Uncoupling protein 1 expression does not protect mice from diet-induced obesity

We studied the metabolic phenotype of a novel Ucp1-LUC-iRFP713 knock-in reporter gene mouse model originally generated to monitor endogenous Ucp1 gene expression. Both reporter mice and reporter cells reliably reflected Ucp1 gene expression in vivo and in vitro. We here report an unexpected reduction in UCP1 content in homozygous knock-in (KI) reporter mice. As a result, the thermogenic capacity of KI mice stimulated by norepinephrine was largely blunted, making them more sensitive to an acute cold exposure. In return, these reporter mice with reduced UCP1 expression enabled us to investigate the physiological role of UCP1 in the prevention of weight gain. We observed no substantial differences in body mass across the three genotypes, irrespective of the type of diet or the ambient temperature, possibly due to the insufficient UCP1 activation. Indeed, activation of UCP1 by daily injection of the selective β3-adrenergic receptor agonist CL316,243 resulted in significantly greater reduction of body weight in WT mice than in KI mice. Taken together, we conclude that the intact expression of UCP1 is essential for cold-induced thermogenesis but the presence of UCP1 per se does not protect mice from diet-induced obesity.

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Serial analysis of gene expression (SAGE) during porcine embryo development

Reproduction Fertility and Development ◽

10.1071/rd03081 ◽

2004 ◽

Vol 16 (2) ◽

pp. 87 ◽

Cited By ~ 12

Author(s):

Le Ann Blomberg ◽

Kurt A. Zuelke

Keyword(s):

Gene Expression ◽

Functional Genomics ◽

Embryo Development ◽

Molecular Mechanisms ◽

Physiological Role ◽

Transgenic Animals ◽

Specific Gene ◽

Research Strategies

Functional genomics provides a powerful means for delving into the molecular mechanisms involved in pre-implantation development of porcine embryos. High rates of embryonic mortality (30%), following either natural mating or artificial insemination, emphasise the need to improve the efficiency of reproduction in the pig. The poor success rate of live offspring from in vitro-manipulated pig embryos also hampers efforts to generate transgenic animals for biotechnology applications. Previous analysis of differential gene expression has demonstrated stage-specific gene expression for in vivo-derived embryos and altered gene expression for in vitro-derived embryos. However, the methods used to date examine relatively few genes simultaneously and, thus, provide an incomplete glimpse of the physiological role of these genes during embryogenesis. The present review will focus on two aspects of applying functional genomics research strategies for analysing the expression of genes during elongation of pig embryos between gestational day (D) 11 and D12. First, we compare and contrast current methodologies that are being used for gene discovery and expression analysis during pig embryo development. Second, we establish a paradigm for applying serial analysis of gene expression as a functional genomics tool to obtain preliminary information essential for discovering the physiological mechanisms by which distinct embryonic phenotypes are derived.

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Exposure to the Widely Used Pyrethroid Pesticide Deltamethrin, Does Not Exacerbate High Fat Diet Induced Obesity or Insulin Resistance in C57BL/6J Mice

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.090 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A45-A46

Author(s):

Evangelia Evelyn Tsakiridis ◽

Marisa Morrow ◽

Andrea Llanos ◽

Bo Wang ◽

Alison Holloway ◽

...

Keyword(s):

Insulin Resistance ◽

Glycemic Control ◽

Metabolic Diseases ◽

Uncoupling Protein ◽

Diet Induced Obesity ◽

Brown Adipose ◽

Pyrethroid Pesticide ◽

First Time

Abstract Deltamethrin is a commonly used pesticide for the control of mosquito populations. Despite widespread use, the effects of deltamethrin on adiposity and glucose homeostasis have been equivocal with some studies showing increased, decreased and no effect on adiposity and glycemic control. However, no study to date has investigated the effect of deltamethrin in mice housed at thermoneutral temperatures, which is important for modelling metabolic diseases in rodents due to reduced thermal stress and constitutive activation of brown adipose tissue. In the current study we demonstrate for the first time that deltamethrin reduces uncoupling protein-1 expression in brown adipocytes cultured in vitro at concentrations as low as 1pm. Meanwhile, in-vivo deltamethrin does not appear to alter glycemic control or promote adiposity at exposures equivalent to 0.01, 0.1 or 1.0 mg/kg/day. Together, our study demonstrates environmentally relevant exposure to deltamethrin does not exacerbate diet induced obesity or insulin resistance.

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Diet-Derived Polyphenol Metabolite Enterolactone Is a Tissue-Specific Estrogen Receptor Activator

Endocrinology ◽

10.1210/en.2007-0289 ◽

2007 ◽

Vol 148 (10) ◽

pp. 4875-4886 ◽

Cited By ~ 97

Author(s):

Pauliina Penttinen ◽

Jan Jaehrling ◽

Anastasios E. Damdimopoulos ◽

José Inzunza ◽

Josephine G. Lemmen ◽

...

