Hypothalamic POMC or MC4R deficiency impairs counterregulatory responses to hypoglycemia in mice
ConclusionIn conclusion, hypothalamic Pomc as well as Mc4r, both of which are reduced in type 1 diabetic mice, are required for normal counterregulatory responses to hypoglycemia. Therefore, enhancing MC4R function may improve hypoglycemia counterregulation in diabetes.Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - November 21, 2018 Category: Endocrinology Source Type: research

Predicting and understanding the response to short-term intensive insulin therapy in people with early type 2 diabetes
Publication date: Available online 16 November 2018Source: Molecular MetabolismAuthor(s): Yury O. Nunez Lopez, Ravi Retnakaran, Bernard Zinman, Richard E. Pratley, Attila A. SeyhanAbstractObjectiveShort-term intensive insulin therapy (IIT) early in the course of type 2 diabetes acutely improves beta-cell function with long-lasting effects on glycemic control. However, conventional measures cannot determine which patients are better suited for IIT, and little is known about the molecular mechanisms determining response. Therefore, this study aimed to develop a model that could accurately predict the response to IIT and prov...
Source: Molecular Metabolism - November 17, 2018 Category: Endocrinology Source Type: research

Metformin Intervention Prevents Cardiac Dysfunction in a murine model of Adult Congenital Heart Disease
ConclusionsThis study reveals that early metabolic impairment reinforces heart dysfunction in ACHD predisposed individuals and diet or pharmacological interventions can be used to modulate heart function and attenuate heart failure. Our study suggests that interactions between genetic and metabolic disturbances ultimately lead to the clinical presentation of heart failure in patients with ACHD. Early manipulation of energy metabolism may be an important avenue for intervention in ACHD patients to prevent or delay onset of heart failure and secondary comorbidities. These interactions raise the prospect for a translational r...
Source: Molecular Metabolism - November 16, 2018 Category: Endocrinology Source Type: research

Regulation of Glucose Uptake and Inflammation Markers by FOXO1 and FOXO3 in Skeletal Muscle
Publication date: Available online 16 November 2018Source: Molecular MetabolismAuthor(s): Leonidas S. Lundell, Julie Massart, Ali Altıntaş, Anna Krook, Juleen R. ZierathAbstractObjectiveForkhead box class O (FOXO) transcription factors regulate whole body energy metabolism, skeletal muscle mass, and substrate switching. FOXO1 and FOXO3 are highly abundant transcription factors, but their precise role in skeletal muscle metabolism has not been fully elucidated.MethodTo elucidate the role of FOXO in skeletal muscle, dominant negative (dn) constructs for FOXO1 (FOXO1dn) or FOXO3 (FOXO3dn) were transfected by electroporation...
Source: Molecular Metabolism - November 16, 2018 Category: Endocrinology Source Type: research

Tannic acid, a new novel histone acetyltransferase inhibitor, prevents non-alcoholic fatty liver disease both in vivo and in vitro model
ConclusionsOur findings demonstrate that TA, a novel HATi, has potential application for the prevention of NAFLD.Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - November 11, 2018 Category: Endocrinology Source Type: research

The aromatic amino acid sensor GPR142 controls metabolism through balanced regulation of pancreatic and gut hormones
ConclusionsGPR142 functions as a sensor of aromatic amino acids, controlling GIP but also CCK and GLP-1 as well as insulin and glucagon in the pancreas. GPR142 agonists could have novel interesting potential in modifying metabolism through a balanced action of gut hormones as well as both insulin and glucagon. (Source: Molecular Metabolism)
Source: Molecular Metabolism - November 6, 2018 Category: Endocrinology Source Type: research

Fibroblast activation protein is dispensable for control of glucose homeostasis and body weight in mice
ConclusionAlthough pharmacological FAP inhibition improves glucose tolerance, the absence of a metabolic phenotype in Fap-/-mice suggest that endogenous FAP is dispensable for the regulation of murine glucose homeostasis and body weight. These findings highlight the importance of characterizing the specificity and actions of FAP inhibitors in different species and raise important questions about the feasibility of mouse models for targeting FAP as a treatment for diabetes and related metabolic disorders. (Source: Molecular Metabolism)
Source: Molecular Metabolism - November 6, 2018 Category: Endocrinology Source Type: research

