105320
Nyckelord [en]
Appetite, Feeding behavior, Food intake, Learning and memory, O-GlcNAc, Obesity, Set point
Nationell ämneskategori
Biokemi och molekylärbiologi
Identifikatorer
URN: urn:nbn:se:umu:diva-184201DOI: 10.1016/j.appet.2021.105320ISI: 000670055500008Scopus ID: 2-s2.0-85106903106OAI: oai:DiVA.org:umu-184201DiVA, id: diva2:1565740
Forskningsfinansiär
Knut och Alice Wallenbergs StiftelseRegion VästerbottenTillgänglig från: 2021-06-14 Skapad: 2021-06-14 Senast uppdaterad: 2023-09-05Bibliografiskt granskad

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Lagerlöf, Olof

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Institutionen för integrativ medicinsk biologi (IMB)Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM)Psykiatri
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