Epigenetic Regulation of Diabetogenic Adipose Morphology
ConclusionCpG methylation could be influential in determining adipose morphology and thereby constitute a novel antidiabetic target. We identified C14orf180 as a novel regulator of adipocyte lipid storage and possibly differentiation. (Source: Molecular Metabolism)
Source: Molecular Metabolism - April 18, 2019 Category: Endocrinology Source Type: research

Editorial Board, cover figure description and credits
Publication date: May 2019Source: Molecular Metabolism, Volume 23Author(s): (Source: Molecular Metabolism)
Source: Molecular Metabolism - April 18, 2019 Category: Endocrinology Source Type: research

SIRT3 controls brown fat thermogenesis by deacetylation regulation of pathways upstream of UCP1
ConclusionsOur data highlight that SIRT3 likely controls BAT thermogenesis indirectly by targeting pathways upstream of UCP1. (Source: Molecular Metabolism)
Source: Molecular Metabolism - April 17, 2019 Category: Endocrinology Source Type: research

Maternal Western-style diet affects offspring islet composition and function in a non-human primate model of maternal over-nutrition
ConclusionsMaternal WSD exposure results in persistently decreased α-cell mass in the three-year old offspring. WSD/CTR islets secreted greater amounts of insulin ex vivo, suggesting that these islets are primed to hyper-secrete insulin under certain metabolic stressors. Although WSD did not induce overt impaired glucose tolerance in dams or offspring, offspring born to mothers with higher glucose excursions during a glucose tolerance test were more likely to also show higher glucose excursions. (Source: Molecular Metabolism)
Source: Molecular Metabolism - April 14, 2019 Category: Endocrinology Source Type: research

JUND regulates pancreatic β cell survival during metabolic stress
ConclusionsA translation-centric approach uncovered JUND as a stress-responsive factor in β cells that contributes to redox imbalance and apoptosis during pathophysiologically relevant stress. (Source: Molecular Metabolism)
Source: Molecular Metabolism - April 12, 2019 Category: Endocrinology Source Type: research

Reduced insulin action in muscle of high fat diet rats over the diurnal cycle is not associated with defective insulin signaling
ConclusionThese studies suggest that reduced glucose uptake in muscle during the diurnal cycle induced by short-term HFHS-feeding is not the result of reduced insulin signaling. (Source: Molecular Metabolism)
Source: Molecular Metabolism - April 12, 2019 Category: Endocrinology Source Type: research

Gsα deficiency in the dorsomedial hypothalamus leads to obesity, hyperphagia, and reduced thermogenesis associated with impaired leptin signaling
ConclusionsDMH Gsα signaling is critical for energy balance, thermogenesis, and leptin signaling. This study provides insight into how distinct signaling pathways can interact to regulate energy homeostasis and temperature regulation. (Source: Molecular Metabolism)
Source: Molecular Metabolism - April 12, 2019 Category: Endocrinology Source Type: research

Noggin Depletion in Adipocytes Promotes Obesity in Mice
ConclusionsBMP signaling regulates female and male adipogenesis through different metabolic pathways. Modulation of adipose tissue metabolism by select BMP antagonists may be a strategy for long-term regulation of age-related weight gain and obesity.Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - April 11, 2019 Category: Endocrinology Source Type: research

An actionable sterol-regulated feedback loop modulates statin sensitivity in prostate cancer
ConclusionOur study implicates statin-induced SREBP2 activation as a PCa vulnerability that can be exploited for therapeutic purposes using clinically-approved agents. (Source: Molecular Metabolism)
Source: Molecular Metabolism - April 11, 2019 Category: Endocrinology Source Type: research

Redox control of non-shivering thermogenesis
Publication date: Available online 10 April 2019Source: Molecular MetabolismAuthor(s): Daniele Lettieri-BarbatoAbstractBackgroundThermogenic adipocytes reorganize their metabolism during cold exposure. Metabolic reprogramming requires readily available bioenergetics substrates, such as glucose and fatty acids, to increase mitochondrial respiration and produce heat via the uncoupling protein 1 (UCP1). This condition generates a finely-tuned production of mitochondrial reactive oxygen species (ROS) that support non-shivering thermogenesis.Scope of ReviewHerein, the findings underlining the mechanisms that regulate ROS produc...
Source: Molecular Metabolism - April 10, 2019 Category: Endocrinology Source Type: research

