Inefficient physiological transitions are known to cause metabolic disorders. Therefore, investigating mechanisms that constitute molecular switches in a central metabolic organ like the liver becomes crucial. Specifically, upstream mechanisms that control temporal engagement of transcription factors, which are essential to mediate physiological fed–fast–refed transitions are less understood. SIRT1, a NAD+-dependent deacetylase, is pivotal in regulating hepatic gene expression and has emerged as a key therapeutic target. Despite this, if/how nutrient inputs regulate SIRT1 interactions, stability, and therefore downstream functions are still unknown. Here, we establish nutrient-dependent O-GlcNAcylation of SIRT1, within its N-terminal domain, as a crucial determinant of hepatic functions. Our findings demonstrate that during a fasted-to-refed transition, glycosylation of SIRT1 modulates its interactions with various transcription factors and a nodal cytosolic kinase involved in insulin signaling. Moreover, sustained glycosylation in the fed state causes nuclear exclusion and cytosolic ubiquitin-mediated degradation of SIRT1. This mechanism exerts spatiotemporal control over SIRT1 functions by constituting a previously unknown molecular relay. Of note, loss of SIRT1 glycosylation discomposed these interactions resulting in aberrant gene expression, mitochondrial dysfunctions, and enhanced hepatic gluconeogenesis. Expression of nonglycosylatable SIRT1 in the liver abrogated metabolic flexibility, resulting in systemic insulin resistance, hyperglycemia, and hepatic inflammation, highlighting the physiological costs associated with its overactivation. Conversely, our study also reveals that hyperglycosylation of SIRT1 is associated with aging and high-fat–induced obesity. Thus, we establish that nutrient-dependent glycosylation of SIRT1 is essential to gate its functions and maintain physiological fitness.

This paper provides an overview of stable isotope analysis (H, C, N, O, Si) of the macroand microscopic remains from aquatic organisms found in lake sediment records and their application in (palaeo)environmental science. Aquatic organisms, including diatoms, macrophytes, invertebrates, and fish, can produce sufficiently robust remains that preserve well as fossils and can be identified in lake sediment records. Stable isotope analyses of these remains can then provide valuable insights into habitat-specific biogeochemistry, feeding ecology, but also on climatic and hydrological changes in and around lakes. Since these analyses focus on the remains of known and identified organisms, they can provide more specific and detailed information on past ecosystem, food web and environmental changes affecting different compartments of lake ecosystems than analyses on bulk sedimentary organic matter or carbonate samples. We review applications of these types of analyses in palaeoclimatology, palaeohydrology, and palaeoecology. Interpretation of the environmental 'signal' provided by taxon-specific stable isotope analysis requires a thorough understanding of the ecology and phenology of the organism groups involved. Growth, metabolism, diet, feeding strategy, migration, taphonomy and several other processes can lead to isotope fractionation or otherwise influence the stable isotope signatures of the remains from aquatic organisms. This paper includes a review of the (modern) calibration, culturing and modeling studies used to quantify the extent to which these factors influence stable isotope values and provides an outlook for future research and methodological developments for the different examined fossil groups.

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