CPT1C in the ventromedial nucleus of the hypothalamus is necessary for brown fat thermogenesis activation in obesity
ConclusionCPT1C is necessary for the activation of BAT thermogenesis driven by leptin, HF diet exposure, and AMPK inhibition within the VMH. This study underscores the importance of CPT1C in the activation of BAT thermogenesis to counteract diet-induced obesity. (Source: Molecular Metabolism)
Source: Molecular Metabolism - November 3, 2018 Category: Endocrinology Source Type: research

SGLT1 in pancreatic α cells regulates glucagon secretion in mice, possibly explaining the distinct effects of SGLT2 inhibitors on plasma glucagon levels
ConclusionsThese data suggested that a novel mechanism regulated glucagon secretion through SGLT1 in α cells. This finding possibly explained the distinct effects of dapagliflozin and canagliflozin on plasma glucagon levels in mice. (Source: Molecular Metabolism)
Source: Molecular Metabolism - October 27, 2018 Category: Endocrinology Source Type: research

An in vivo screen for neuronal genes involved in obesity identifies diacylglycerol kinase as a regulator of insulin secretion
ConclusionAltogether, we have identified several genes that act within the CNS to regulate energy homeostasis. One of these, Dgk, acts within the insulin-producing cells to regulate the secretion of dILPs and energy homeostasis in Drosophila.Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - October 25, 2018 Category: Endocrinology Source Type: research

The Insulin like growth factor and binding protein family: novel therapeutic targets in obesity & diabetes
Publication date: Available online 24 October 2018Source: Molecular MetabolismAuthor(s): Natalie J. Haywood, Thomas A. Slater, Connor J. Matthews, Stephen B. WheatcroftAbstractBackgroundRecent changes in nutrition and lifestyle have provoked an unprecedented increase in the prevalence of obesity and metabolic disorders. Recognition of the adverse effects on health has prompted intense efforts to understand the molecular determinants of insulin sensitivity and dysglycemia. In many respects, actions of insulin-like growth factors (IGFs) mirror those of insulin in metabolic regulation. Unlike insulin, however, the bioactivity...
Source: Molecular Metabolism - October 25, 2018 Category: Endocrinology Source Type: research

Diet-dependent function of the extracellular matrix proteoglycan Lumican in obesity and glucose homeostasis
ConclusionsThese data indicate that Lumican may represent a functional link between the extracellular matrix, glucose homeostasis, and features of the metabolic syndrome. (Source: Molecular Metabolism)
Source: Molecular Metabolism - October 24, 2018 Category: Endocrinology Source Type: research

An In Vivo Screen for Neuronal Genes Involved in Obesity Identifies Diacylglycerol Kinase as a Regulator of Insulin Secretion
ConclusionAltogether, we have identified several genes that act within the CNS to regulate energy homeostasis. One of these, Dgk, acts within the insulin-producing cells to regulate the secretion of dILPs and energy homeostasis in Drosophila.Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - October 21, 2018 Category: Endocrinology Source Type: research

Moderate weight loss attenuates chronic endoplasmic reticulum stress and mitochondrial dysfunction in human obesity
ConclusionsOur data provide evidence that moderate weight loss attenuates systemic inflammation and IR and promotes the amelioration of ER stress and mitochondrial dysfunction, increasing the expression of chaperones, SIRT1 and antioxidant GPX1.Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - October 21, 2018 Category: Endocrinology Source Type: research

“Let's Stay Together”; GIP and GLP-1 dual agonism in the treatment of metabolic disease
Publication date: Available online 12 October 2018Source: Molecular MetabolismAuthor(s): Richard D. DiMarchi (Source: Molecular Metabolism)
Source: Molecular Metabolism - October 19, 2018 Category: Endocrinology Source Type: research

