Reciprocal Regulation of Hepatic and Adipose Lipogenesis by Liver X Receptors in Obesity and Insulin Resistance

被引：171

作者：

Beaven, Simon W. ^{[1
,2
,3
]}

Matveyenko, Aleksey ^{[4
,5
]}

Wroblewski, Kevin ^{[1
,2
]}

Chao, Lily ^{[1
,2
]}

Wilpitz, Damien ^{[1
,2
]}

Hsu, Tu Wen ^{[4
,5
]}

Lentz, Jacob ^{[3
]}

Drew, Brian ^{[4
]}

Hevener, Andrea L. ^{[4
]}

Tontonoz, Peter ^{[1
,2
]}

机构：

[1] Univ Calif Los Angeles, David Geffen Sch Med, Howard Hughes Med Inst, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Digest Dis, Los Angeles, CA 90095 USA

[4] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Endocrinol Diabet & Hypertens, Los Angeles, CA 90095 USA

[5] Univ Calif Los Angeles, David Geffen Sch Med, Larry Hillblom Islet Res Ctr, Los Angeles, CA 90095 USA

来源：

CELL METABOLISM | 2013年 / 18卷 / 01期

关键词：

STEAROYL-COA DESATURASE-1; NONALCOHOLIC FATTY LIVER; ISLET AMYLOID POLYPEPTIDE; ELEMENT-BINDING PROTEIN; LIPID-METABOLISM; GENE-EXPRESSION; MICE LACKING; LXR-ALPHA; COORDINATE REGULATION; GLUCOSE-METABOLISM;

D O I：

10.1016/j.cmet.2013.04.021

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Liver X receptors (LXRs) regulate lipogenesis and inflammation, but their contribution to the metabolic syndrome is unclear. We show that LXRs modulate key aspects of the metabolic syndrome in mice. LXRab-deficient-ob/ob (LOKO) mice remain obese but show reduced hepatic steatosis and improved insulin sensitivity compared to ob/ob mice. Impaired hepatic lipogenesis in LOKO mice is accompanied by reciprocal increases in adipose lipid storage, reflecting tissue-selective effects on the SREBP, PPAR gamma, and ChREBP lipogenic pathways. LXRs are essential for obesity-driven SREBP-1c and ChREBP activity in liver, but not fat. Furthermore, loss of LXRs in obesity promotes adipose PPARg and ChREBP-beta activity, leading to improved insulin sensitivity. LOKO mice also exhibit defects in beta cell mass and proliferation despite improved insulin sensitivity. Our data suggest that sterol sensing by LXRs in obesity is critically linked with lipid and glucose homeostasis and provide insight into the complex relationships between LXR and insulin signaling.

引用

页码：106 / 117

页数：12

共 68 条

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