Intact glucose uptake despite deteriorating signaling in adipocytes with high-fat feeding.

Abstract:

:To capture immediate cellular changes during diet-induced expansion of adipocyte cell volume and number, we characterized mature adipocytes during a short-term high-fat diet (HFD) intervention. Male C57BL6/J mice were fed chow diet, and then switched to HFD for 2, 4, 6 or 14 days. Systemic glucose clearance was assessed by glucose tolerance test. Adipose tissue was dissected for RNA-seq and cell size distribution analysis using coulter counting. Insulin response in isolated adipocytes was monitored by glucose uptake assay and Western blotting, and confocal microscopy was used to assess autophagic activity. Switching to HFD was accompanied by an immediate adipocyte size expansion and onset of systemic insulin resistance already after two days, followed by recruitment of new adipocytes. Despite an initially increased non-stimulated and preserved insulin-stimulated glucose uptake, we observed a decreased phosphorylation of insulin receptor substrate-1 (IRS-1) and protein kinase B (PKB). After 14 days of HFD, both the insulin-stimulated phosphorylation of Akt substrate of 160 kDa (AS160) and glucose uptake was blunted. RNA-seq analysis of adipose tissue revealed transient changes in gene expression at day four, including highly significant upregulation of Trp53inp, previously demonstrated to be involved in autophagy. We confirmed increased autophagy, measured as an increased density of LC3-positive puncta and decreased p62 expression after 14 days of HFD. In conclusion, HFD rapidly induced systemic insulin resistance, whereas insulin-stimulated glucose uptake remained intact throughout 6 days of HFD feeding. We also identified autophagy as an early cellular process that potentially influences adipocyte function upon switching to HFD.

journal_name

J Mol Endocrinol

authors

Hansson B,Wasserstrom S,Morén B,Periwal V,Vikman P,Cushman SW,Göransson O,Storm P,Stenkula KG

doi

10.1530/JME-17-0195

subject

Has Abstract

pub_date

2018-04-01 00:00:00

pages

199-211

issue

3

eissn

0952-5041

issn

1479-6813

pii

JME-17-0195

journal_volume

60

pub_type

杂志文章
  • Modulation of monocarboxylate transporter 8 oligomerization by specific pathogenic mutations.

    abstract::The monocarboxylate transporter 8 (MCT8) is a member of the major facilitator superfamily (MFS). These membrane-spanning proteins facilitate translocation of a variety of substrates, MCT8 specifically transports iodothyronines. Mutations in MCT8 are the underlying cause of severe X-linked psychomotor retardation. At t...

    journal_title:Journal of molecular endocrinology

    pub_type: 杂志文章

    doi:10.1530/JME-14-0272

    authors: Fischer J,Kleinau G,Müller A,Kühnen P,Zwanziger D,Kinne A,Rehders M,Moeller LC,Führer D,Grüters A,Krude H,Brix K,Biebermann H

    更新日期:2015-02-01 00:00:00

  • Selective activation of the probasin androgen-responsive region by steroid hormones.

    abstract::Glucocorticoid and androgen receptors have been shown to function through the same palindromic glucocorticoid response element (GRE) and yet have differential effects on gene transcription. In this study, we examined the functional and structural relationship of the androgen and glucocorticoid receptors with the andro...

    journal_title:Journal of molecular endocrinology

    pub_type: 杂志文章

    doi:10.1677/jme.0.0220313

    authors: Kasper S,Rennie PS,Bruchovsky N,Lin L,Cheng H,Snoek R,Dahlman-Wright K,Gustafsson JA,Shiu RP,Sheppard PC,Matusik RJ

    更新日期:1999-06-01 00:00:00

  • Influence of oestradiol and tamoxifen on oestrogen receptors-alpha and -beta protein degradation and non-genomic signalling pathways in uterine and breast carcinoma cells.

    abstract::Tamoxifen acts as an oestrogen antagonist in the breast reducing cell proliferation, but in the uterus as an oestrogen agonist resulting in increased cell proliferation. Tamoxifen exerts its tissue-specific effects through the oestrogen receptors (ERalpha or ERbeta). The levels and functions of the two ERs affect the ...

    journal_title:Journal of molecular endocrinology

    pub_type: 杂志文章

    doi:10.1677/jme.1.01784

    authors: Horner-Glister E,Maleki-Dizaji M,Guerin CJ,Johnson SM,Styles J,White IN

    更新日期:2005-12-01 00:00:00

  • Multiple alternative splice isoforms of parathyroid hormone-related peptide mRNA in human cell lines.

