The Arrestin Domain-Containing 3 Protein Regulates Body Mass and Energy Expenditure

Patwari, Parth; Emilsson, Valur; Schadt, Eric E.; Chutkow, William A.; Lee, Samuel; Marsili, Alessandro; Zhang, Yongzhao; Dobrin, Radu; Cohen, David E.; Larsen, P. Reed; Zavacki, Ann Marie; Fong, Loren G.; Young, Stephen G.; Lee, Richard T.

doi:10.1016/j.cmet.2011.08.011

Cited by 102 publications

(117 citation statements)

References 51 publications

(63 reference statements)

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“…Others have reported that Arrdc3 is required for lipid droplet formation, a gene we observed with a positive 2.4-fold change. This upregulation may drive the changes in liver lipids observed here and in other reports (26,29).…”

Section: Discussionmentioning

confidence: 48%

Genetic dissection in a mouse model reveals interactions between carotenoids and lipid metabolism

Palczewski

Widjaja‐Adhi

Amengual

et al. 2016

Journal of Lipid Research

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Section: Discussionmentioning

confidence: 48%

Genetic dissection in a mouse model reveals interactions between carotenoids and lipid metabolism

Palczewski

Widjaja‐Adhi

Amengual

et al. 2016

Journal of Lipid Research

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“…Of the candidates identified in the DIO/DR screen, several have previously been implicated in obesity development in both human subjects and in mouse models. Specifically, the arrestin domain containing three gene (Arrdc3) (up-regulated 1.6-fold in the present DIO mice) has been shown through genome-wide association scans (GWAS) to be positively associated with increased BMI in human obesity and to play a primary role in adipose tissue in regulating energy expenditure (Patwari et al 2011). Mice deficient in this gene have an obesity resistance phenotype via its positive effects on physical activity and thermogenesis (Patwari et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Contribution of the hypothalamus and gut to weight gain susceptibility and resistance in mice

Fam¹,

Sgambellone²,

Ruan³

et al. 2015

Journal of Endocrinology

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Obesity susceptibility in humans and in rodent strains varies in response to the consumption of high-energy density (HED) diets. However, the exact mechanism(s) involved in this susceptibility remain(s) unresolved. The aim of the present study was to gain greater insight into this susceptibility by using C57BL/6J (B6) mice that were separated into obesity-prone (diet-induced obese (DIO)) and obesity-resistant (diet-induced resistant (DR)) groups following an HED diet for 6 weeks. Physiological, biochemical and gene expression assessments of energy balance were performed in the DIO and DR mice on an HED diet and chow-fed mice. The increased weight gain of the DIO mice as compared to the DR mice was associated with increased energy intake and higher plasma leptin and adiponectin levels but not with reduced physical activity or resting energy expenditure. Hypothalamic Pomc gene expression was elevated, but there were no changes in Npy or Agrp expression. Adipose tissue leptin and adiponectin gene expression were significantly reduced in the DIO group as compared to the DR group. Interestingly, ileum expression of G protein-coupled receptor (Gpr) 40 (Gpr40) was significantly increased, whereas Gpr120, Gpr119, Gpr41, and glucagon-like peptide 1 (Glp1) were reduced. Contrastingly, the lower weight gain of the DR group was associated with elevated adipose tissue leptin and adiponectin gene expression, but there were no differences in plasma hormone or hypothalamic gene expression levels as compared to chow-fed mice. Therefore, the present data demonstrate that susceptibility and resistance to diet-induced weight gain in B6 mice appears to be predominantly driven by peripheral rather than hypothalamic modifications, and changes in gut-specific receptors are a potentially important contributor to this variation. Key Words" diet-induced obesity " high-energy density diet " body weight regulation

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“…For instance, Bul1/2 has a critical role in ubiquitinating and sorting the Gap1 transporter to the vacuole, whereas Art1 plays a critical role in trafficking the Mup1 transporter (Helliwell et al 2001;Soetens et al 2001;Lin et al 2008). In mammalian cells, ARRDC3 controls ubiquitination and down-regulation of b2 and b3 adrenergic receptors as well as the b4 integrin (Draheim et al 2010;Nabhan et al 2010;Patwari et al 2011;Shea et al 2012). Recent studies have shown that some a-arrestin proteins are regulated by phosphorylation, in particular kinases downstream from Tor1, thus allowing cell global regulation of plasma membrane protein levels in response to nutrient status (MacGurn et al 2011;Merhi and Andre 2012).…”

Section: Ubiquitin-dependent Sorting In Endocytosismentioning

confidence: 99%

Ubiquitin-Dependent Sorting in Endocytosis

Piper

Đikić

Lukacs

2014

Cold Spring Harbor Perspectives in Biology

181

170

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When ubiquitin (Ub) is attached to membrane proteins on the plasma membrane, it directs them through a series of sorting steps that culminate in their delivery to the lumen of the lysosome where they undergo complete proteolysis. Ubiquitin is recognized by a series of complexes that operate at a number of vesicle transport steps. Ubiquitin serves as a sorting signal for internalization at the plasma membrane and is the major signal for incorporation into intraluminal vesicles of multivesicular late endosomes. The sorting machineries that catalyze these steps can bind Ub via a variety of Ub-binding domains. At the same time, many of these complexes are themselves ubiquitinated, thus providing a plethora of potential mechanisms to regulate their activity. Here we provide an overview of how membrane proteins are selected for ubiquitination and deubiquitination within the endocytic pathway and how that ubiquitin signal is interpreted by endocytic sorting machineries. HOW PROTEINS ARE SELECTED FOR UBIQUITINATIONU biquitin (Ub) is covalently attached to substrate proteins by the concerted action of E2-conjugating enzymes and E3 ligases (Varshavsky 2012). Most of the specificity and regulation of ubiquitination is at the level of the E3 ligases, which vastly outnumber the E2-conjugating enzymes. Ubiquitination results from the transfer of Ub, held either by the E2 or in some cases by the E3 as a high-energy thioester bond, onto a substrate protein, typically on the terminal amide of a substrate acceptor lysine side chain. Owing to the intense interest in the ubiquitination system, many of the simple rules and distinctions concerning different types of ligases, their specificity for forming particular polyUb chains, and even the kinds of residues in substrate proteins that can be ubiquitin modified, have been blurred with the discovery of mixed poly-Ub chains, new enzymatic mechanisms for Ub transfer, and ubiquitination of nonlysine residues (Kulathu and Komander 2012;Wenzel and Klevit 2012;McDowell and Philpott 2013). Nonetheless, in basic terms, Ub ligases function as platforms that coordinate substrate recognition with Ub transfer as well as configuring poly-Ub chain topology by the E2-conjugating enzyme. Substrates can be bound directly by the E3 ligase or by adaptor proteins that in turn bind to ligases, and selecEditors:

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The Arrestin Domain-Containing 3 Protein Regulates Body Mass and Energy Expenditure

Cited by 102 publications

References 51 publications

Genetic dissection in a mouse model reveals interactions between carotenoids and lipid metabolism

Genetic dissection in a mouse model reveals interactions between carotenoids and lipid metabolism

Contribution of the hypothalamus and gut to weight gain susceptibility and resistance in mice

Ubiquitin-Dependent Sorting in Endocytosis

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