What is the best housing temperature to translate mouse experiments to humans?
ConclusionWe concur with Fisher et al and others that 21 °C is too cool, but we continue to suggest that 30 °C is too warm. We support this with other data. Finally, to mimic living environments of all humans, and not just those in controlled Western environments, mouse experimentation at various temperatures is likely required.Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - April 6, 2019 Category: Endocrinology Source Type: research

Identification of functional lipid metabolism biomarkers of brown adipose tissue aging
ConclusionsOur functional analyses show that changes in specific lipid species, as observed during aging, may contribute to reduced thermogenic potential. They thus uncover potential biomarkers of aging as well as molecular mechanisms that could contribute to the degradation of brown adipocytes, thereby providing potential treatment strategies of age-related metabolic conditions. (Source: Molecular Metabolism)
Source: Molecular Metabolism - April 5, 2019 Category: Endocrinology Source Type: research

Dietary calories and lipids synergistically shape adipose tissue cellularity during postnatal growth
ConclusionsDietary lipids and calories differentially and synergistically drive adipose tissue proliferative growth and the programming of the metabolic syndrome in childhood. (Source: Molecular Metabolism)
Source: Molecular Metabolism - April 5, 2019 Category: Endocrinology Source Type: research

Profound weight loss induces reactive astrogliosis in the arcuate nucleus of obese mice
ConclusionsOverall, our data demonstrate that in a chronically obese state, astrocyte and microglial RG is indifferent from that observed in age-matched chow controls. Nonetheless, profound acute weight loss can induce astrocyte RG in the hypothalamic arcuate nucleus, possibly due to increased circulating NEFAs. This suggests that astrocytes may sense acute changes to both the dietary environment and body weight.Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - April 3, 2019 Category: Endocrinology Source Type: research

Editorial Board, cover figure description and credits
Publication date: April 2019Source: Molecular Metabolism, Volume 22Author(s): (Source: Molecular Metabolism)
Source: Molecular Metabolism - March 28, 2019 Category: Endocrinology Source Type: research

Ferritin Regulates Organismal Energy Balance and Thermogenesis
ConclusionThe FTH component of ferritin acts as a master regulator of organismal Fe homeostasis, coupling nutritional Fe supply to organismal redox homeostasis, energy expenditure and thermoregulation. (Source: Molecular Metabolism)
Source: Molecular Metabolism - March 22, 2019 Category: Endocrinology Source Type: research

Point mutations in the PDX1 transactivation domain impair human β-cell development and function
ConclusionsOur results reveal mechanistic details of how common coding mutations in PDX1 impair human pancreatic endocrine lineage formation and β-cell function and contribute to predisposition for diabetes. (Source: Molecular Metabolism)
Source: Molecular Metabolism - March 20, 2019 Category: Endocrinology Source Type: research

Adipose Lipocalin 2 Overexpression Protects Against Age-Related Decline In Thermogenic Function of Adipose Tissue and Metabolic Deterioration
ConclusionsWe demonstrate that overexpression of Lcn2 in adipose tissue not only preserves adipose tissue function during aging but also promotes maintenance of glucose tolerance, decreases dyslipidemia, and prevents liver lipid accumulation and steatosis. (Source: Molecular Metabolism)
Source: Molecular Metabolism - March 20, 2019 Category: Endocrinology Source Type: research

Laser capture microdissection of human pancreatic islets reveals novel eQTLs associated with type 2 diabetes
Publication date: Available online 18 March 2019Source: Molecular MetabolismAuthor(s): Amna Khamis, Mickaël Canouil, Afshan Siddiq, Hutokshi Crouch, Mario Falchi, Manon von Bulow, Florian Ehehalt, Lorella Marselli, Marius Distler, Daniela Richter, Jürgen Weitz, Krister Bokvist, Ioannis Xenarios, Bernard Thorens, Anke M. Schulte, Mark Ibberson, Amelie Bonnefond, Piero Marchetti, Michele Solimena, Philippe Froguel (Source: Molecular Metabolism)
Source: Molecular Metabolism - March 19, 2019 Category: Endocrinology Source Type: research

Heterogeneity in the perirenal region of humans suggests presence of dormant brown adipose tissue that contains brown fat precursor cells
ConclusionsWe propose that perirenal adipose tissue in adult humans consists mainly of dormant BAT and provide a data set for future research on factors which can reactivate dormant BAT into active BAT, a potential strategy for combatting obesity and metabolic disease.Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - March 16, 2019 Category: Endocrinology Source Type: research

