Featured Articles

Volume 6 | No. 4 | April 2017

Changes in adipose tissue macrophage and T cells after sleeve gastrectomyBariatric surgery is currently the most successful treatment for obesity and is the only therapeutic option that also causes sustained substantial reduction of type 2 diabetes. Frikke-Schmidt and colleagues found that vertical sleeve gastrectomy (VSG) in mice altered the immune cell populations residing in the epididymal white adipose tissue in a weight-independent manner. The CD11c- adipose tissue macrophage population increased in number, while different T cell populations expanded 3-fold. These strong, weight-independent changes in immune populations after surgery suggest that the immune system could play a significant role in the weight-independent adipose metabolic improvements observed after VSG in rodents.

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DNA methylation contributes to pathophysiology in mice fed a high fat dietGenetics and environment contribute to the development of obesity and its associated disorders. The interactions between epigenetic changes and obesity in metabolically relevant tissues, such as liver, however, are not well understood. One particularly important epigenetic mark is DNA methylation, associated with repressed chromatin states. Zhang et al. show that a high fat diet alters hepatic DNA methylation, transcription, and gene expression patterns, which contributes to the pathophysiology of obesity.

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A role for Elovl2 in glucose-induced insulin secretionHigh fat-high sucrose (HFHS) diet-fed mice become severely glucose intolerant, and insulin resistance progressively worsens with time. However, the development and severity of the diabetic phenotype depends on several factors, including the choice of genetic background. Cruciani-Guglielmacci, Bellini et al. analyzed in parallel the effect of a HFHS diet on six commonly used laboratory mouse strains using carefully controlled housing and experimental conditions. The strains show marked differences in susceptibility to diet-induced obesity and β-cell failure. This approach provides evidence that Elongase of very long-chain fatty acids 2 (Elovl2), an enzyme involved in very long chain fatty acid synthesis, is a key player in regulating glucose-stimulated insulin secretion in the context of β-cell dysfunction.

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mRNA sequencing of skeletal muscle: search for exercise-regulated myokines Proteins and peptides produced by and released from skeletal muscles are termed myokines, and several myokines play important roles in muscle physiology as well as in tissue cross talk. Pourteymour and colleagues used mRNA sequencing to identify numerous transcripts that were regulated in skeletal muscle after acute and/or long-term exercise. These transcripts encode potential myokines, which may play key roles in local and systemic adaptations to exercise. Furthermore, they identified CSF1 as a novel myokine, which was increased after acute and long-term exercise and secreted from cultured human myotubes in response to electrical pulse stimulation.

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Astrocyte signaling is required for obesity and inflammationObesity and excessive dietary consumption promote upregulation of the master inflammatory NF-κB pathway in important brain regions including the hypothalamus. While several studies have implicated microglia in the generation of diet-induced inflammatory signals and metabolic dysfunction, a similar role for astrocytes remains unclear. To address this, Douglass et al. developed a mouse model with an inducible astrocyte-specific deletion of IKKβ. Using this approach, they demonstrate that reduction of astrocyte inflammatory signaling protects mice from high fat diet-induced hypothalamic inflammation and reduces susceptibility to diet induced obesity and glucose intolerance.

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Cannabinoid receptor-containing axons innervate NPY/AgRP neurons Cannabinoid type 1 receptors (CB1R) mediate the effects of cannabinoids on energy metabolism. Neurons in the hypothalamic arcuate nucleus (ARC) that coexpress Agouti-related protein (AgRP) and neuropeptide Y (NPY) also affect whole body energy metabolism. Morozov et al. used transgenic mouse models and methods of electron microscopy combined with 3D reconstruction to evaluate the morphological substrate of presynaptic CB1R dependent control of AgRP/NPY neurons in the ARC. They find that eCBs and cannabis drugs may conduct prandial mechanisms through retrograde synaptic dis-inhibition and dis-excitation in the hypothalamus.

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The 60 Second Metabolist
In this section authors briefly report on their work recently published in Molecular Metabolism.

Watch the most recent interview by clicking the video still. The link "referring article" directs you to this author's publication.



Ursula Neumann
University of British Columbia, Vancouver, Canada
Referring article

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