Nedd4 haploinsufficient mice display moderate insulin resistance, enhanced lipolysis, and protection against high-fat diet-induced obesity

Jing Jing Li, Robert J.Ferry Jr, Shiyong Diao, Bingzhong Xue, Suleiman Bahouth, Francesca-Fang Liao

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Neural precursor cell expressed developmentally down-regulated protein 4 (Nedd4) is the prototypical protein in the Nedd4 ubiquitin ligase (E3) family, which governs ubiquitin-dependent endocytosis and/or degradation of plasma membrane proteins. Loss of Nedd4 results in embryonic or neonatal lethality in mice and reduced insulin/IGF-1 signaling in embryonic fibroblasts. To delineate the roles of Nedd4 in vivo, we examined the phenotypes of heterozygous knockout mice using a high-fat diet-induced obesity (HFDIO) model. We observed that Nedd4+/- mice are moderately insulin resistant but paradoxically protected against HFDIO. After high-fat diet feeding, Nedd4+/-mice showed less body weight gain, less fat mass, and smaller adipocytes vs the wild type. Despite ameliorated HFDIO, Nedd4+/- mice did not manifest improvement in glucose tolerance vs the wild type in both genders. Nedd4+/- male, but not female, mice displayed significantly lower fasting blood glucose levels and serum insulin levels. Under obesogenic conditions, Nedd4+/- mice displayed elevated stimulated lipolytic activity, primarily through a β2-adrenergic receptor. Combined, these data support novel complex roles for Nedd4 in metabolic regulation involving altered insulin and β-adrenergic signaling pathways.

Original languageEnglish (US)
Pages (from-to)1283-1291
Number of pages9
JournalEndocrinology
Volume156
Issue number4
DOIs
StatePublished - Apr 1 2015

Fingerprint

Lipolysis
High Fat Diet
Insulin Resistance
Obesity
Insulin
Ubiquitin-Protein Ligases
Ubiquitin
Endocytosis
Insulin-Like Growth Factor I
Adipocytes
Knockout Mice
Adrenergic Agents
Adrenergic Receptors
Weight Gain
Blood Glucose
Blood Proteins
Fasting
Membrane Proteins
Proteins
Fibroblasts

All Science Journal Classification (ASJC) codes

  • Endocrinology

Cite this

Nedd4 haploinsufficient mice display moderate insulin resistance, enhanced lipolysis, and protection against high-fat diet-induced obesity. / Li, Jing Jing; Jr, Robert J.Ferry; Diao, Shiyong; Xue, Bingzhong; Bahouth, Suleiman; Liao, Francesca-Fang.

In: Endocrinology, Vol. 156, No. 4, 01.04.2015, p. 1283-1291.

Research output: Contribution to journalArticle

@article{3ea08d7b324c4bfeb5fda046b008b097,
title = "Nedd4 haploinsufficient mice display moderate insulin resistance, enhanced lipolysis, and protection against high-fat diet-induced obesity",
abstract = "Neural precursor cell expressed developmentally down-regulated protein 4 (Nedd4) is the prototypical protein in the Nedd4 ubiquitin ligase (E3) family, which governs ubiquitin-dependent endocytosis and/or degradation of plasma membrane proteins. Loss of Nedd4 results in embryonic or neonatal lethality in mice and reduced insulin/IGF-1 signaling in embryonic fibroblasts. To delineate the roles of Nedd4 in vivo, we examined the phenotypes of heterozygous knockout mice using a high-fat diet-induced obesity (HFDIO) model. We observed that Nedd4+/- mice are moderately insulin resistant but paradoxically protected against HFDIO. After high-fat diet feeding, Nedd4+/-mice showed less body weight gain, less fat mass, and smaller adipocytes vs the wild type. Despite ameliorated HFDIO, Nedd4+/- mice did not manifest improvement in glucose tolerance vs the wild type in both genders. Nedd4+/- male, but not female, mice displayed significantly lower fasting blood glucose levels and serum insulin levels. Under obesogenic conditions, Nedd4+/- mice displayed elevated stimulated lipolytic activity, primarily through a β2-adrenergic receptor. Combined, these data support novel complex roles for Nedd4 in metabolic regulation involving altered insulin and β-adrenergic signaling pathways.",
author = "Li, {Jing Jing} and Jr, {Robert J.Ferry} and Shiyong Diao and Bingzhong Xue and Suleiman Bahouth and Francesca-Fang Liao",
year = "2015",
month = "4",
day = "1",
doi = "10.1210/en.2014-1909",
language = "English (US)",
volume = "156",
pages = "1283--1291",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "4",

