Rosiglitazone Reverses Inflammation in Epididymal White Adipose Tissue in Hormone-Sensitive Lipase-Knockout Mice

被引：7

作者：

Kotzbeck, Petra ^{[1
,2
,3
,4
]}

Taschler, Ulrike ^{[2
]}

Haudum, Christoph ^{[1
]}

Foessl, Ines ^{[1
]}

Schoiswohl, Gabriele ^{[5
]}

Boulgaropoulos, Beate ^{[1
,6
]}

Bounab, Kaddour ^{[1
]}

Einsiedler, Johanna ^{[1
]}

Pajed, Laura ^{[2
]}

Tilp, Anna ^{[2
]}

Schwarz, Anna ^{[3
,4
]}

Eichmann, Thomas O. ^{[2
,7
]}

Obermayer-Pietsch, Barbara ^{[1
]}

Giordano, Antonio ^{[8
]}

Cinti, Saverio ^{[8
]}

Zechner, Rudolf ^{[2
,9
]}

Pieber, Thomas R. ^{[1
,6
,9
]}

机构：

[1] Med Univ Graz, Div Endocrinol & Diabetol, Graz, Austria

[2] Karl Franzens Univ Graz, Inst Mol Biosci, Graz, Austria

[3] Med Univ Graz, Dept Surg, Div Plast Aesthet & Reconstruct Surg, Res Unit Tissue Regenerat Repair & Reconstruct, Graz, Austria

[4] Joanneum Res Forsch Gesell mbH, Cooperat Ctr Regenerat Med COREMED, Graz, Austria

[5] Karl Franzens Univ Graz, Dept Pharmacol & Toxicol, Graz, Austria

[6] Joanneum Res Forsch Gesell mbH, Inst Biomed & Hlth Sci HEALTH, Graz, Austria

[7] BioTechMed Graz, Ctr Explorat Lipid, Graz, Austria

[8] Univ Ancona, Ctr Obes, Dept Expt & Clin Med, Politecn Marche, Ancona, Italy

[9] BioTechMed Graz, Graz, Austria

来源：

JOURNAL OF LIPID RESEARCH | 2023年 / 64卷 / 01期

基金：

奥地利科学基金会;

关键词：

adipocytes; adipose tissue; lipolysis; FA metabolism; lipase; inflammation; dysfunctional adipocytes; FA; electron microscopy; lipotoxicity; ENDOPLASMIC-RETICULUM STRESS; INSULIN-RESISTANCE; ER STRESS; MUSCLE; ACCUMULATION; EXPRESSION; DEFICIENCY; METABOLISM; OBESITY; 3T3-L1;

D O I：

10.1016/j.jlr.2022.100305

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Hormone-sensitive lipase (HSL) plays a crucial role in intracellular lipolysis, and loss of HSL leads to diacylglycerol (DAG) accumulation, reduced FA mobilization, and impaired PPAR7 signaling. Hsl knockout mice exhibit adipose tissue inflammation, but the underlying mechanisms are still not clear. Here, we investigated if and to what extent HSL loss contributes to endoplasmic reticulum (ER) stress and adipose tissue inflammation in Hsl knockout mice. Furthermore, we were interested in how impaired PPAR7 signaling affects the development of inflam-mation in epididymal white adipose tissue (eWAT) and inguinal white adipose tissue (iWAT) of Hsl knockout mice and if DAG and ceramide accumula-tion contribute to adipose tissue inflammation and ER stress. Ultrastructural analysis showed a markedly dilated ER in both eWAT and iWAT upon loss of HSL. In addition, Hsl knockout mice exhibited macrophage infiltration and increased F4/80 mRNA expression, a marker of macrophage activation, in eWAT, but not in iWAT. We show that treatment with rosiglitazone, a PPAR7 agonist, attenuated macrophage infiltration and ameliorated inflamma-tion of eWAT, but expression of ER stress markers remained unchanged, as did DAG and ceramide levels in eWAT. Taken together, we show that HSL loss promoted ER stress in both eWAT and iWAT of Hsl knockout mice, but inflammation and macrophage infiltration occurred mainly in eWAT. Also, PPAR7 activation reversed inflammation but not ER stress and DAG accumulation. These data indicate that neither reduction of DAG levels nor ER stress contribute to the reversal of eWAT inflammation in Hsl knockout mice.

引用

页数：12