    abstract::Parathyroid hormone-related peptide (PTHrP) is thought to be responsible for hypercalcemia in some patients with malignant tumors. The PTHrP gene has seven exons, giving rise to three types of PTHrP isoform through alternative splicing. We studied the expression of mRNAs in 14 human cell lines using the reverse transc...

    journal_title:Journal of molecular endocrinology

    pub_type: 杂志文章

    doi:10.1677/jme.0.0150245

    authors: Nakamura M,Hashimoto T,Furuyama J,Kakudo K

    更新日期:1995-12-01 00:00:00

  • Activation of GLP-1 receptor enhances the chemosensitivity of pancreatic cancer cells.

    abstract::This study aimed to determine whether and how the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide affects the chemoresistance and chemosensitivity of pancreatic cancer cells to gemcitabine in vitro and in vivo. The GLP-1R and protein kinase A (PKA) levels were compared between the human pancreatic cancer...

    journal_title:Journal of molecular endocrinology

    pub_type: 杂志文章

    doi:10.1530/JME-19-0186

    authors: Zhao HJ,Jiang X,Hu LJ,Yang L,Deng LD,Wang YP,Ren ZP

    更新日期:2020-02-01 00:00:00

  • The combinations of polymorphisms in vitamin D receptor, osteoprotegerin and tumour necrosis factor superfamily member 11 genes are associated with bone mineral density.

    abstract::1alpha,25-dihydroxyvitamin D(3) upregulates tumour necrosis factor superfamily member 11 (TNFSF11) that codes for the receptor activator of nuclear factor kappaB ligand (RANKL), and downregulates osteoprotegerin (OPG) expression. We have analyzed the individual effects of polymorphisms in the vitamin D receptor gene (...

    journal_title:Journal of molecular endocrinology

    pub_type: 杂志文章

    doi:10.1677/JME-08-0108

    authors: Mencej-Bedrac S,Prezelj J,Kocjan T,Teskac K,Ostanek B,Smelcer M,Marc J

    更新日期:2009-03-01 00:00:00

  • IGF system in sarcomas: a crucial pathway with many unknowns to exploit for therapy.

    abstract::The insulin-like growth factor (IGF) system has gained substantial interest due to its involvement in regulating cell proliferation, differentiation and survival during anoikis and after conventional and targeted therapies. However, results from clinical trials have been largely disappointing, with only a few but nota...

    journal_title:Journal of molecular endocrinology

    pub_type: 杂志文章,评审

    doi:10.1530/JME-17-0250

    authors: Mancarella C,Scotlandi K

    更新日期:2018-07-01 00:00:00

  • Molecular cloning and characterization of alpha1-soluble guanylyl cyclase gene promoter in rat pituitary cells.

    abstract::Soluble guanylyl cyclase is a cytosolic enzyme which catalyzes conversion of GTP to the second messenger cyclic GMP. The transcriptional regulation at the promoter levels of four soluble guanylyl cyclase subunits, termed alpha1, alpha2, beta1, and beta2, is largely unknown. In this study, we identified the transcripti...

    journal_title:Journal of molecular endocrinology

    pub_type: 杂志文章

    doi:10.1677/jme.1.02180

    authors: Jiang Y,Stojilkovic SS

    更新日期:2006-12-01 00:00:00

  • Transcriptional activation of cathepsin D gene expression by growth factors.

    abstract::Insulin-like growth factor-I (IGF-I), transforming growth factor alpha (TGFalpha) and epidermal growth factor (EGF) induced cathepsin D gene expression and reporter gene activity in MCF-7 human breast cancer cells transiently transfected with a construct (pCD1) containing a -2576 to -124 cathepsin D gene promoter inse...

    journal_title:Journal of molecular endocrinology

    pub_type: 杂志文章

    doi:10.1677/jme.0.0240193

    authors: Wang F,Duan R,Chirgwin J,Safe SH

    更新日期:2000-04-01 00:00:00

  • The two most common alleles of the coding GGN repeat in the androgen receptor gene cause differences in protein function.

    abstract::Genetic studies have reported association of a polyglycine-encoding GGN repeat in exon 1 of the androgen receptor (AR) gene with common human traits. The polyglycine tract is located in the transactivating domain of the AR protein, suggesting an effect of repeat length on receptor function. Here, we compare the functi...

    journal_title:Journal of molecular endocrinology

    pub_type: 杂志文章

    doi:10.1677/JME-06-0072

    authors: Brockschmidt FF,Nöthen MM,Hillmer AM

    更新日期:2007-07-01 00:00:00

  • Creation of a fully active, cytosolic form of human type I 3beta-hydroxysteroid dehydrogenase/isomerase by the deletion of a membrane-spanning domain.

