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 fractions identified vacuolar protein sorting 13C (VPS13C) as a novel LD protein. The aim of this work was to investigate the role of VPS13C on BA LDs. METHODS:Biochemical fractionation and high resolution confocal and immuno-transmission electron microscopy (TEM) were used to determine the subcellular distribution of VPS13C in mouse BAT, white adipose tissue, and BA cell culture. Lentivirus-delivered shRNA was used to determine the role of VPS13C in regulating lipolysis and gene expression in cultured BA cells. RESULTS:We found that VPS13C is highly expressed in mouse BAT where it is targeted to multilocular LDs in a subspherical subdomain. In inguinal white adipocytes, VPS13C was mainly observed on small LDs and β3-adrenergic stimulation increased VPS13C in this depot. Silencing of VPS13C in cultured BAs decreased LD size and triglyceride content, increased basal free fatty acid release, augmented the expression of thermogenic genes, and enhanced the lipolytic potency and efficacy of isoproterenol. Mechanistically, we found that BA lipolysis required activation of adipose tissue triglyceride lipase (ATGL) and that loss of VPS13C greatly increased the association of ATGL to LDs. CONCLUSIONS:VPS13C is present on BA LDs where is targeted to a distinct subdomain. VPS13C limits the access of ATGL to LD and loss of VPS13C elevates lipolysis and promotes oxidative gene expression.
journal_name
Mol Metabjournal_title
Molecular metabolismauthors
Ramseyer VD,Kimler VA,Granneman JGdoi
10.1016/j.molmet.2017.10.014subject
Has Abstractpub_date
2018-01-01 00:00:00pages
57-70issn
2212-8778pii
S2212-8778(17)30665-8journal_volume
7pub_type
杂志文章abstract:OBJECTIVE:Dedifferentiation of pancreatic β-cells may reduce islet function in type 2 diabetes (T2D). However, the prevalence, plasticity and functional consequences of this cellular state remain unknown. METHODS:We employed single-cell RNAseq to detail the maturation program of α- and β-cells during human ontogeny. W...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2020.101057
更新日期:2020-12-01 00:00:00
abstract:OBJECTIVE:Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin receptor kinase B (TrkB), play a paramount role in the central regulation of energy balance. Despite the substantial body of genetic evidence implicating BDNF- or TrkB-deficiency in human obesity, the critical brain region(s) contributing ...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2015.08.002
更新日期:2015-08-18 00:00:00
abstract:OBJECTIVE:Recent reports have implicated the p53 tumor suppressor in the regulation of lipid metabolism. We hypothesized that the pharmacological activation of p53 with low-dose doxorubicin, which is widely used to treat several types of cancer, may have beneficial effects on nonalcoholic fatty liver disease (NAFLD) an...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2017.12.005
更新日期:2018-02-01 00:00:00
abstract:OBJECTIVE:Skeletal muscle AMP-activated protein kinase (AMPK) is important for regulating glucose homeostasis, mitochondrial content and exercise capacity. R419 is a mitochondrial complex-I inhibitor that has recently been shown to acutely activate AMPK in myotubes. Our main objective was to examine whether R419 treatm...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2015.06.002
更新日期:2015-06-15 00:00:00
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 n...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2018.05.001
更新日期:2018-07-01 00:00:00
abstract:OBJECTIVES:The skin is the largest sensory organ of the human body and plays a fundamental role in regulating body temperature. However, adaptive alterations in skin functions and morphology have only vaguely been associated with physiological responses to cold stress or sensation of ambient temperatures. We previously...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2020.101144
更新日期:2020-12-18 00:00:00
abstract:BACKGROUND:The availability of human pancreatic islets with characteristics closely resembling those present in vivo is instrumental for ex vivo studies in diabetes research. SCOPE OF REVIEW:In this review we propose metabolically phenotyped surgical patients as a novel source of pancreatic tissue for islet research. ...
