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- Andersson, Björn, et al.
(author)
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O-GlcNAc cycling mediates energy balance by regulating caloric memory
- 2021
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In: Appetite. - : Elsevier. - 0195-6663 .- 1095-8304. ; 165
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Journal article (peer-reviewed)abstract
- 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.
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- Banerjee, Partha S., et al.
(author)
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Roles of O-GlcNAc in chronic diseases of aging
- 2016
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In: Molecular Aspects of Medicine. - : Elsevier. - 0098-2997 .- 1872-9452. ; 51, s. 1-15
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Research review (peer-reviewed)abstract
- O-GlcNAcylation, a dynamic nutrient and stress sensitive post-translational modification, occurs on myriad proteins in the cell nucleus, cytoplasm and mitochondria. O-GlcNAcylation serves as a nutrient sensor to regulate signaling, transcription, translation, cell division, metabolism, and stress sensitivity in all cells. Aberrant protein O-GlcNAcylation plays a critical role both in the development, as well as in the progression of a variety of age related diseases. O-GlcNAcylation underlies the etiology of diabetes, and changes in specific protein O-GlcNAc levels and sites are responsible for insulin expression and sensitivity and glucose toxicity. Abnormal O-GlcNAcylation contributes directly to diabetes related dysfunction of the heart, kidney and eyes and affects progression of cardiomyopathy, nephropathy and retinopathy. O-GlcNAcylation is a critical modification in the brain and plays a role in both plaque and tangle formation, thus making its study important in neurodegenerative disorders. O-GlcNAcylation also affects cellular growth and metabolism during the development and metastasis of cancer. Finally, alterations in O-GlcNAcylation of transcription factors in macrophages and lymphocytes affect inflammation and cytokine production. Thus, O-GlcNAcylation plays key roles in many of the major diseases associated with aging. Elucidation of its specific functions in both normal and diseased tissues is likely to uncover totally novel avenues for therapeutic intervention.
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- Hart, Gerald W., et al.
(author)
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Cross Talk Between O-GlcNAcylation and Phosphorylation: Roles in Signaling, Transcription, and Chronic Disease
- 2011
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In: Annual Review of Biochemistry. - : Annual Reviews. - 0066-4154 .- 1545-4509. ; 50, s. 825-858
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Journal article (other academic/artistic)abstract
- O-GlcNAcylation is the addition of β-D-N-acetylglucosamine to serine or threonine residues of nuclear and cytoplasmic proteins. O-linked N-acetylglucosamine (O-GlcNAc) was not discovered until the early 1980s and still remains difficult to detect and quantify. Nonetheless, O-GlcNAc is highly abundant and cycles on proteins with a timescale similar to protein phosphorylation. O-GlcNAc occurs in organisms ranging from some bacteria to protozoans and metazoans, including plants and nematodes up the evolutionary tree to man. O-GlcNAcylation is mostly on nuclear proteins, but it occurs in all intracellular compartments, including mitochondria. Recent glycomic analyses have shown that O-GlcNAcylation has surprisingly extensive cross talk with phosphorylation, where it serves as a nutrient/stress sensor to modulate signaling, transcription, and cytoskeletal functions. Abnormal amounts of O-GlcNAcylation underlie the etiology of insulin resistance and glucose toxicity in diabetes, and this type of modification plays a direct role in neurodegenerative disease. Many oncogenic proteins and tumor suppressor proteins are also regulated by O-GlcNAcylation. Current data justify extensive efforts toward a better understanding of this invisible, yet abundant, modification. As tools for the study of O-GlcNAc become more facile and available, exponential growth in this area of research will eventually take place.
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- Lagerlöf, Jan, et al.
(author)
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Earthworms influenced by reduced tillage, conventional tillage and energy forest in Swedish agricultural field experiments
- 2012
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In: Acta Agriculturae Scandinavica, Section B - Soil and Plant Science. - : Informa UK Limited. - 0906-4710 .- 1651-1913. ; 62, s. 235-244
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Journal article (peer-reviewed)abstract
- We compared earthworm density, depth distribution and species composition in three soil cultivation experiments including the treatments ploughless tillage and mouldboard ploughing. Sampling was done in September 2005 and for one experiment also in 1994. By yearly sampling 1995-2005, earthworms in an energy forest of Salix viminalis were compared with those in an adjacent arable field. Sampling method was digging of soil blocks and hand sorting and formalin sampling in one cultivation experiment. Both methods were used in the energy forest and arable land comparison.In two soil cultivation experiments, highest abundances or biomass were found in ploughless tillage. Earthworm density was higher in the upper 10 cm, especially in the ploughless tillage. Earthworm density was significantly higher in the energy forest than in the arable field. Formalin sampling revealed c. 36% of the earthworm numbers found by digging in the energy forest and gave almost no earthworms in the arable field. In all treatments with soil cultivation, species living and feeding in the rhizosphere and soil dominated. One such species, Allolobophora chlorotica, was more abundant under mouldboard ploughing than ploughless tillage. Lumbricus terrestris, browsing on the surface and producing deep vertical burrows, was more common in the ploughless tillage. Species living and feeding close to the soil surface were almost only found in the energy forest, which had not been soil cultivated since 1984.The findings support earlier studies pointing out possibilities to encourage earthworms by reduced soil cultivation. This is one of the first published studies that followed earthworm populations in an energy forest plantation during several years. Explanation of earthworm reactions to management and environmental impacts should be done with consideration of the ecology of species or species groups. Earthworm sampling by formalin must always be interpreted with caution and calibrated by digging and hand-sorting sampling.
