Abstract：
OBJECTIVES:Melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus (LH) regulate food intake and body weight, glucose metabolism and convey the reward value of sucrose. In this report, we set out to establish the respective roles of MCH and conventional neurotransmitters in these neurons. METHODS:MCH neurons were profiled using Cre-dependent molecular profiling technologies (vTRAP). MCHCre mice crossed to Vglut2fl/flmice or to DTRfl/flwere used to identify the role of glutamate in MCH neurons. We assessed metabolic parameters such as body composition, glucose tolerance, or sucrose preference. RESULTS:We found that nearly all MCH neurons in the LH are glutamatergic and that a loss of glutamatergic signaling from MCH neurons from a glutamate transporter (VGlut2) knockout leads to a reduced weight, hypophagia and hyperkinetic behavior with improved glucose tolerance and a loss of sucrose preference. These effects are indistinguishable from those seen after ablation of MCH neurons. These findings are in contrast to those seen in mice with a knockout of the MCH neuropeptide, which show normal glucose preference and do not have improved glucose tolerance. CONCLUSIONS:Overall, these data show that the vast majority of MCH neurons are glutamatergic, and that glutamate and MCH signaling mediate partially overlapping functions by these neurons, presumably by activating partially overlapping postsynaptic populations. The diverse functional effects of MCH neurons are thus mediated by a composite of glutamate and MCH signaling.
journal_name
Mol Metabjournal_title
Molecular metabolismauthors
Schneeberger M,Tan K,Nectow AR,Parolari L,Caglar C,Azevedo E,Li Z,Domingos A,Friedman JMdoi
10.1016/j.molmet.2018.05.001subject
Has Abstractpub_date
2018-07-01 00:00:00pages
83-89issn
2212-8778pii
S2212-8778(18)30364-8journal_volume
13pub_type
杂志文章abstract：:Decreased β-cell mass reflects a shift from quiescence/proliferation into apoptosis, it plays a crucial role in the pathophysiology of diabetes. A major attempt to restore β-cell mass and normoglycemia is to improve β-cell survival. Here we show that switching off the Fas pathway using Fas apoptotic inhibitory protein...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2012.08.006
更新日期：2012-08-17 00:00:00
abstract：BACKGROUND:While additional research is needed, a number of large epidemiological studies show an association between circadian disruption and metabolic disorders. Specifically, obesity, insulin resistance, cardiovascular disease, and other signs of metabolic syndrome all have been linked to circadian disruption in hum...
journal_title：Molecular metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.molmet.2015.12.006
更新日期：2016-01-14 00:00:00
abstract：OBJECTIVE:Glucagon-like peptide 1 (GLP-1) enhances insulin secretion and protects β-cell mass. Diabetes therapies targeting the GLP-1 receptor (GLP-1R), expressed in numerous tissues, have diminished dose-response in patients with type 2 diabetes compared with healthy human controls. The aim of this study was to determ...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2015.01.010
更新日期：2015-02-03 00:00:00
abstract：BACKGROUND:Poly-ADP-ribose polymerases (PARPs) are key mediators of cellular stress response. They are intimately linked to cellular metabolism through the consumption of NAD+. PARP1/ARTD1 in the nucleus is the major NAD+ consuming activity and plays a key role in maintaining genomic integrity. SCOPE OF REVIEW:In this...
journal_title：Molecular metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.molmet.2020.01.014
更新日期：2020-08-01 00:00:00
abstract：OBJECTIVE:Leptin (Lep) plays a crucial role in controlling food intake and energy expenditure. Defective Lep/LepRb-signaling leads to fat accumulation, massive obesity, and the development of diabetes. We serendipitously noticed spontaneous development of obesity similar to LepR-deficient (db/db) mice in offspring from...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2019.04.010
更新日期：2019-07-01 00:00:00
abstract：BACKGROUND:Non-alcoholic steatohepatitis (NASH) is a spectrum of histological liver pathologies ranging from hepatocyte fat accumulation, hepatocellular ballooning, lobular inflammation, and pericellular fibrosis. Based on early investigations, it was discovered that visceral fat accumulation, hepatic insulin resistanc...