Editorial Board, cover figure description and credits
Publication date: November 2018Source: Molecular Metabolism, Volume 17Author(s): (Source: Molecular Metabolism)
Source: Molecular Metabolism - October 18, 2018 Category: Endocrinology Source Type: research

“Let’s Stay Together”; GIP and GLP-1 Dual Agonism in the Treatment of Metabolic Disease
Publication date: Available online 12 October 2018Source: Molecular MetabolismAuthor(s): Richard D. DiMarchi (Source: Molecular Metabolism)
Source: Molecular Metabolism - October 13, 2018 Category: Endocrinology Source Type: research

Control of hepatic gluconeogenesis by Argonaute2
ConclusionsThese data illustrate a central role for Ago2 in the adaptive response of the liver to fasting. Ago2 mediates the suppression of AMPKα1 by miR-148a, thereby identifying a regulatory link between non-coding RNAs and a key stress regulator in the hepatocyte. (Source: Molecular Metabolism)
Source: Molecular Metabolism - October 9, 2018 Category: Endocrinology Source Type: research

Phenotyping of circulating extracellular vesicles (EVs) in obesity identifies large EVs as functional conveyors of Macrophage Migration Inhibitory Factor
ConclusionOur results emphasize the importance of reconsidering MIF-metabolic actions with regard to its MV-associated form and opening new EV-based strategies for therapeutic MIF approaches.Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - October 9, 2018 Category: Endocrinology Source Type: research

TRPV1 Neurons Regulate β-Cell Function in a Sex-Dependent Manner
ConclusionCollectively, these findings suggest that TRPV1 neurons regulate glucose homeostasis, at least partly, through direct modulation of glucose-induced insulin secretion and that this regulation operates in a sex-dependent manner. (Source: Molecular Metabolism)
Source: Molecular Metabolism - October 7, 2018 Category: Endocrinology Source Type: research

Glucose tolerance and insulin sensitivity define adipocyte transcriptional programs in human obesity
Publication date: Available online 19 September 2018Source: Molecular MetabolismAuthor(s): R. Gerlini, L. Berti, J. Darr, M. Lassi, S. Brandmaier, L. Fritsche, F. Scheid, A. Böhm, A. Königsrainer, H. Grallert, H.U. Häring, M. Hrabě de Angelis, H. Staiger, R. TeperinoAbstractObjectivesAlthough debated, metabolic health characterizes 10–25% of obese individuals and reduces risk of developing life-threatening co-morbidities. Adipose tissue is a recognized endocrine organ important for the maintenance of whole-body metabolic health. Adipocyte transcriptional signatures of healthy and unhealthy obesity are...
Source: Molecular Metabolism - October 5, 2018 Category: Endocrinology Source Type: research

Ghrelin transport across the blood–brain barrier can occur independently of the growth hormone secretagogue receptor
ConclusionsThe data presented here suggest that ghrelin transport can occur independently of the GHSR, and ghrelin uptake varies regionally throughout the brain. These findings better our understanding of the gut-brain communication and may lead to new understandings of ghrelin physiology. (Source: Molecular Metabolism)
Source: Molecular Metabolism - October 5, 2018 Category: Endocrinology Source Type: research

Switching obese mothers to a healthy diet improves fetal hypoxemia, hepatic metabolites, and lipotoxicity in non-human primates
ConclusionsOur data provide new metabolic evidence that, in addition to fetal hepatic steatosis, maternal WSD creates fetal hypoxemia and increases utilization of AAs for energy production and early activation of gluconeogenic pathways in the fetal liver. When combined with hyperlipidemia and limited antioxidant activity, the fetus suffers from hepatic oxidative stress and altered intracellular metabolism which can be improved with maternal diet intervention. Our data reinforce the concept that multiple “first hits” occur in the fetus prior to development of obesity and demonstrate new biomarkers with potential...
Source: Molecular Metabolism - October 5, 2018 Category: Endocrinology Source Type: research

Editorial Board, cover figure description and credits
Publication date: October 2018Source: Molecular Metabolism, Volume 16Author(s): (Source: Molecular Metabolism)
Source: Molecular Metabolism - October 5, 2018 Category: Endocrinology Source Type: research