    abstract::Human 3beta-hydroxysteroid dehydrogenase/steroid Delta(5)-Delta(4)-isomerase (3beta-HSD/isomerase) is a bifunctional, single enzyme protein that is membrane-bound in the endoplasmic reticulum (microsomes) and mitochondria of cells in the placenta (type I) and in the adrenals and gonads (type II). Two membrane-binding ...

    journal_title:Journal of molecular endocrinology

    pub_type: 杂志文章

    doi:10.1677/jme.0.0230231

    authors: Thomas JL,Evans BW,Blanco G,Mason JI,Strickler RC

    更新日期:1999-10-01 00:00:00

  • Effects of essential amino acids on lipid metabolism in mice and humans.

    abstract::Eight amino acids are considered essential for human nutrition, and three of them, including leucine, isoleucine and valine, are called as branched-chain amino acids (BCAAs). We recently discovered that dietary deficiency of any BCAA for 7 days rapidly reduces the abdominal fat mass in mice. The goal of this study was...

    journal_title:Journal of molecular endocrinology

    pub_type: 杂志文章

    doi:10.1530/JME-16-0116

    authors: Xiao F,Du Y,Lv Z,Chen S,Zhu J,Sheng H,Guo F

    更新日期:2016-11-01 00:00:00

  • Characterization of human relaxin gene regulation in the relaxin-expressing human prostate adenocarcinoma cell line LNCaP.FGC.

    abstract::Relaxin is a peptide hormone which is produced in human reproductive tissues including the ovary and prostate gland. Little is known of the molecular events regulating relaxin gene transcription. We have studied this question using gene transfer of relaxin promoter/reporter gene constructs into a relaxin-expressing ce...

    journal_title:Journal of molecular endocrinology

    pub_type: 杂志文章

    doi:10.1677/jme.0.0150153

    authors: Gunnersen JM,Roche PJ,Tregear GW,Crawford RJ

    更新日期:1995-10-01 00:00:00

  • Multiple forms of angiotensin II receptors in rat tissues.

    abstract::Angiotensin II (AII) receptors were identified in rat tissue membranes by specific binding of 125I-labelled AII. Using an isoelectric focusing technique, two forms of the high-affinity AII receptor were identified in rat adrenal zona glomerulosa and liver membranes. These migrated to isoelectric points (pI) 6.8 and 6....

    journal_title:Journal of molecular endocrinology

    pub_type: 杂志文章

    doi:10.1677/jme.0.0070021

    authors: Jimenez E,Marsigliante S,Barker S,Hinson JP,Vinson GP

    更新日期:1991-08-01 00:00:00

  • Beta2-adrenoceptor desensitization in non-pregnant estrogen-primed rat myometrium involves modulation of oxytocin receptor gene expression.

    abstract::The nona-peptide oxytocin (OT) induces contraction of the myometrium by interaction with specific plasma membrane associated OT receptors (OTR), whereas stimulation of beta2-adrenoceptors (beta2AR) causes relaxation. Homologous desensitization of the myometrium to both hormones has been described. However, a possible ...

    journal_title:Journal of molecular endocrinology

    pub_type: 杂志文章

    doi:10.1677/jme.0.0200261

    authors: Engstrøm T,Bratholm P,Vilhardt H,Christensen NJ

    更新日期:1998-04-01 00:00:00

  • IGF-independent effects of IGFBP-2 on the human breast cancer cell line Hs578T.

    abstract::There is evidence that insulin-like growth factor-binding protein (IGFBP-2), a modulator of the actions of IGFs, also has IGF-independent effects in human tumor cell lines. These involve specific binding of IGFBP-2 to alpha5beta1-integrin, followed by alterations in the phosphorylation status of downstream signaling m...

    journal_title:Journal of molecular endocrinology

    pub_type: 杂志文章

    doi:10.1677/jme.1.01955

    authors: Frommer KW,Reichenmiller K,Schutt BS,Hoeflich A,Ranke MB,Dodt G,Elmlinger MW

    更新日期:2006-08-01 00:00:00

  • Insulin-like growth factor (IGF)-I A- and B-domain analogues with altered type 1 IGF and insulin receptor binding specificities.

    abstract::Insulin-like growth factor-I (IGF-I) analogues were produced with the aim of identifying IGF-I residues that contribute to the specificity of binding to the type 1 IGF receptor as opposed to the insulin receptor. Receptor binding properties of a series of A- and B-domain analogues were compared using rat L6 myoblasts,...