journal_title：Molecular metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.molmet.2020.101153
更新日期：2020-12-23 00:00:00
abstract：OBJECTIVE:Obesity is strongly linked to genes regulating neuronal signaling and function, implicating the central nervous system in the maintenance of body weight and energy metabolism. Genome-wide association studies identified significant associations between body mass index (BMI) and multiple loci near Cell adhesion...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2017.11.010
更新日期：2018-02-01 00:00:00
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journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2019.08.007
更新日期：2019-11-01 00:00:00
abstract：OBJECTIVE:α-cells are the second most prominent cell type in pancreatic islets and are responsible for producing glucagon to increase plasma glucose levels in times of fasting. α-cell dysfunction and inappropriate glucagon secretion occur in both type 1 and type 2 diabetes. Thus, there is growing interest in studying b...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2017.01.003
更新日期：2017-01-12 00:00:00
abstract：:Genetic variation in FFAR1 modulates insulin secretion dependent on non-esterified fatty acid (NEFA) concentrations. We previously demonstrated lower insulin secretion in minor allele carriers of PPARG Pro12Ala in high-NEFA environment, but the mode of action could not been revealed. We tested if this effect is mediat...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2014.07.001
更新日期：2014-07-07 00:00:00
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journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2020.101052
更新日期：2020-11-01 00:00:00
abstract：:Oxyntomodulin (OXM) is a peptide hormone released from the gut in post-prandial state that activates both the glucagon-like peptide-1 receptor (GLP1R) and the glucagon receptor (GCGR) resulting in superior body weight lowering to selective GLP1R agonists. OXM reduces food intake and increases energy expenditure in hum...
journal_title：Molecular metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.molmet.2013.12.001
更新日期：2013-12-14 00:00:00
abstract：BACKGROUND:The TP53 gene is one of the most commonly inactivated tumor suppressors in human cancers. p53 functions during cancer progression have been linked to a variety of transcriptional and non-transcriptional activities that lead to the tight control of cell proliferation, senescence, DNA repair, and cell death. H...
journal_title：Molecular metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.molmet.2019.10.002
更新日期：2020-03-01 00:00:00
abstract：:The contribution of mitochondrial dysfunction to insulin resistance is a contentious issue in metabolic research. Recent evidence implicates mitochondrial dysfunction as contributing to multiple forms of insulin resistance. However, some models of mitochondrial dysfunction fail to induce insulin resistance, suggesting...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2014.02.001
更新日期：2014-03-12 00:00:00
abstract：:11β-Hydroxysteroid dehydrogenase-1 (11β-HSD1) plays a key role in glucocorticoid receptor (GR) activation. Besides, it metabolizes some oxysterols and bile acids (BAs). The GR regulates BA homeostasis; however, the impact of impaired 11β-HSD1 activity remained unknown. We profiled plasma and liver BAs in liver-specifi...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2014.04.008
更新日期：2014-05-02 00:00:00
abstract：BACKGROUND:Evidence hints at the ability of β-cells to emerge from non-β-cells upon genetic or pharmacological interventions. However, their quantitative contributions to the process of autonomous β-cell regeneration without genetic or pharmacological manipulations remain to be determined. METHODS & RESULTS:Using PANI...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2016.05.001
更新日期：2016-05-10 00:00:00
abstract：OBJECTIVE:The glycoprotein hormone erythropoietin (EPO) is required for erythropoiesis, and the kidney is the primary site of adult EPO synthesis. Limited evidence has suggested that EPO could be detectable in the brain under certain conditions, but it remains unknown if the brain might have its own EPO system for biol...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2019.12.001
更新日期：2020-02-01 00:00:00
abstract：OBJECTIVE:Estrogen receptor-α (ERα) is a nuclear receptor family member thought to substantially contribute to the metabolic regulation of skeletal muscle. However, previous mouse models utilized to assess the necessity of ERα signaling in skeletal muscle were confounded by altered developmental programming and/or infl...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2019.12.010
更新日期：2020-04-01 00:00:00
abstract：OBJECTIVES:Preferential damage to fast, glycolytic myofibers is common in many muscle-wasting diseases, including Duchenne muscular dystrophy (DMD). Promoting an oxidative phenotype could protect muscles from damage and ameliorate the dystrophic pathology with therapeutic relevance, but developing efficacious strategie...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2020.101157