LY3298176, A Novel Dual GIP And GLP-1 Receptor Agonist For The Treatment Of Type 2 Diabetes Mellitus: From Discovery To Clinical Proof Of Concept
ConclusionsBased on these results, the pharmacology of LY3298176 translates from preclinical to clinical studies. LY3298176 has the potential to deliver clinically meaningful improvement in glycaemic control and body weight. The data warrant further clinical evaluation of LY3298176 for the treatment of T2DM and potentially obesity. (Source: Molecular Metabolism)
Source: Molecular Metabolism - October 5, 2018 Category: Endocrinology Source Type: research

Overexpression of Melanocortin 2 Receptor Accessory Protein 2 (MRAP2) in adult paraventricular MC4R neurons regulates energy intake and expenditure
ConclusionsOur data indicate a site-specific role for MRAP2 in PVN MC4R-expressing neurons in potentiating MC4R neuronal activation at baseline conditions in the regulation of food intake and energy expenditure. (Source: Molecular Metabolism)
Source: Molecular Metabolism - October 5, 2018 Category: Endocrinology Source Type: research

N-terminal transactivation function, AF-1, of estrogen receptor alpha controls obesity through enhancement of energy expenditure
ConclusionsThese results suggest that the activation of ERα AF-1 prevents fat accumulation. The prevention of obesity through AF-1 is mediated by induction of energy expenditure rather than ERα AF-1 functionality of lipid metabolism gene regulation in fat tissues. (Source: Molecular Metabolism)
Source: Molecular Metabolism - September 21, 2018 Category: Endocrinology Source Type: research

Insulin Receptor-Mediated Signaling Regulates Pluripotency Markers and Lineage Differentiation
ConclusionWe report, for the first time to our knowledge, the phosphoproteome of insulin, IGF1, and LIF stimulation in mouse iPSCs to reveal the importance of insulin receptor signaling for the maintenance of pluripotency and lineage determination.Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - September 20, 2018 Category: Endocrinology Source Type: research

Compensatory Mechanisms for Methylglyoxal Detoxification in Experimental & Clinical Diabetes
CONCLUSIONSThese data suggest that in the absence of GLO1, AKR can effectively compensate to prevent the accumulation of MG. The combination of metabolic, enzymatic, and genetic factors, therefore, may provide a better means of identifying patients who are at risk for the development of late complications caused by elevated levels of MG. (Source: Molecular Metabolism)
Source: Molecular Metabolism - September 20, 2018 Category: Endocrinology Source Type: research

Obesityglucose Tolerance And Insulin Sensitivity Define Adipocyte Transcriptional Programs In Human Obesity
ConclusionSOur study showed that glucose intolerance and insulin resistance co-operate to remodel adipocyte transcriptome. We also identified the Nuclear Export Mediator Factor (NEMF) and the Ectoderm-Neural Cortex 1 (ENC1) as novel potential targets in the management of metabolic health in human obesity.Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - September 20, 2018 Category: Endocrinology Source Type: research

Endocannabinoid and nitric oxide systems of the hypothalamic paraventricular nucleus mediate effects of NPY on energy expenditure
ConclusionThus, within the PVN, NPY stimulates the release of endocannabinoids and NO via Ca2+-influx from the endoplasmic reticulum. Both transmitter systems appear to have unique roles in the mediation of the NPY-induced regulation of energy homeostasis, suggesting that NPY regulates food intake, energy expenditure, and locomotor activity through different neuronal networks of this nucleus.Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - September 19, 2018 Category: Endocrinology Source Type: research

Activation of Estrogen Receptor Alpha Induces Beiging of Adipocytes
ConclusionOur results demonstrate for the first time that selective-activation of ERα in adipocytes increases markers of beiging and this is likely through induction of AMPK and ATGL-mediated lipolysis providing FFAs as a fuel to activate UCP-1. (Source: Molecular Metabolism)
Source: Molecular Metabolism - September 16, 2018 Category: Endocrinology Source Type: research