    journal_title:Journal of molecular endocrinology

    pub_type: 杂志文章

    doi:10.1677/jme.0.0170237

    authors: Shooter GK,Magee B,Soos MA,Francis GL,Siddle K,Wallace JC

    更新日期:1996-12-01 00:00:00

  • Functional expression of the oxytocin receptor in Xenopus laevis oocytes primed with mRNA from bovine endometrium.

    abstract::Synthesis of the uterine receptor for the hypothalamic hormone oxytocin has been induced in oocytes from Xenopus laevis previously primed with bovine endometrium mRNA. The injected oocytes responded to oxytocin by showing dose-dependent oscillations in membrane currents as recorded by the voltage-clamp method. The res...

    journal_title:Journal of molecular endocrinology

    pub_type: 杂志文章

    doi:10.1677/jme.0.0010077

    authors: Morley SD,Meyerhof W,Schwarz J,Richter D

    更新日期:1988-07-01 00:00:00

  • Adiponectin limits differentiation and trophoblast invasion in human endometrial cells.

    abstract::Successful human embryo implantation requires a proper differentiation of endometrial stromal cells (ESCs) into decidual cells, during a process called decidualization. ESCs express specific molecules, such as prolactin, insulin-like growth factor-binding protein-1 (IGFBP-1) and connexin-43. Decidual cells are also in...

    journal_title:Journal of molecular endocrinology

    pub_type: 杂志文章

    doi:10.1530/JME-17-0046

    authors: Duval F,Dos Santos E,Moindjie H,Serazin V,Swierkowski-Blanchard N,Vialard F,Dieudonné MN

    更新日期:2017-10-01 00:00:00

  • Directed expression of simian virus 40 T-antigen in transgenic mice using the epidermal growth factor gene promoter.

    abstract::A transgenic mouse line (EGF/Tag) has been established in which expression of SV40 T-antigen is directed by a 5.5 kb fragment of the 5'-flanking region of the mouse epidermal growth factor (EGF) gene. Of the two principal sites of EGF expression in mice, submaxillary gland and kidney, T-antigen mRNA and protein were d...

    journal_title:Journal of molecular endocrinology

    pub_type: 杂志文章

    doi:10.1677/jme.0.0120313

    authors: Pascall IC,Surani MA,Barton SC,Vaughan TJ,Brown KD

    更新日期:1994-06-01 00:00:00

  • 3,5-T2 alters murine genes relevant for xenobiotic, steroid, and thyroid hormone metabolism.

    abstract::The endogenous thyroid hormone (TH) metabolite 3,5-diiodo-l-thyronine (3,5-T2) acts as a metabolically active substance affecting whole-body energy metabolism and hepatic lipid handling in a desirable manner. Considering possible adverse effects regarding thyromimetic action of 3,5-T2 treatment in rodents, the current...

    journal_title:Journal of molecular endocrinology

    pub_type: 杂志文章

    doi:10.1530/JME-15-0159

    authors: Lietzow J,Golchert J,Homuth G,Völker U,Jonas W,Köhrle J

    更新日期:2016-05-01 00:00:00

  • Heme oxygenase-1 arrests Leydig cells functions and impairs their regulation by histamine.

    abstract::Testicular Leydig cells (LC) are modulated by several pathways, one of them being the histaminergic system. Heme oxygenase-1 (HO-1), whose upregulation comprises the primary response to oxidative noxae, has a central homeostatic role and might dysregulate LC functions when induced. In this report, we aimed to determin...

    journal_title:Journal of molecular endocrinology

    pub_type: 杂志文章

    doi:10.1530/JME-19-0063

    authors: Raices T,Varela ML,Monzón CM,Correa Torrado MF,Pagotto RM,Besio Moreno M,Mondillo C,Pignataro OP,Pereyra EN

    更新日期:2019-10-01 00:00:00

  • Effects of antioestrogens on the proliferation of MCF-7 human breast cancer cells.

    abstract::Non-steroidal antioestrogens, such as tamoxifen, inhibit the growth of human breast cancer cells. The experiments described here compare and contrast the efficacy of tamoxifen and the 'pure' antioestrogen, ICI 164384, on the inhibition of proliferation of MCF-7 cells. Previous studies have shown that ICI 164384 has a ...

    journal_title:Journal of molecular endocrinology

    pub_type: 杂志文章

    doi:10.1677/jme.0.0020225

    authors: Wakeling AE,Newboult E,Peters SW

    更新日期:1989-05-01 00:00:00

  • Evidence that the mouse insulin receptor substrate-1 belongs to the gene family on which the promoter is activated by estrogen receptor alpha through its interaction with Sp1.