更新日期：2020-12-24 00:00:00
abstract：OBJECTIVE:Understanding the mechanisms underlying the remarkable beneficial effects of gastric bypass surgery is important for the development of non-surgical therapies or less invasive surgeries in the fight against obesity and metabolic disease. Although the intestinal L-cell hormones glucagon-like peptide-1 (GLP-1) ...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2019.05.004
更新日期：2019-07-01 00:00:00
abstract：OBJECTIVE:Despite the large body of work describing the tumor suppressor functions of Phosphatase and tensin homologue deleted on chromosome ten (PTEN), its roles in adipose homeostasis of adult animals are not yet fully understood. Here, we sought to determine the role of PTEN in whole-body adipose homeostasis. METHO...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2019.09.008
更新日期：2019-12-01 00:00:00
abstract：OBJECTIVE:Functional investigation of novel gene/protein targets associated with adipocyte differentiation or function heavily relies on efficient and accessible tools to manipulate gene expression in adipocytes in vitro. Recent advances in gene-editing technologies such as CRISPR-Cas9 have not only eased gene editing ...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2017.07.001
更新日期：2017-10-01 00:00:00
abstract：BACKGROUND:Modern lifestyles, especially high-caloric intake and physical inactivity, contribute to the increased prevalence of non-alcoholic fatty liver disease (NAFLD), which becomes a significant health problem worldwide. Lifestyle changes, however, affect not only parental generation, but also their offspring, rein...
journal_title：Molecular metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.molmet.2019.11.015
更新日期：2020-02-01 00:00:00
abstract：BACKGROUND:Diabetes is one of the greatest public health challenges worldwide, and we still lack complementary approaches to significantly enhance the efficacy of preventive and therapeutic approaches. Genetic and environmental factors are the culprits involved in diabetes risk. Evidence from the last decade has highli...
journal_title：Molecular metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.molmet.2020.101041
更新日期：2020-11-01 00:00:00
abstract：OBJECTIVE:Brown adipose tissue (BAT) thermogenesis depends on the mobilization and oxidation of fatty acids from intracellular lipid droplets (LD) within brown adipocytes (BAs); however, the identity and function of LD proteins that control BAT lipolysis remain incomplete. Proteomic analysis of mouse BAT subcellular fr...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2017.10.014
更新日期：2018-01-01 00:00:00
abstract：BACKGROUND:Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among reproductive age women. Although its cardinal manifestations include hyperandrogenism, oligo/anovulation, and/or polycystic ovarian morphology, PCOS women often display also notable metabolic comorbidities. An array of pathogenic mechan...
journal_title：Molecular metabolism
pub_type： 杂志文章,评审
doi：10.1016/j.molmet.2020.01.001
更新日期：2020-05-01 00:00:00
abstract：OBJECTIVE:Glucagon is a hormone with metabolic actions that maintains normoglycemia during the fasting state. Strategies enabling either inhibition or activation of glucagon receptor (Gcgr) signaling are being explored for the treatment of diabetes or obesity. However, the cardiovascular consequences of manipulating gl...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2014.11.005
更新日期：2014-11-29 00:00:00
abstract：:Melanocortins and their receptors are critical components of energy homeostasis and the paraventricular nucleus of the hypothalamus (PVH) is an important site of melanocortin action. Although best known for its role in osmoregulation, arginine vasopressin (AVP) has been implicated in feeding and is robustly expressed ...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2013.12.006
更新日期：2014-01-08 00:00:00
abstract：OBJECTIVE:Surplus dietary fat cannot be converted into other macronutrient forms or excreted, so has to be stored or oxidized. Healthy mammals store excess energy in the form of triacylgycerol (TAG) in lipid droplets within adipocytes rather than oxidizing it, and thus ultimately gain weight. The 'overflow hypothesis' ...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2018.05.006
更新日期：2018-07-01 00:00:00
abstract：OBJECTIVES:We quantified the effect of environmental temperature on mouse energy homeostasis and body temperature. METHODS:The effect of environmental temperature (4-33 °C) on body temperature, energy expenditure, physical activity, and food intake in various mice (chow diet, high-fat diet, Brs3 (-/y) , lipodystrophic...
journal_title：Molecular metabolism
pub_type： 杂志文章
doi：10.1016/j.molmet.2015.03.001
更新日期：2015-03-10 00:00:00
