Other: Metabolism

Type 2 diabetes is associated with increased circulating levels of 3-hydroxydecanoate activating GPR84 and neutrophil migration

Obesity and diabetes are associated with inflammation and altered plasma levels of several metabolites, which may be involved in disease progression. Some metabolites can activate G protein-coupled receptors (GPCRs) expressed on immune cells where they can modulate metabolic inflammation. Here we find that 3-hydroxydecanoate is enriched in the circulation of obese individuals with type 2 diabetes (T2D) compared with non-diabetic controls.

Raphe serotonin projections dynamically regulate feeding behavior through targeting inhibitory circuits from rostral zona incerta to paraventricular thalamus

Rostral zona incerta (ZIR) evokes feeding by sending GABA transmission to paraventricular thalamus (PVT). Although central serotonin (5-HT) signaling is known to play critical roles in the regulation of food intake and eating disorders, it remains unknown whether raphe 5-HT neurons functionally innervate ZIR-PVT neural pathway for feeding control.

A Cre-driver rat model for anatomical and functional analysis of glucagon (Gcg)-expressing cells in the brain and periphery

The glucagon gene (Gcg) encodes preproglucagon, which is cleaved to form glucagon-like peptide 1 (GLP1) and other mature signaling molecules implicated in metabolic functions. To date there are no transgenic rat models available for precise manipulation of GLP1-expressing cells in the brain and periphery.To visualize and manipulate Gcg-expressing cells in rats, CRISPR/Cas9 was used to express iCre under control of the Gcg promoter. Gcg-Cre rats were bred with tdTomato reporter rats to tag Gcg-expressing cells.

An Early Islet Transcriptional Signature is Associated with Local Inflammation in Autoimmune Diabetes

Identifying the early islet cellular processes of autoimmune type 1 diabetes (T1D) in humans is challenging given the absence of symptoms during this period and the inaccessibility of the pancreas for sampling. Here, we study temporal events in pancreatic islets in LEW.1WR1 rats, in which autoimmune diabetes can be induced with virus infection, by performing transcriptional analysis of islets harvested during the pre-diabetic period.

Acute changes in systemic glycemia gate access and action of GLP-1R agonist on brain structures controlling energy homeostasis

Therapies based on glucagon-like peptide-1 (GLP-1) long-acting analogs and insulin are often used in the treatment of metabolic diseases. Both insulin and GLP-1 receptors are expressed in metabolically relevant brain regions, suggesting a cooperative action. However, the mechanisms underlying the synergistic actions of insulin and GLP-1R agonists remain elusive. In this study, we show that insulin-induced hypoglycemia enhances GLP-1R agonists entry in hypothalamic and area, leading to enhanced whole-body fat oxidation.

Nutrient metabolism of the nucleus pulposus: A literature review

Cells take in, consume, and synthesize nutrients for numerous physiological functions. This includes not only energy production but also macromolecule biosynthesis, which will further influence cellular signaling, redox homeostasis, and cell fate commitment. Therefore, alteration in cellular nutrient metabolism is associated with pathological conditions. Intervertebral discs, particularly the nucleus pulposus (NP), are avascular and exhibit unique metabolic preferences.

Metabolic cues impact non-oscillatory intergeniculate leaflet and ventral lateral geniculate nucleus: standard vs high-fat diet comparative study

The intergeniculate leaflet and ventral lateral geniculate nucleus (IGL/VLG) of the rodent thalamus process various signals and participate in circadian entrainment In both structures, cells exhibiting infra-slow oscillatory activity as well as non-rhythmically firing neurons can be observed Here, we reveal that only one of these two groups of cells responds to anorexigenic (CCK, GLP-1 and OXM) and orexigenic (Ghrl and OXA) peptides. Neuronal responses vary depending on the time of day (day vs. night) and on the diet (standard vs.

Full activation of thermogenesis in brown adipocytes requires Basigin action

Exploring mechanisms responsible for brown adipose tissue's (BAT) high metabolic activity is crucial to exploit its energy-dissipating ability for therapeutic purposes. Basigin (Bsg), a multifunctional highly glycosylated transmembrane protein, was recently proposed as one of the 98 critical markers allowing to distinguish 'white' and 'brown' adipocytes, yet its function in thermogenic brown adipocytes is unknown. Here, we report that Bsg is negatively associated with obesity in mice. By contrast, Bsg expression increased in the mature adipocyte fraction of BAT upon cold acclimation.

A Spatial Atlas of Wnt Receptors in Adult Mouse Liver

Hepatic zonation is critical for most metabolic functions in liver. Wnt signaling plays an important role in establishing and maintaining liver zonation. Yet, the anatomic expression of Wnt signaling components, especially all 10 Frizzled (Fzd) receptors, has not been characterized in adult liver. To address this, we quantitatively mapped the spatial expression of Fzd receptors in adult mouse liver via multiplex fluorescent in situ hybridization. Although all 10 Fzd receptors are expressed within a metabolic unit, Fzd receptors 1, 4, and 6 are the highest expressed.

Osmoadaptive GLP-1R signalling in hypothalamic neurones inhibits antidiuretic hormone synthesis and release

The excessive release of the antidiuretic hormone vasopressin is implicated in many diseases including cardiovascular disease, diabetes, obesity, and metabolic syndrome. Once thought to be elevated as a consequence of diseases, data now supports a more causative role. We have previously identified CREB3L1 as a transcription factor that co-ordinates vasopressin synthesis and release in the hypothalamus. The objective here was to identify mechanisms orchestrated by CREB3L1 that co-ordinate vasopressin release.We mined Creb3l1 knockdown SON RNA-seq data to identify downstream target genes.

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