    abstract::In the present study, the molecular mechanism underlying the up-regulatory effect of estradiol (E2) on mouse insulin receptor substrate-1 (IRS-1) promoter was investigated in CHO cells on which the same promoter had first been functionally characterized. The mouse IRS-1 promoter bears four consensus half Estrogen Resp...

    journal_title:Journal of molecular endocrinology

    pub_type: 杂志文章

    doi:10.1677/jme.1.01848

    authors: Panno ML,Mauro L,Marsico S,Bellizzi D,Rizza P,Morelli C,Salerno M,Giordano F,Andò S

    更新日期:2006-02-01 00:00:00

  • Transcriptional regulation of the rat apelin receptor gene: promoter cloning and identification of an Sp1 site necessary for promoter activity.

    abstract::The genomic structure and transcriptional regulation of the rat apelin receptor (APJR) were analysed by rapid amplification of 5' cDNA ends (5'-RACE), transient expression assays and DNA-protein interaction. Analysis of the 5'-flanking region of a rat genomic clone shows no TATA box, but a putative CAAT box and severa...

    journal_title:Journal of molecular endocrinology

    pub_type: 杂志文章

    doi:10.1677/jme.1.01927

    authors: O'Carroll AM,Lolait SJ,Howell GM

    更新日期:2006-02-01 00:00:00

  • Immunoelectron microscopic localization of 3beta-hydroxysteroid dehydrogenase and type 5 17beta-hydroxysteroid dehydrogenase in the human prostate and mammary gland.

    abstract::The subcellular distribution of steroidogenic enzymes has so far been studied mostly in classical endocrine glands and in the placenta. In the peripheral intracrine organs which synthesize sex steroids there is no indication about the organelles which contain the enzymes involved in steroid biosynthesis. We have thus ...

    journal_title:Journal of molecular endocrinology

    pub_type: 历史文章,杂志文章

    doi:10.1677/jme.0.0260011

    authors: Pelletier G,Luu-The V,El-Alfy M,Li S,Labrie F

    更新日期:2001-02-01 00:00:00

  • Pathway analysis of transcriptomic data shows immunometabolic effects of vitamin D.

    abstract::Unbiased genomic screening analyses have highlighted novel immunomodulatory properties of the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D). However, clearer interpretation of the resulting gene expression data is limited by cell model specificity. The aim of the current study was to provide a broader...

    journal_title:Journal of molecular endocrinology

    pub_type: 杂志文章

    doi:10.1530/JME-17-0186

    authors: Muñoz Garcia A,Kutmon M,Eijssen L,Hewison M,Evelo CT,Coort SL

    更新日期:2018-02-01 00:00:00

  • Insulin-regulated aminopeptidase in adipocyte is Cys-specific and affected by obesity.

    abstract::Insulin-regulated aminopeptidase (IRAP, EC 3.4.11.3) in adipocytes is well known to traffic between high (HDM) and low (LDM) density microsomal fractions toward the plasma membrane (MF) under stimulation by insulin. However, its catalytic preference for aminoacyl substrates with N-terminal Leu or Cys is controversial....

    journal_title:Journal of molecular endocrinology

    pub_type: 杂志文章

    doi:10.1530/JME-14-0321

    authors: Alponti RF,Viana LG,Yamanouye N,Silveira PF

    更新日期:2015-08-01 00:00:00

  • Tissue renin-angiotensin system: its expression, localization, regulation and potential role in the pancreas.

    abstract::The classical concept of the renin-angiotensin system (RAS) is that of a blood-borne cascade, whose final and bioactive product, angiotensin II, plays an important endocrine role in the maintenance of blood pressure and electrolyte as well as fluid balance. In addition to this circulating RAS, there are an increasing ...

    journal_title:Journal of molecular endocrinology

    pub_type: 杂志文章,评审

    doi:10.1677/jme.0.0260155

    authors: Leung PS,Carlsson PO

    更新日期:2001-06-01 00:00:00

  • Different effects of corticotropin-releasing factor and urocortin 2 on apoptosis of prostate cancer cells in vitro.

    abstract::Urocortin (Ucn), a corticotropin-releasing factor (CRF)-related neuropeptide binding both CRF type 1 receptor (CRFR1) and CRFR2, has recently been found in prostate cancer. However, no report has yet been known to elucidate the roles of Ucn in prostate cancer via the two receptors. In this study, the expression of bot...

    journal_title:Journal of molecular endocrinology

    pub_type: 杂志文章

    doi:10.1530/JME-11-0048

    authors: Jin L,Zhang Q,Guo R,Wang L,Wang J,Wan R,Zhang R,Xu Y,Li S

    更新日期:2011-09-07 00:00:00