Loss of SQSTM1/p62 Induces Obesity and Exacerbates Alcohol-Induced Liver Injury in Aged Mice

Hui Qian; Xiaojuan Chao; Shaogui Wang; Yuan Li; Xiaoxiao Jiang; Zhaoli Sun; Thomas Rülicke; Kurt Zatloukal; Hong Min Ni; Wen Xing Ding

doi:10.1016/j.jcmgh.2023.01.016

Loss of SQSTM1/p62 Induces Obesity and Exacerbates Alcohol-Induced Liver Injury in Aged Mice

Hui Qian, Xiaojuan Chao, Shaogui Wang, Yuan Li, Xiaoxiao Jiang, Zhaoli Sun, Thomas Rülicke, Kurt Zatloukal, Hong Min Ni, Wen Xing Ding

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

Background: Alcohol-associated liver disease (ALD) is a worldwide health problem, of which the effective treatment is still lacking. Both detrimental and protective roles of adipose tissue have been implicated in ALD. Although alcohol increases adipose tissue lipolysis to promote alcohol-induced liver injury, alcohol also activates brown adipose tissue (BAT) thermogenesis as an adaptive response in protecting against alcohol-induced liver injury. Moreover, aging and obesity are also risk factors for ALD. In the present study, we investigated the effects of autophagy receptor protein SQSTM1/p62 on adipose tissue and obesity in alcohol-induced liver injury in both young and aged mice. Methods: Young and aged whole-body SQSTM1/p62 knockout (KO) and their age-matched wild-type (WT) mice were subjected to chronic plus binge (Gao-binge) alcohol feeding. Blood, adipose and liver tissues were collected for biochemical and histologic analysis. Results: Aged but not young SQSTM1/p62 KO mice had significantly increased body weight and fat mass compared with the matched WT mice. Gao-binge alcohol feeding induced white adipose atrophy and decreased levels of SQSTM1/p62 levels in adipose tissue in aged WT mice. SQSTM1/p62 KO aged mice were resistant to Gao-binge alcohol-induced white adipose atrophy. Alcohol feeding increased the expression of thermogenic genes in WT mouse BAT, which was significantly blunted in SQSTM1/p62 KO aged mice. Alcohol-fed aged SQSTM1/p62 KO mice showed significantly higher levels of serum alanine aminotransferase, hepatic triglyceride, and inflammation compared with young and aged WT mice fed with alcohol. Alcohol-fed SQSTM1/p62 KO mice also increased secretion of proinflammatory and angiogenic adipokines that may promote alcohol-induced liver injury. Conclusions: Loss of SQSTM1/p62 in aged mice leads to obesity and impairs alcohol-induced BAT adaptation, resulting in exacerbated alcohol-induced liver injury in mice.

Original language	English (US)
Pages (from-to)	1027-1049
Number of pages	23
Journal	CMGH
Volume	15
Issue number	5
DOIs	https://doi.org/10.1016/j.jcmgh.2023.01.016
State	Published - Jan 2023

Keywords

ALD
Adipokine
Adipose Tissue
Autophagy
Steatosis

ASJC Scopus subject areas

Gastroenterology
Hepatology

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10.1016/j.jcmgh.2023.01.016

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@article{8e93deec3ac14c7eaf60d80c3b3244b0,

title = "Loss of SQSTM1/p62 Induces Obesity and Exacerbates Alcohol-Induced Liver Injury in Aged Mice",

abstract = "Background: Alcohol-associated liver disease (ALD) is a worldwide health problem, of which the effective treatment is still lacking. Both detrimental and protective roles of adipose tissue have been implicated in ALD. Although alcohol increases adipose tissue lipolysis to promote alcohol-induced liver injury, alcohol also activates brown adipose tissue (BAT) thermogenesis as an adaptive response in protecting against alcohol-induced liver injury. Moreover, aging and obesity are also risk factors for ALD. In the present study, we investigated the effects of autophagy receptor protein SQSTM1/p62 on adipose tissue and obesity in alcohol-induced liver injury in both young and aged mice. Methods: Young and aged whole-body SQSTM1/p62 knockout (KO) and their age-matched wild-type (WT) mice were subjected to chronic plus binge (Gao-binge) alcohol feeding. Blood, adipose and liver tissues were collected for biochemical and histologic analysis. Results: Aged but not young SQSTM1/p62 KO mice had significantly increased body weight and fat mass compared with the matched WT mice. Gao-binge alcohol feeding induced white adipose atrophy and decreased levels of SQSTM1/p62 levels in adipose tissue in aged WT mice. SQSTM1/p62 KO aged mice were resistant to Gao-binge alcohol-induced white adipose atrophy. Alcohol feeding increased the expression of thermogenic genes in WT mouse BAT, which was significantly blunted in SQSTM1/p62 KO aged mice. Alcohol-fed aged SQSTM1/p62 KO mice showed significantly higher levels of serum alanine aminotransferase, hepatic triglyceride, and inflammation compared with young and aged WT mice fed with alcohol. Alcohol-fed SQSTM1/p62 KO mice also increased secretion of proinflammatory and angiogenic adipokines that may promote alcohol-induced liver injury. Conclusions: Loss of SQSTM1/p62 in aged mice leads to obesity and impairs alcohol-induced BAT adaptation, resulting in exacerbated alcohol-induced liver injury in mice.",

keywords = "ALD, Adipokine, Adipose Tissue, Autophagy, Steatosis",

author = "Hui Qian and Xiaojuan Chao and Shaogui Wang and Yuan Li and Xiaoxiao Jiang and Zhaoli Sun and Thomas R{\"u}licke and Kurt Zatloukal and Ni, {Hong Min} and Ding, {Wen Xing}",

note = "Funding Information: Funding Supported in part by the National Institutes of Health (NIH) funds R01 DK102142 , R01 AG072895 , and R37 AA020518 (WXD). Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = jan,

doi = "10.1016/j.jcmgh.2023.01.016",

language = "English (US)",

volume = "15",

pages = "1027--1049",

journal = "CMGH",

issn = "2352-345X",

publisher = "Elsevier Inc.",

number = "5",

}

TY - JOUR

T1 - Loss of SQSTM1/p62 Induces Obesity and Exacerbates Alcohol-Induced Liver Injury in Aged Mice