journal_title:Molecular metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.molmet.2019.06.006
更新日期:2019-09-01 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:OBJECTIVE:Previous work has suggested that white adipocytes may also show a mammary luminal secretory cell phenotype during lactation. The capacity of brown and beige/brite adipocytes to display a mammary cell phenotype and the levels at which they demonstrate such phenotypes in vivo is currently unknown. METHODS:To i...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2017.07.015
更新日期:2017-10-01 00:00:00
abstract:OBJECTIVE:A significant portion of the heritable risk for complex metabolic disorders cannot be attributed to classic Mendelian genetic factors. At least some of this missing heritability is thought to be due to the epigenetic influence of parental and grandparental metabolic state on offspring health. Previous work su...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2017.03.012
更新日期:2017-04-26 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
abstract:OBJECTIVE:Glucose-stimulated insulin secretion in pancreatic beta cells requires metabolic signals including the generation of glucose-derived short chain acyl-CoAs in the cytosol from mitochondrially-derived metabolites. One concept of insulin secretion is that ATP citrate lyase generates short chain acyl-CoAs in the ...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2016.07.011
更新日期:2016-08-08 00:00:00
abstract:OBJECTIVE:We tested the hypothesis that skeletal muscle of endurance-trained male runners would exhibit elevated autophagy and mitophagy markers, which would be associated with greater metabolic flexibility following a high-fat meal (HFM). METHODS:Muscle biopsies were collected to determine differences in autophagy an...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2017.10.006
更新日期:2017-12-01 00:00:00
abstract:OBJECTIVE:The mechanisms behind the efficacy of bariatric surgery (BS) for treating obesity and type 2 diabetes, particularly with respect to the influence of the small bowel, remain poorly understood. In vitro and animal models are suboptimal with respect to their ability to replicate the human intestinal epithelium u...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2020.101129
更新日期:2020-11-25 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:OBJECTIVES:IL-13 is a cytokine classically produced by anti-inflammatory T-helper-2 lymphocytes; it is decreased in the circulation of type 2 diabetic patients and impacts positively on liver and skeletal muscle. Although IL-13 can exert positive effects on beta-cell lines, its impact and mode of action on primary beta...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2015.11.003
更新日期:2015-11-17 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::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:OBJECTIVE:Aging and weight gain lead to a decline in brown and beige adipocyte functionality that exacerbates obesity and insulin resistance. We sought to determine whether sphingolipids, such as ceramides, a class of lipid metabolites that accumulate in aging and overnutrition, are sufficient or necessary for the meta...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2020.101145
更新日期:2020-12-19 00:00:00
abstract:OBJECTIVE:Leptin is a cytokine produced by adipose tissue that acts mainly on the hypothalamus to regulate appetite and energy homeostasis. Previous studies revealed that the leptin receptor is expressed not only in neurons, but also in glial cells. Microglia are resident immune cells in the brain that play an essentia...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2017.11.003
更新日期:2018-01-01 00:00:00
abstract:OBJECTIVE:Strategies improving skeletal muscle mitochondrial capacity are commonly paralleled by improvements in (metabolic) health. We and others previously identified microRNAs regulating mitochondrial oxidative capacity, but data in skeletal muscle are limited. Therefore, the present study aimed to identify novel mi...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2017.08.007
更新日期:2017-11-01 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:Hypothalamic agouti-related peptide (AgRP) and pro-opiomelanocortin (POMC) expressing neurons play critical roles in control of energy balance. Glutamatergic input via n-methyl-d-aspartate receptors (NMDARs) is pivotal for regulation of neuronal activity and is required in AgRP neurons for normal body weight ...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2015.06.010
更新日期:2015-07-06 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: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:During pregnancy, women normally increase their food intake and body fat mass, and exhibit insulin resistance. However, an increasing number of women are developing metabolic imbalances during pregnancy, including excessive gestational weight gain and gestational diabetes mellitus. Despite the negative health...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2014.12.005
更新日期:2014-12-19 00:00:00
abstract:BACKGROUND:In addition to their crucial role in reproduction, estrogens are key regulators of energy and glucose homeostasis and they also exert several cardiovascular protective effects. These beneficial actions are mainly mediated by estrogen receptor alpha (ERα), which is widely expressed in metabolic and vascular t...
journal_title:Molecular metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.molmet.2018.05.009
更新日期:2018-09-01 00:00:00
abstract:OBJECTIVE:Studies using the estrogen receptor alpha (ERα) knock-out (αERKO) mice have demonstrated that ERα plays a crucial role in various estrogen-mediated metabolic regulations. ERα is a ligand dependent transcription regulator and its activity is regulated by estrogenic compounds. ERα consists of two transcriptiona...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2018.09.006
更新日期:2018-12-01 00:00:00
abstract:BACKGROUND:Recent 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, ...
journal_title:Molecular metabolism
pub_type: 杂志文章,评审
doi:10.1016/j.molmet.2018.10.008
更新日期:2019-01-01 00:00:00
abstract:OBJECTIVE:Besides functioning as an intracellular metabolite, succinate acts as a stress-induced extracellular signal through activation of GPR91 (SUCNR1) for which we lack suitable pharmacological tools. METHODS AND RESULTS:Here we first determined that the cis conformation of the succinate backbone is preferred and ...
journal_title:Molecular metabolism
pub_type: 杂志文章
doi:10.1016/j.molmet.2017.09.005
更新日期:2017-12-01 00:00:00