Keyword(s):

Gene Expression ◽

Ligand Binding ◽

Estrogenic Activity ◽

Culture Conditions ◽

Mouse Uterus ◽

Tissue Specific ◽

Dietary Polyphenols ◽

Reporter Mice

Numerous dietary compounds can modify gene expression by binding to the members of the nuclear receptor superfamily of transcription factors. For example, dietary polyphenols, such as soy isoflavones genistein and daidzein, modulate the activity of the estrogen receptors (ERs)-α and ERβ. An additional class of dietary polyphenols that modulate cellular signaling pathways are lignans, compounds that are common constituents of Western diets. In this study, we show that a metabolite of dietary lignans, enterolactone, at physiological concentrations, activates ER-mediated transcription in vitro with preference for ERα. The effects of enterolactone are mediated by the ER ligand binding domain and are susceptible to antiestrogen treatment. Furthermore, the affinity of enterolactone toward ERα, measured by a novel ligand binding assay, is augmented in cell culture conditions. Moreover, our results demonstrate for the first time that enterolactone has estrogenic activity in vivo. In transgenic estrogen-sensitive reporter mice, enterolactone induces tissue-specific estrogen-responsive reporter gene expression as well as promotes uterine stromal edema and expression of estrogen-responsive endogenous genes (CyclinD1 and Ki67). Taken together, our data show that enterolactone is a selective ER agonist inducing ER-mediated transcription both in vitro in different cell lines and in vivo in the mouse uterus.

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β-adrenergic Receptor Stimulation Revealed a Novel Regulatory Pathway via Suppressing Histone Deacetylase 3 to Induce Uncoupling Protein 1 Expression in Mice Beige Adipocyte

International Journal of Molecular Sciences ◽

10.3390/ijms19082436 ◽

2018 ◽

Vol 19 (8) ◽

pp. 2436 ◽

Cited By ~ 5

Author(s):

Ana Yuliana ◽

Huei-Fen Jheng ◽

Satoko Kawarasaki ◽

Wataru Nomura ◽

Haruya Takahashi ◽

...

Keyword(s):

Histone Deacetylase ◽

Transcriptional Activation ◽

Adrenergic Receptor ◽

Uncoupling Protein ◽

Open Chromatin ◽

Uncoupling Protein 1 ◽

Beige Adipocyte ◽

Ucp1 Expression

Browning of adipose tissue has been prescribed as a potential way to treat obesity, marked by the upregulation of uncoupling protein 1 (Ucp1). Several reports have suggested that histone deacetylase (HDAC) might regulate Ucp1 by remodelling chromatin structure, although the mechanism remains unclear. Herein, we investigate the effect of β-adrenergic receptor (β-AR) activation on the chromatin state of beige adipocyte. β-AR-stimulated Ucp1 expression via cold (in vivo) and isoproterenol (in vitro) resulted in acetylation of histone activation mark H3K27. H3K27 acetylation was also seen within Ucp1 promoter upon isoproterenol addition, favouring open chromatin for Ucp1 transcriptional activation. This result was found to be associated with the downregulation of class I HDAC mRNA, particularly Hdac3 and Hdac8. Further investigation showed that although HDAC8 activity decreased, Ucp1 expression was not altered when HDAC8 was activated or inhibited. In contrast, HDAC3 mRNA and protein levels were simultaneously downregulated upon isoproterenol addition, resulting in reduced recruitment of HDAC3 to the Ucp1 enhancer region, causing an increased H3K27 acetylation for Ucp1 upregulation. The importance of HDAC3 inhibition was confirmed through the enhanced Ucp1 expression when the cells were treated with HDAC3 inhibitor. This study highlights the novel mechanism of HDAC3-regulated Ucp1 expression during β-AR stimulation.

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UCP3 and its putative function: consistencies and controversies

Biochemical Society Transactions ◽

10.1042/bst0290768 ◽

2001 ◽

Vol 29 (6) ◽

pp. 768-773 ◽

Cited By ~ 18

Author(s):

M.-E. Harper ◽

R. M. Dent ◽

V. Bezaire ◽

A. Antoniou ◽

A. Gauthier ◽

...

Keyword(s):

Fatty Acid ◽

Uncoupling Protein ◽

Expression Patterns ◽

Physiological Role ◽

In Vivo Studies ◽

Proton Leak ◽

Acid Oxidation ◽

Mitochondrial Uncoupling

The physiological function of uncoupling protein 3 (UCP3) is as yet unknown. Based on its 57% homology to UCP1 whose physiologic function is uncoupling and thermogenesis, UCP3 was attributed with the function of mitochondrial uncoupling through proton-leak reactions. UCP3 is expressed selectively in muscle, a tissue in which it has been estimated that proton leak accounts for approx. 50% of resting energy metabolism. Genetic linkage, association and variant studies suggest a role for UCP3 in obesity and/or diabetes. Studies of the heterologous expression of UCP3 in yeast provide support for the idea that UCP3 can uncouple mitochondrial oxidative phosphorylation, but the physiological relevance of these results is questionable. In vitro studies of mitochondria from Ucp3− − mice provide support, but there are no changes in resting metabolic rate (RMR) of mice. In vivo studies demonstrate increased ATP synthesis, but estimates of substrate oxidation rate indicate no change. Mice that greatly overexpress Ucp3 in muscle have increased RMR. Inconsistent with the function of uncoupling are the observations that fasting results in increased expression of UCP3, but no change in muscle proton leak. Moreover, fasting decreases energy expenditure in muscle. Expression patterns for Ucp3 and lipid-metabolism genes support a physiological role in fatty acid oxidation. Overall, findings support a role for Ucp3 in fatty acid metabolism that may have implications for obesity and/or Type II diabetes.