Targeted deletion of Tcf7l2 in adipocytes promotes adipocyte hypertrophy and impaired glucose metabolism
ConclusionsTogether our studies support that TCF7L2 is a central transcriptional regulator of the adipocyte metabolic program by directly regulating the expression of genes involved in lipid and glucose metabolism. (Source: Molecular Metabolism)
Source: Molecular Metabolism - March 16, 2019 Category: Endocrinology Source Type: research

Discovering metabolic disease gene interactions by correlated effects on cellular morphology
ConclusionsThus, a morphometric approach in adipocytes can resolve multiple cellular mechanisms for metabolic disease loci; the platform enables mechanistic interrogation of the hundreds of metabolic disease loci whose function still remains unknown. (Source: Molecular Metabolism)
Source: Molecular Metabolism - March 14, 2019 Category: Endocrinology Source Type: research

Roux-en-Y gastric bypass surgery reprograms enterocyte triglyceride metabolism and postprandial secretion in rats
ConclusionOur results show that RYGB substantially reduces intestinal TG secretion and modifies enterocyte lipid absorption and handling in rats. These changes likely contribute to the improvements in the plasma TG profile observed after RYGB in humans. (Source: Molecular Metabolism)
Source: Molecular Metabolism - March 13, 2019 Category: Endocrinology Source Type: research

Liver-specific RORα deletion does not affect the metabolic susceptibility to western style diet feeding
ConclusionsOur data indicate that liver deletion of RORα does not have a pivotal role in the regulation of hepatic glucose and lipid metabolism on chow or western-style diet. (Source: Molecular Metabolism)
Source: Molecular Metabolism - March 9, 2019 Category: Endocrinology Source Type: research

Pirt deficiency has subtle female-specific effects on energy and glucose metabolism in mice
ConclusionWe here report subtle metabolic abnormalities in female, but not male, Pirt-/- mice. Future studies are required to tease out if metabolic stressors beyond dietary interventions, e.g. temperature fluctuations, are interacting with Pirt-signaling and metabolic control in a sex-specific fashion. (Source: Molecular Metabolism)
Source: Molecular Metabolism - March 9, 2019 Category: Endocrinology Source Type: research

A role for foregut tyrosine metabolism in glucose tolerance
ConclusionsWe provide proof-of-principle evidence for the existence of a novel postprandial circuit of glucose homeostasis dependent on nutritional tyrosine. DA and L-DOPA derived from nutritional tyrosine may serve to defend against hypoglycemia via inhibition of glucose-stimulated β-cell insulin secretion as proposed by the anti-incretin hypothesis.Graphical abstractLegend. Schematic of the proposed gut to pancreas blood glucose concentration regulatory circuit. Abbreviations used: TH, tyrosine hydroxylase; AADC, Aromatic l-amino acid decarboxylase; L-DOPA, L-3,4-dihydroxyphenylalanine; D2R, Dopamine receptor type 2...
Source: Molecular Metabolism - February 28, 2019 Category: Endocrinology Source Type: research

Perm1 regulates CaMKII activation and shapes skeletal muscle responses to endurance exercise training
ConclusionsOur findings identify Perm1 as a muscle-specific regulator of exercise-induced signaling and Perm1 levels as tuners of the skeletal muscle response to exercise. The decreased Perm1 levels in states of obesity or muscle disease suggest that Perm1 may link pathological states to inefficient exercise responses. (Source: Molecular Metabolism)
Source: Molecular Metabolism - February 28, 2019 Category: Endocrinology Source Type: research

Editorial Board, cover figure description and credits
Publication date: March 2019Source: Molecular Metabolism, Volume 21Author(s): (Source: Molecular Metabolism)
Source: Molecular Metabolism - February 28, 2019 Category: Endocrinology Source Type: research

Dysregulated transmethylation leading to hepatocellular carcinoma compromises redox homeostasis and glucose formation
ConclusionGlucose precursor flux away from glucose formation towards pathways that regulate redox status increase in the liver. Moreover, synthesis and scavenging of NAD+ are both impaired resulting in reduced concentrations. This metabolic program blunts an increase in methyl donor availability, however, biosynthetic pathways underlying HCC are activated. (Source: Molecular Metabolism)
Source: Molecular Metabolism - February 26, 2019 Category: Endocrinology Source Type: research

