Featured Articles

Volume 22 | April 2019

Silver nanoparticles inhibit beige fat function and promote adiposityNanoparticles, ultrafine particles of 1 to 100 nm in size, show unique optical, electrical, or thermal properties. The recent decade has seen an exponential growth in the fabrication of nanoparticles, commonly termed as engineered nanoparticles (ENPs). Silver nanoparticles (AgNPs) are among the most widely used ENPs. However, concerns have been raised about their safety and potential influence on human health. The potential contribution of AgNPs specifically to obesity as well as the underlying mechanism have not yet been addressed. Yue, Zhao, Wang, et al. studied the in vitro effects of AgNPs on beige adipocyte differentiation and function, as well as their in vivo influence on beige fat and metabolic parameters of mice on a high fat diet. Their results show that AgNPs suppress beige adipocyte development and function. This suggests that environmental exposure with AgNPs may contribute to the obesity epidemic.

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Analysis of white and brown adipose tissue by shotgun lipidomicsThe two main forms of adipose tissue (AT) are white adipose tissue (WAT), which functions primarily as an energy reservoir, and brown adipose tissue (BAT), which contributes to thermoregulation. AT lipidomics analyses have reported differences between BAT and WAT and demonstrated remodeling upon exercise or cold exposure. However, these studies applied generic methods of lipid extraction and measurement rather than techniques tailored to these tissues. Grzybek, Palladini, et al. present a shotgun lipidomics method for the analysis for ATs with an unprecedented coverage of more than 300 lipid species. With their method, they not only observe clear differences between BAT and WAT lipidomes, but also amongst WAT subtypes, i.e. gonadal and inguinal subcutaneous ATs.

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Membrane metallo-endopeptidase regulates inflammatory response and insulin signaling Membrane metallo-endopeptidase (MME) is a membrane-bound protein with an extracellular protease domain. Ramirez et al. show that MME has distinct roles in white preadipocytes. MME can target a broad class of inflammatory cytokines, thus its high expression in subcutaneous preadipocytes may serve to decrease inflammatory responses. MME can also regulate receptor trafficking, suggesting a cellular role in insulin signaling.

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The BAT glucagon receptor is functional but not essential for control of energy homeostasisThe principal biological role of pancreatic glucagon is the maintenance of euglycemia through its control of hepatic glucose production. However, the glucagon receptor is not only expressed in hepatocytes but also in brown adipose tissue (BAT) and other tissues. Beaudry et al. examined the importance of the BAT glucagon receptor for glucagon-stimulated energy expenditure in mice. They show that, although the BAT glucagon receptor is functional, it is not essential for glucagon-stimulated increase in energy expenditure or the adaptive metabolic responses to high fat diet feeding or prolonged cold exposure.

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Pnpla3 silencing ameliorates NASH and fibrosis in Pnpla3 I148M knock-in miceNonalcoholic fatty liver disease (NAFLD) is becoming the leading cause of chronic liver disease worldwide. The progression of NAFLD has a strong genetic component. A polymorphism in the patatin-like phospholipase domain-containing 3 (PNPLA3) gene resultig in a change from isoleucine (I) to methionine (M) at position 148 of the protein exerts the largest effect on NAFLD progression identified to date. Lindén and colleagues show that Pnpla3 silencing exerts a beneficial effect on liver fat accumulation, inflammation, and fibrosis that is more pronounced in the presence of the Pnpla3 I148M mutation.

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Activation of hepatic ER-α increases energy expenditure by stimulating FGF21 productionEstrogens help maintain energy homeostasis in both male and female rodents and humans. After menopause, estrogen-deficient women are predisposed to metabolic dysfunction. Fibroblast growth factor 21 (FGF21), a hormone mainly produced by the liver during fasting, shows multiple beneficial effects in obese and diabetic individuals. Allard et al. show that in female mice, treatment with exogenous estrogen acting on the hepatocyte estrogen receptor-α increases serum FGF21 concentrations. In these mice, exogenous estrogen stimulates energy expenditure at least partially via FGF21. However, these results were not reproduced in an observational cohort of menopausal women who received estrogen therapy.

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Functional peroxisomes are required for β-cell integrity in micePeroxisomes are still enigmatic organelles six decades after their discovery. Their importance for pancreatic β-cell function remains largely unexplored. Baboota, Shinde, and colleagues assessed the abundance of peroxisomes in the endocrine pancreas and used an in vivo loss-of-function approach to investigate the role of peroxisomes in pancreatic β-cells. They provide evidence that peroxisomal metabolism plays an essential role in the preservation of β-cell integrity. This suggests that enhancing peroxisome activity is a potential avenue to support β-cell function in metabolic stress conditions.

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miR-132-3p is a positive regulator of alpha-cell mass miRNAs are small non-coding RNAs that regulate the expression of target genes by inhibiting translation or by inducing mRNA degradation. Several studies have illustrated the importance of miRNAs in glucose homeostasis. Dusaulcy et al. hypothesized that miRNAs are involved in alpha-cell molecular and functional alterations or adaptations in type 2 diabetes. They identified 16 miRNAs in alpha-cells and 28 in beta-cells differentially regulated according to diet. The most highly differentially regulated miRNA in alpha-cells from hyperglycemic mice, miR-132-3p, was found to be involved in alpha-cell proliferation and survival.

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Synbiotic-driven improvement of metabolic disturbances is associated with changes in the gut microbiome The gut microbiota are thought to play a key role in the regulation of host metabolism. Modulation of the gut microbiome may have beneficial effects on metabolism in obese individuals. Ke et al. tested interventions that modulate the gut microbiome and found that a combination of living bacteria and substances that promote their growth, called a synbiotic, improved metabolic disturbances in diet-induced obese mice. This was associated with changes in the gut microbiome which they characterized using a multi-omics approach.

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Repeated cold exposures protect a mouse model of Alzheimer’s disease against cold-induced tau phosphorylationAlzheimer’s disease (AD) is a neurodegenerative disease characterized by disrupted cognitive functions and is diagnosed neuropathologically by the presence of tau-laden neurofibrillary tangles. Animal studies suggest that thermoregulatory deficits contribute to AD pathogenesis. Tournissac and colleagues corrected thermoregulatory impairments through brown adipose tissue stimulation by repeated cold exposures in a mouse model of AD. Indeed, they found improved glucose metabolism and protection against cold-induced tau phosphorylation in their model.

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Roles for STAT proteins in leptin actionLeptin, a peptide hormone produced by white adipose tissue in proportion to energy stores, plays a central role in the control of feeding and energy balance. Leptin acts via its receptor to activate several members of the signal transducer and activator of transcription (STAT) transcription factor family. Pan, Allison, and colleagues investigated the roles of STAT1, STAT3 and STAT5 in response to leptin. Although leptin receptor activates STAT1, STAT3, and STAT5 in cultured cells, their findings reveal no role for STAT1 or STAT5 in leptin action in vivo.

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WWOX ablation in skeletal muscles alters glucose metabolismWWOX is a tumor suppressor that is commonly lost in several human malignancies. Several reports have implicated WWOX function in cellular metabolism. Abu-Remaileh et al. screened for the metabolic function of WWOX using engineered mouse models in which the murine Wwox gene was specifically deleted in the main metabolic peripheral organs including liver, adipose tissue, and skeletal muscle. They found that only mice with skeletal muscle-specific ablation of Wwox develop a phenotype resembling metabolic syndrome, as manifested by hyperglycemia, obesity, and dyslipidemia.

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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.



Amna Khamis
University of Lille, CNRS, Institute Pasteur de Lille, Lille, France
Referring article

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