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Progress in micro RNA focused research in endocrinology

Endocrine Regulations ◽

10.1515/enr-2016-0012 ◽

2016 ◽

Vol 50 (2) ◽

pp. 83-105 ◽

Cited By ~ 1

Author(s):

K. Voglova ◽

J. Bezakova ◽

Iveta Herichova

Keyword(s):

Gene Expression ◽

Physiological Role ◽

Micro Rna ◽

Mirna Biogenesis ◽

Rna Molecules ◽

Micro Rnas ◽

Influence Gene Expression

AbstractMicro RNAs (miRNAs) are small regulatory molecules of increasing biologists’ interest. miRNAs, unlikely mRNA, do not encode proteins. It is a class of small double stranded RNA molecules that via their seed sequence interact with mRNA and inhibit its expression. It has been estimated that 30% of human gene expression is regulated by miRNAs. One miRNA usually targets several mRNAs and one mRNA can be regulated by several miRNAs. miRNA biogenesis is realized by key enzymes, Drosha and Dicer. miRNA/mRNA interaction depends on binding to RNA-induced silencing complex. Today, complete commercially available methodical proposals for miRNA investigation are available. There are techniques allowing the identification of new miRNAs and new miRNA targets, validation of predicted targets, measurement of miRNAs and their precursor levels, and validation of physiological role of miRNAs under in vitro and in vivo conditions. miRNAs have been shown to influence gene expression in several endocrine glands, including pancreas, ovary, testes, hypothalamus, and pituitary.

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Identification of genes early responsive to gamma-irradiation in isolated rat hepatocytes in vitro and rat liver in vivo by cDNA array gene expression analysis

Zeitschrift für Gastroenterologie ◽

10.1055/s-2005-920060 ◽

2005 ◽

Vol 43 (05) ◽

Author(s):

DS Batusic ◽

H Christiansen ◽

B Saile ◽

RM Hermann ◽

J Dudas ◽

...

Keyword(s):

Gene Expression ◽

Gamma Irradiation ◽

Rat Liver ◽

Gene Expression Analysis ◽

Cdna Array ◽

Rat Hepatocytes ◽

Isolated Rat Hepatocytes ◽

Isolated Rat

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Effect of X-irradiation on gene expression of rat liver chemokines: in vivo and in vitro studies

Zeitschrift für Gastroenterologie ◽

10.1055/s-2008-1037499 ◽

2008 ◽

Vol 46 (01) ◽

Cited By ~ 1

Author(s):

F Moriconi ◽

H Christiansen ◽

N Sheikh ◽

J Dudas ◽

...

Keyword(s):

Gene Expression ◽

Rat Liver ◽

In Vitro Studies ◽

X Irradiation

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Vibrio harveyi virulence gene expression in vitro and in vivo during infection in black tiger shrimp Penaeus monodon

Diseases of Aquatic Organisms ◽

10.3354/dao03475 ◽

2020 ◽

Vol 139 ◽

pp. 153-160

Author(s):

S Peeralil ◽

TC Joseph ◽

V Murugadas ◽

PG Akhilnath ◽

VN Sreejith ◽

...

Keyword(s):

Gene Expression ◽

Virulence Genes ◽

Vibrio Harveyi ◽

Penaeus Monodon ◽

Challenge Test ◽

Virulence Gene ◽

Economic Losses ◽

Virulence Gene Expression

Luminescent Vibrio harveyi is common in sea and estuarine waters. It produces several virulence factors and negatively affects larval penaeid shrimp in hatcheries, resulting in severe economic losses to shrimp aquaculture. Although V. harveyi is an important pathogen of shrimp, its pathogenicity mechanisms have yet to be completely elucidated. In the present study, isolates of V. harveyi were isolated and characterized from diseased Penaeus monodon postlarvae from hatcheries in Kerala, India, from September to December 2016. All 23 tested isolates were positive for lipase, phospholipase, caseinase, gelatinase and chitinase activity, and 3 of the isolates (MFB32, MFB71 and MFB68) showed potential for significant biofilm formation. Based on the presence of virulence genes, the isolates of V. harveyi were grouped into 6 genotypes, predominated by vhpA+ flaB+ ser+ vhh1- luxR+ vopD- vcrD+ vscN-. One isolate from each genotype was randomly selected for in vivo virulence experiments, and the LD50 ranged from 1.7 ± 0.5 × 103 to 4.1 ± 0.1 × 105 CFU ml-1. The expression of genes during the infection in postlarvae was high in 2 of the isolates (MFB12 and MFB32), consistent with the result of the challenge test. However, in MFB19, even though all genes tested were present, their expression level was very low and likely contributed to its lack of virulence. Because of the significant variation in gene expression, the presence of virulence genes alone cannot be used as a marker for pathogenicity of V. harveyi.

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