AU - Qian, Hui

AU - Chao, Xiaojuan

AU - Wang, Shaogui

AU - Li, Yuan

AU - Jiang, Xiaoxiao

AU - Sun, Zhaoli

AU - Rülicke, Thomas

AU - Zatloukal, Kurt

AU - Ni, Hong Min

AU - Ding, Wen Xing

PY - 2023/1

Y1 - 2023/1

N2 - Background: Alcohol-associated liver disease (ALD) is a worldwide health problem, of which the effective treatment is still lacking. Both detrimental and protective roles of adipose tissue have been implicated in ALD. Although alcohol increases adipose tissue lipolysis to promote alcohol-induced liver injury, alcohol also activates brown adipose tissue (BAT) thermogenesis as an adaptive response in protecting against alcohol-induced liver injury. Moreover, aging and obesity are also risk factors for ALD. In the present study, we investigated the effects of autophagy receptor protein SQSTM1/p62 on adipose tissue and obesity in alcohol-induced liver injury in both young and aged mice. Methods: Young and aged whole-body SQSTM1/p62 knockout (KO) and their age-matched wild-type (WT) mice were subjected to chronic plus binge (Gao-binge) alcohol feeding. Blood, adipose and liver tissues were collected for biochemical and histologic analysis. Results: Aged but not young SQSTM1/p62 KO mice had significantly increased body weight and fat mass compared with the matched WT mice. Gao-binge alcohol feeding induced white adipose atrophy and decreased levels of SQSTM1/p62 levels in adipose tissue in aged WT mice. SQSTM1/p62 KO aged mice were resistant to Gao-binge alcohol-induced white adipose atrophy. Alcohol feeding increased the expression of thermogenic genes in WT mouse BAT, which was significantly blunted in SQSTM1/p62 KO aged mice. Alcohol-fed aged SQSTM1/p62 KO mice showed significantly higher levels of serum alanine aminotransferase, hepatic triglyceride, and inflammation compared with young and aged WT mice fed with alcohol. Alcohol-fed SQSTM1/p62 KO mice also increased secretion of proinflammatory and angiogenic adipokines that may promote alcohol-induced liver injury. Conclusions: Loss of SQSTM1/p62 in aged mice leads to obesity and impairs alcohol-induced BAT adaptation, resulting in exacerbated alcohol-induced liver injury in mice.

AB - Background: Alcohol-associated liver disease (ALD) is a worldwide health problem, of which the effective treatment is still lacking. Both detrimental and protective roles of adipose tissue have been implicated in ALD. Although alcohol increases adipose tissue lipolysis to promote alcohol-induced liver injury, alcohol also activates brown adipose tissue (BAT) thermogenesis as an adaptive response in protecting against alcohol-induced liver injury. Moreover, aging and obesity are also risk factors for ALD. In the present study, we investigated the effects of autophagy receptor protein SQSTM1/p62 on adipose tissue and obesity in alcohol-induced liver injury in both young and aged mice. Methods: Young and aged whole-body SQSTM1/p62 knockout (KO) and their age-matched wild-type (WT) mice were subjected to chronic plus binge (Gao-binge) alcohol feeding. Blood, adipose and liver tissues were collected for biochemical and histologic analysis. Results: Aged but not young SQSTM1/p62 KO mice had significantly increased body weight and fat mass compared with the matched WT mice. Gao-binge alcohol feeding induced white adipose atrophy and decreased levels of SQSTM1/p62 levels in adipose tissue in aged WT mice. SQSTM1/p62 KO aged mice were resistant to Gao-binge alcohol-induced white adipose atrophy. Alcohol feeding increased the expression of thermogenic genes in WT mouse BAT, which was significantly blunted in SQSTM1/p62 KO aged mice. Alcohol-fed aged SQSTM1/p62 KO mice showed significantly higher levels of serum alanine aminotransferase, hepatic triglyceride, and inflammation compared with young and aged WT mice fed with alcohol. Alcohol-fed SQSTM1/p62 KO mice also increased secretion of proinflammatory and angiogenic adipokines that may promote alcohol-induced liver injury. Conclusions: Loss of SQSTM1/p62 in aged mice leads to obesity and impairs alcohol-induced BAT adaptation, resulting in exacerbated alcohol-induced liver injury in mice.

KW - ALD

KW - Adipokine

KW - Adipose Tissue

KW - Autophagy

KW - Steatosis

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DO - 10.1016/j.jcmgh.2023.01.016

M3 - Article

C2 - 36754207

AN - SCOPUS:85150047104

SN - 2352-345X

VL - 15

SP - 1027

EP - 1049

JO - CMGH

JF - CMGH

IS - 5

ER -

Loss of SQSTM1/p62 Induces Obesity and Exacerbates Alcohol-Induced Liver Injury in Aged Mice

Abstract

Keywords

ASJC Scopus subject areas

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