Neuronatin deletion causes postnatal growth restriction and adult obesity in 129S2/Sv mice
ConclusionsThe imprinted gene Nnat plays a key role in postnatal growth, adult energy homeostasis, and the pathogenesis of obesity via catch up growth effects, but this role is dependent upon genetic background. (Source: Molecular Metabolism)
Source: Molecular Metabolism - September 15, 2018 Category: Endocrinology Source Type: research

Cellular and synaptic reorganization of arcuate NPY/AgRP and POMC neurons after Exercise
ConclusionsTogether, these data support a rapid reorganization of synaptic inputs and biophysical properties in response to exercise, which may facilitate adaptations to altered energy balance and glucose metabolism. (Source: Molecular Metabolism)
Source: Molecular Metabolism - September 13, 2018 Category: Endocrinology Source Type: research

Hepatic leptin receptor expression can partially compensate for IL-6Rα deficiency in DEN-induced hepatocellular carcinoma
ConclusionsOur findings reveal a compensatory role for hepatic LEPR in HCC development of IL-6Rα-deficient mice and suggest hepatocyte-specific leptin signaling as promoter of HCC under obese conditions.Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - September 10, 2018 Category: Endocrinology Source Type: research

Hepatic leptin receptor expression can partially compensate for IL-6Rα deficiency in DEN-induced hepatocellular carcinoma
ConclusionsOur findings reveal a compensatory role for hepatic LEPR in HCC development of IL-6Rα-deficient mice and suggest hepatocyte-specific leptin signaling as promoter of HCC under obese conditions.Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - September 5, 2018 Category: Endocrinology Source Type: research

Quantitative mass spectrometry for human melanocortin peptides in vitro and in vivo suggests prominent roles for β-MSH and desacetyl α-MSH in energy homeostasis
Publication date: Available online 21 August 2018Source: Molecular MetabolismAuthor(s): Peter Kirwan, Richard G. Kay, Bas Brouwers, Vicente Herranz-Pérez, Magdalena Jura, Pierre Larraufie, Julie Jerber, Jason Pembroke, Theresa Bartels, Anne White, Fiona M. Gribble, Frank Reimann, I. Sadaf Farooqi, Stephen O'Rahilly, Florian T. MerkleAbstractObjectiveThe lack of pro-opiomelanocortin (POMC)-derived melanocortin peptides results in hypoadrenalism and severe obesity in both humans and rodents that is treatable with synthetic melanocortins. However, there are significant differences in POMC processing between humans and ...
Source: Molecular Metabolism - August 28, 2018 Category: Endocrinology Source Type: research

T1R2 receptor-mediated glucose sensing in the upper intestine potentiates glucose absorption through activation of local regulatory pathways
ConclusionsOur studies demonstrate that STRs have evolved to modulate glucose absorption via the regulation of its transport and to prevent the development of exacerbated hyperglycemia due to the ingestion of high levels of sugars. (Source: Molecular Metabolism)
Source: Molecular Metabolism - August 28, 2018 Category: Endocrinology Source Type: research

Periodized low protein-high carbohydrate diet confers potent, but transient, metabolic improvements
ConclusionThese results suggest that pLPHC may be a viable strategy to promote human health but also highlight the transient nature of the benefits and that the interaction with other lifestyle-interventions such as exercise training warrants consideration.Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - August 28, 2018 Category: Endocrinology Source Type: research

Quantitative mass spectrometry for human melanocortin peptides in vitro and in vivo suggests prominent roles for β-MSH and desacetyl α-MSH in energy homeostasis
Publication date: Available online 21 August 2018Source: Molecular MetabolismAuthor(s): Peter Kirwan, Richard G. Kay, Bas Brouwers, Vicente Herranz-Pérez, Magdalena Jura, Pierre Larraufie, Julie Jerber, Jason Pembroke, Theresa Bartels, Anne White, Fiona M. Gribble, Frank Reimann, I. Sadaf Farooqi, Stephen O’Rahilly, Florian T. MerkleAbstractObjectiveThe lack of pro-opiomelanocortin (POMC)-derived melanocortin peptides results in hypoadrenalism and severe obesity in both humans and rodents that is treatable with synthetic melanocortins. However, there are significant differences in POMC processing between human...
Source: Molecular Metabolism - August 21, 2018 Category: Endocrinology Source Type: research