Tim-3 aggravates podocyte injury in diabetic nephropathy by promoting macrophage activation via the NF-κB/TNF-α pathway
ConclusionsThese results suggest that Tim-3 functions as a key regulator in renal inflammatory processes and serves as a potential therapeutic target for renal injury in DN. (Source: Molecular Metabolism)
Source: Molecular Metabolism - February 26, 2019 Category: Endocrinology Source Type: research

Dopamine neuronal protection in the mouse Substantia nigra by GHSR is independent of electric activity
ConclusionsTaken together, these observations unmasked a complex role of GHSR in dopamine neuronal protection independent on electric activity of these cells and revealed a crucial role for mitochondrial dynamics in some aspects of this process. (Source: Molecular Metabolism)
Source: Molecular Metabolism - February 22, 2019 Category: Endocrinology Source Type: research

Brown fat organogenesis and maintenance requires AKT1 and AKT2
ConclusionsAKT signaling is required in vivo for BAT development but dispensable for skeletal muscle development. AKT1 and AKT2 have both overlapping and distinct functions in BAT development with AKT2 being the most critical individual isoform. AKT1 and AKT2 also have distinct and complementary functions in BAT maintenance.Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - February 20, 2019 Category: Endocrinology Source Type: research

The Pseudokinase MLKL Regulates Hepatic Insulin Sensitivity Independently of Inflammation
ConclusionsThese findings reveal MLKL as a regulator of insulin sensitivity and suggest necroptotic regulators might be potential therapeutic targets for insulin resistance and T2D. (Source: Molecular Metabolism)
Source: Molecular Metabolism - February 20, 2019 Category: Endocrinology Source Type: research

Activation of hepatic estrogen receptor-α increases energy expenditure by stimulating the production of fibroblast growth factor 21 in female mice
ConclusionsIn female mice, E2 action on the hepatocyte ERα increases Fgf21 transcription and FGF21 production, thus promoting energy expenditure and partially decreasing fat accumulation. (Source: Molecular Metabolism)
Source: Molecular Metabolism - February 15, 2019 Category: Endocrinology Source Type: research

Functional peroxisomes are required for β-cell integrity in mice
ConclusionsOur data indicate that normal peroxisome metabolism in β-cells is crucial to preserve their structure and function.Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - February 9, 2019 Category: Endocrinology Source Type: research

Micromanaging aerobic respiration and glycolysis in cancer cells
ConclusionsMetabolism in cancer cells is influenced by driver mutations but is also regulated by posttranscriptional gene silencing. Understanding the nuanced regulation of gene expression in these cells and distinguishing rapid cellular responses from chronic adaptive mechanisms provides a basis for rational drug design and novel therapeutic strategies. (Source: Molecular Metabolism)
Source: Molecular Metabolism - February 6, 2019 Category: Endocrinology Source Type: research

Synbiotic-driven improvement of metabolic disturbances is associated with changes in the gut microbiome in diet-induced obese mice
ConclusionsOur results suggested that dietary intervention using the novel synbiotic can alleviate HFD-induced weight gain and restore gut microbial ecosystem homeostasis phylogenetically and functionally. (Source: Molecular Metabolism)
Source: Molecular Metabolism - February 5, 2019 Category: Endocrinology Source Type: research

The Brown Adipose Tissue Glucagon Receptor is Functional but Not Essential for Control of Energy Homeostasis in Mice
ConclusionsExogenous GCG increases oxygen consumption in mice, also evident both in liver and BAT explants ex vivo, through UCP1-independent, FGF21-dependent pathways. Nevertheless, GCGR signaling within BAT is not physiologically essential for control of body weight, whole body energy expenditure, glucose homeostasis, or the adaptive metabolic response to cold or prolonged exposure to an energy dense diet.Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - February 5, 2019 Category: Endocrinology Source Type: research

Pnpla3 Silencing with Antisense Oligonucleotides Ameliorates Nonalcoholic Steatohepatitis and Fibrosis in Pnpla3 I148M Knock-in Mice
ConclusionThis study provides the first evidence that a Pnpla3 ASO therapy can improve all features of NAFLD, including liver fibrosis, and suppress the expression of a strong innate genetic risk factor, Pnpla3 148M, which may open up a precision medicine approach in NASH. (Source: Molecular Metabolism)
Source: Molecular Metabolism - February 5, 2019 Category: Endocrinology Source Type: research

