Featured Articles

Volume 5 | No. 1 | January 2016

Adipose tissue glycogen accumulation is associated with obesity-linked inflammationThe study of Ceperuelo-Mallafré, Ejarque and colleagues provide the first evidence of adipose tissue glycogen as an inflammatory signal, which might underlie the pathogenesis of obesity and insulin resistance. They postulate that in an obesity setting, a shift from glycolytic metabolism to glycogenesis occurs in adipose tissue, which directly determines the secretory function of adipocytes by a mechanism dependent on autophagy flux activation, as well as an increase in the M1 polarized macrophage population. The study suggests a metabolic disturbance in adipocytes as a potential primary event in obesity-related inflammation that should be considered in the development of new therapeutic strategies to alleviate obesity-associated metabolic disorders.

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Stress-induced activation of brown adipose tissue prevents obesityStress and negative affect are increasingly recognized as risk factors for eating disorders and obesity. Razzoli, Frontini, Gurney, and colleagues demonstrate that resilience to chronic subordination stress-induced obesity is determined by a pre-stress state of low adaptive thermogenesis and brown adipose tissue function. They identify a sympathetic/brown adipocyte purinergic pathway that is downregulated at thermoneutrality, which is induced by subordination stress and that mediates browning in brown adipocytes.

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Skeletal muscle salt inducible kinase 1 promotes insulin resistanceNixon and colleagues generate conditional salt inducible kinase 1 (SIK1) knockout mice and show that global deletion of SIK1 does not result in hyperglycemia or increased hepatic gluconeogenesis in vivo but a marked improvement in glucose tolerance, peripheral insulin sensitivity and skeletal muscle glucose uptake on high fat diet. They identify skeletal muscle as the site of SIK1 action required for development of full insulin resistance in obesity and provide the first evidence that SIK1 is a promising therapeutic target to improve peripheral insulin sensitivity in obese individuals.

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Incretin-like effects of small molecule trace amine-associated receptor 1 agonistsTrace amine-associated receptor 1 (TAAR1) is a G protein-coupled receptor belonging to the trace amine-associated receptor family. By using a selective small molecule agonist Raab et al. demonstrate beneficial metabolic consequences of specific TAAR1 activation. Their data support multiple effects of a selective TAAR1 agonist likely mediated by β-cells in the pancreas and enteroendocrine cells in the intestine. These findings suggest TAAR1 as a new target for the treatment of type 2 diabetes and obesity with an incretin-like mechanism of action amenable to orally delivered small molecule drugs.

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EBF2 promotes the recruitment of beige adipocytes in white adipose tissueA promising avenue to counteract weight gain is through increasing the activity of thermogenic brown and beige adipocytes. Stine et al. report that Early B-Cell Factor-2 (EBF2) controls beige adipocyte development in white adipose tissue (WAT). The genetic loss of Ebf2 in mice blocks beige fat development and function without having any other obvious effects on WAT. EBF2 could potentially be manipulated to improve overall systemic metabolism in mice.

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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.



Randy J. Seeley, Henriette Frikke-Schmidt
University of Michigan Health System, Ann Arbor, USA
Referring article

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Translational and Therapeutic Perspectives of Brown Adipose
Copenhagen, Denmark
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