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| 8. |
- Lagerlöf, Olof
(author)
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O-GlcNAc cycling in the developing, adult and geriatric brain
- 2018
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In: Journal of Bioenergetics and Biomembranes. - : Springer-Verlag New York. - 0145-479X .- 1573-6881. ; 50:3, s. 241-261
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Journal article (peer-reviewed)abstract
- Hundreds of proteins in the nervous system are modified by the monosaccharide O-GlcNAc. A single protein is often O-GlcNAcylated on several amino acids and the modification of a single site can play a crucial role for the function of the protein. Despite its complexity, only two enzymes add and remove O-GlcNAc from proteins, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Global and local regulation of these enzymes make it possible for O-GlcNAc to coordinate multiple cellular functions at the same time as regulating specific pathways independently from each other. If O-GlcNAcylation is disrupted, metabolic disorder or intellectual disability may ensue, depending on what neurons are affected. O-GlcNAc's promise as a clinical target for developing drugs against neurodegenerative diseases has been recognized for many years. Recent literature puts O-GlcNAc in the forefront among mechanisms that can help us better understand how neuronal circuits integrate diverse incoming stimuli such as fluctuations in nutrient supply, metabolic hormones, neuronal activity and cellular stress. Here the functions of O-GlcNAc in the nervous system are reviewed.
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- Lagerlöf, Olof, et al.
(author)
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O-GlcNAc transferase regulates excitatory synapse maturity
- 2017
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In: Proceedings of the National Academy of Sciences of the United States of America. - Washington : National Academy of Science of the United States of America. - 0027-8424 .- 1091-6490. ; 114:7, s. 1684-1689
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Journal article (peer-reviewed)abstract
- Experience-driven synaptic plasticity is believed to underlie adaptive behavior by rearranging the way neuronal circuits process information. We have previously discovered that O-GlcNAc transferase (OGT), an enzyme that modifies protein function by attaching β-N-acetylglucosamine (GlcNAc) to serine and threonine residues of intracellular proteins (O-GlcNAc), regulates food intake by modulating excitatory synaptic function in neurons in the hypothalamus. However, how OGT regulates excitatory synapse function is largely unknown. Here we demonstrate that OGT is enriched in the postsynaptic density of excitatory synapses. In the postsynaptic density, O-GlcNAcylation on multiple proteins increased upon neuronal stimulation. Knockout of the OGT gene decreased the synaptic expression of the AMPA receptor GluA2 and GluA3 subunits, but not the GluA1 subunit. The number of opposed excitatory presynaptic terminals was sharply reduced upon postsynaptic knockout of OGT. There were also fewer and less mature dendritic spines on OGT knockout neurons. These data identify OGT as a molecular mechanism that regulates synapse maturity.
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| 10. |
- Lagerlöf, Olof, et al.
(author)
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O-GlcNAcylation of Neuronal Proteins : Roles in Neuronal Functions and in Neurodegeneration
- 2014
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In: Glycobiology of the Nervous System. - New York : Springer. - 9781493911530 - 9781493911547 ; , s. 343-366
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Book chapter (other academic/artistic)abstract
- O-GlcNAc is the attachment of β-N-acetylglucosamine to the hydroxyl group of serine and threonine in nuclear and cytoplasmic proteins. It is generally not further elongated but exists as a monosaccharide that can be rapidly added or removed. Thousands of proteins involved in gene transcription, protein translation, and degradation as well as the regulation of signal transduction contain O-GlcNAc. Brain is one of the tissues where O-GlcNAc is most highly expressed and deletion of neuronal O-GlcNAc leads to death early in development. O-GlcNAc is also important for normal adult brain function, where dynamic processes like learning and memory at least in part depend on the modification of specific proteins by O-GlcNAc. Conversely, too much or too little O-GlcNAc on other proteins participates in neurodegenerative processes underlying diseases such as Alzheimer’s and Parkinson’s. In this chapter, we describe the expression and regulation of O-GlcNAc in the nervous system.
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