Deletion of the glucagon receptor gene before and after experimental diabetes reveals differential protection from hyperglycemia
ConclusionsThese findings demonstrate that the effects of glucagon to mitigate diabetic hyperglycemia are not through acute signaling but require compensations that take weeks to develop. (Source: Molecular Metabolism)
Source: Molecular Metabolism - August 21, 2018 Category: Endocrinology Source Type: research

Sex dependent impact of gestational stress on predisposition to eating disorders and metabolic disease
ConclusionsOur results show that maternal stress may have variable and even opposing effects on ED risk, depending on the ED and the sex of the offspring. (Source: Molecular Metabolism)
Source: Molecular Metabolism - August 21, 2018 Category: Endocrinology Source Type: research

Distinct lipid droplet characteristics and distribution unmask the apparent contradiction of the athlete’s paradox
ConclusionsOur findings provide a physiological explanation for the athlete’s paradox and reveal LD morphology and distribution as a major determinant of skeletal muscle insulin sensitivity. (Source: Molecular Metabolism)
Source: Molecular Metabolism - August 18, 2018 Category: Endocrinology Source Type: research

A PDX1-ATF transcriptional complex governs β cell survival during stress
ConclusionsOur results identify a novel PDX1 stress inducible complex (es) that regulates expression of stress and apoptosis genes to govern β cell survival.Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - August 17, 2018 Category: Endocrinology Source Type: research

L-Alanine Activates Hepatic Amp-Activated Protein Kinase And Modulates Systemic Glucose Metabolism
ConclusionsAla may serve as a distinct amino acid energy sensor, providing a positive signal to activate the beneficial AMPK signaling pathway.Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - August 15, 2018 Category: Endocrinology Source Type: research

Molecular Reductions in Glucokinase Activity Increase Counter-regulatory Responses to Hypoglycemia in Mice and Humans with Diabetes
ConclusionsOur data suggest that glucokinase in brain and other non β-cell peripheral hypoglycemia sensors is important in glucose homeostasis, allowing the body to detect and respond to a falling blood glucose.Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - August 13, 2018 Category: Endocrinology Source Type: research

d-Alanine Activates Hepatic AMP-Activated Protein Kinase and Modulates Systemic Glucose Metabolism
ConclusionsAla may serve as a distinct amino acid energy sensor, providing a positive signal to activate the beneficial AMPK signaling pathway.Graphical abstract (Source: Molecular Metabolism)
Source: Molecular Metabolism - August 11, 2018 Category: Endocrinology Source Type: research

microRNA-205-5p is a Modulator of Insulin Sensitivity that Inhibits FOXO Function
ConclusionsThese findings reveal a homeostatic miRNA loop regulating insulin signaling, with potential implications for in vivo glucose metabolism. (Source: Molecular Metabolism)
Source: Molecular Metabolism - August 11, 2018 Category: Endocrinology Source Type: research

AMPK activation negatively regulates GDAP1, which influences metabolic processes and circadian gene expression in skeletal muscle
ConclusionWe describe a role for GDAP1 in regulating mitochondrial proteins, circadian genes, and metabolic flux in skeletal muscle. Collectively, our results implicate GDAP1 in the circadian control of metabolism. (Source: Molecular Metabolism)
Source: Molecular Metabolism - August 7, 2018 Category: Endocrinology Source Type: research

Intestinal Bitter Taste Receptor Activation Alters Hormone Secretion And Imparts Metabolic Benefits
ConclusionsActivation of Tas2r108 in the gut results in a remodeling of enteroendocrine hormone release and bile acid metabolism that ameliorates multiple features of metabolic syndrome. Targeting extraoral bitter taste receptors may be useful in metabolic disease. (Source: Molecular Metabolism)
Source: Molecular Metabolism - August 4, 2018 Category: Endocrinology Source Type: research