}

TY - JOUR

T1 - Nedd4 haploinsufficient mice display moderate insulin resistance, enhanced lipolysis, and protection against high-fat diet-induced obesity

AU - Li, Jing Jing

AU - Jr, Robert J.Ferry

AU - Diao, Shiyong

AU - Xue, Bingzhong

AU - Bahouth, Suleiman

AU - Liao, Francesca-Fang

PY - 2015/4/1

Y1 - 2015/4/1

N2 - Neural precursor cell expressed developmentally down-regulated protein 4 (Nedd4) is the prototypical protein in the Nedd4 ubiquitin ligase (E3) family, which governs ubiquitin-dependent endocytosis and/or degradation of plasma membrane proteins. Loss of Nedd4 results in embryonic or neonatal lethality in mice and reduced insulin/IGF-1 signaling in embryonic fibroblasts. To delineate the roles of Nedd4 in vivo, we examined the phenotypes of heterozygous knockout mice using a high-fat diet-induced obesity (HFDIO) model. We observed that Nedd4+/- mice are moderately insulin resistant but paradoxically protected against HFDIO. After high-fat diet feeding, Nedd4+/-mice showed less body weight gain, less fat mass, and smaller adipocytes vs the wild type. Despite ameliorated HFDIO, Nedd4+/- mice did not manifest improvement in glucose tolerance vs the wild type in both genders. Nedd4+/- male, but not female, mice displayed significantly lower fasting blood glucose levels and serum insulin levels. Under obesogenic conditions, Nedd4+/- mice displayed elevated stimulated lipolytic activity, primarily through a β2-adrenergic receptor. Combined, these data support novel complex roles for Nedd4 in metabolic regulation involving altered insulin and β-adrenergic signaling pathways.

AB - Neural precursor cell expressed developmentally down-regulated protein 4 (Nedd4) is the prototypical protein in the Nedd4 ubiquitin ligase (E3) family, which governs ubiquitin-dependent endocytosis and/or degradation of plasma membrane proteins. Loss of Nedd4 results in embryonic or neonatal lethality in mice and reduced insulin/IGF-1 signaling in embryonic fibroblasts. To delineate the roles of Nedd4 in vivo, we examined the phenotypes of heterozygous knockout mice using a high-fat diet-induced obesity (HFDIO) model. We observed that Nedd4+/- mice are moderately insulin resistant but paradoxically protected against HFDIO. After high-fat diet feeding, Nedd4+/-mice showed less body weight gain, less fat mass, and smaller adipocytes vs the wild type. Despite ameliorated HFDIO, Nedd4+/- mice did not manifest improvement in glucose tolerance vs the wild type in both genders. Nedd4+/- male, but not female, mice displayed significantly lower fasting blood glucose levels and serum insulin levels. Under obesogenic conditions, Nedd4+/- mice displayed elevated stimulated lipolytic activity, primarily through a β2-adrenergic receptor. Combined, these data support novel complex roles for Nedd4 in metabolic regulation involving altered insulin and β-adrenergic signaling pathways.

UR - http://www.scopus.com/inward/record.url?scp=84926472070&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84926472070&partnerID=8YFLogxK

U2 - 10.1210/en.2014-1909

DO - 10.1210/en.2014-1909

M3 - Article

VL - 156

SP - 1283

EP - 1291

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 4

ER -