Repeated cold exposures protect a mouse model of Alzheimer's disease against cold-induced tau phosphorylation
ConclusionsOverall, BAT stimulation through RSCE improved metabolic deficits and completely blocked cold-induced tau hyperphosphorylation in the 3xTg-AD mouse model of AD neuropathology. These results suggest that improving thermogenesis could exert a therapeutic effect in AD. (Source: Molecular Metabolism)
Source: Molecular Metabolism - February 1, 2019 Category: Endocrinology Source Type: research

WWOX somatic ablation in skeletal muscles alters glucose metabolism
ConclusionsOur studies uncover an unforeseen role of the tumor suppressor WWOX in whole-body glucose homeostasis and highlight the intimate relationship between cancer progression and metabolic disorders, particularly obesity and type-2 diabetes.Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - February 1, 2019 Category: Endocrinology Source Type: research

Comprehensive and quantitative analysis of white and brown adipose tissue by shotgun lipidomics
ConclusionsThe here presented method facilitates reproducible systematic lipidomic profiling of AT and could be integrated with further –omics approaches used in (pre-) clinical research, in order to advance the understanding of the molecular metabolic dynamics involved in the pathogenesis of obesity-associated disorders.Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - January 31, 2019 Category: Endocrinology Source Type: research

Editorial Board, cover figure description and credits
Publication date: February 2019Source: Molecular Metabolism, Volume 20Author(s): (Source: Molecular Metabolism)
Source: Molecular Metabolism - January 29, 2019 Category: Endocrinology Source Type: research

Repeated cold exposures protect a mouse model of Alzheimer’s disease against cold-induced tau phosphorylation
ConclusionsOverall, BAT stimulation through RSCE improved metabolic deficits and completely blocked cold-induced tau hyperphosphorylation in the 3xTg-AD mouse model of AD neuropathology. These results suggest that improving thermogenesis could exert a therapeutic effect in AD. (Source: Molecular Metabolism)
Source: Molecular Metabolism - January 26, 2019 Category: Endocrinology Source Type: research

Silver nanoparticles inhibit beige fat function and promote adiposity
ConclusionsTaken together, these results revealed an unexpected role of AgNPs in promoting adiposity through the inhibition of beige adipocyte differentiation and functionality, possibly by disrupting ROS homeostasis and ERK phosphorylation. Future assessments on the health risk of AgNPs applications and their safe dosages are warranted. (Source: Molecular Metabolism)
Source: Molecular Metabolism - January 25, 2019 Category: Endocrinology Source Type: research

Transcriptional and Physiological Roles for STAT Proteins in Leptin Action
ConclusionsThus, STAT3 represents the unique STAT protein required for leptin action and STAT3 suffices to mediate important components of leptin action in the absence of other LepRb signals. (Source: Molecular Metabolism)
Source: Molecular Metabolism - January 25, 2019 Category: Endocrinology Source Type: research

Membrane Metallo-Endopeptidase (Neprilysin) Regulates Inflammatory Response and Insulin Signaling in White Preadipocytes
ConclusionMME is a novel regulator of the insulin receptor in adipose tissue. Given the clinical significance of both chronic inflammation and insulin sensitivity in metabolic disease, these results show a potentially new target to increase insulin sensitivity and decrease inflammatory susceptibility.Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - January 25, 2019 Category: Endocrinology Source Type: research

miR-132-3p is a positive regulator of alpha-cell mass and is downregulated in obese hyperglycemic mice
ConclusionsDownregulation of miR-132-3p in alpha-cells of obese diabetic mice may constitute a compensatory mechanism contributing to keep glucagon-producing cell number constant in diabetes. (Source: Molecular Metabolism)
Source: Molecular Metabolism - January 18, 2019 Category: Endocrinology Source Type: research

GDF15 acts synergistically with liraglutide but is not necessary for the weight loss induced by bariatric surgery in mice
ConclusionThese data suggest that while GDF15 does not play a role in the potent effects of VSG in mice there seems to be a potential therapeutic benefit of activating GFRAL and GLP-1R systems simultaneously. (Source: Molecular Metabolism)
Source: Molecular Metabolism - January 15, 2019 Category: Endocrinology Source Type: research

The translational regulator FMRP controls lipid and glucose metabolism in mice and humans
ConclusionsLoss of FMRP results in a widespread coordinated systemic response that notably involves upregulation of protein translation in the liver, increased utilization of lipids, and significant changes in metabolic homeostasis. Our study unravels metabolic phenotypes in FXS and further supports the importance of translational regulation in the homeostatic control of systemic metabolism.Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - January 15, 2019 Category: Endocrinology Source Type: research