Universität zu Köln

Oteng, Antwi-Boasiako ORCID: 0000-0002-4879-065X, Bhattacharya, Asmita ORCID: 0000-0002-5669-8036, Brodesser, Susanne, Qi, Ling ORCID: 0000-0001-8229-0184, Tan, Nguan Soon ORCID: 0000-0003-0136-7341 and Kersten, Sander ORCID: 0000-0003-4488-7734 (2017). Feeding Angptl4(-/-) mice trans fat promotes foam cell formation in mesenteric lymph nodes without leading to ascites. J. Lipid Res., 58 (6). S. 1100 - 1114. BETHESDA: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. ISSN 1539-7262

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Abstract

Angiopoietin-like 4 (ANGPTL4) regulates plasma triglyceride levels by inhibiting LPL. Inactivation of ANG-PTL4 decreases plasma triglycerides and reduces the risk of coronary artery disease. Unfortunately, targeting ANGPTL4 for the therapeutic management of dyslipidemia and atherosclerosis is hampered by the observation that mice and monkeys in which ANGPTL4 is inactivated exhibit lipid accumulation in the mesenteric lymph nodes (MLNs). In mice these pathological events exclusively unfold upon feeding a high saturated FA diet and are followed by an ultimately lethal pro-inflammatory response and chylous ascites. Here, we show that Angptl4(-/-) mice fed a diet rich in trans FAs develop numerous lipid-filled giant cells in their MLNs, yet do not have elevated serum amyloid and haptoglobin, do not exhibit ascites, and survive, unlike Angptl4(-/-) mice fed a saturated FA-rich diet. In RAW264.7 macrophages, the saturated FA, palmitate, markedly increased markers of inflammation and the unfolded protein response, whereas the trans-unsaturated elaidate and the cis-unsaturated oleate had the opposite effect. In conclusion, trans and saturated FAs have very distinct biological effects in macrophages. Furthermore, lipid accumulation in MLNs is uncoupled from activation of an acute-phase response and chylous ascites, suggesting that ANGPTL4 should not be fully dismissed as target for dyslipidemia.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Oteng, Antwi-Boasiako UNSPECIFIED orcid.org/0000-0002-4879-065X UNSPECIFIED Bhattacharya, Asmita UNSPECIFIED orcid.org/0000-0002-5669-8036 UNSPECIFIED Brodesser, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Qi, Ling UNSPECIFIED orcid.org/0000-0001-8229-0184 UNSPECIFIED Tan, Nguan Soon UNSPECIFIED orcid.org/0000-0003-0136-7341 UNSPECIFIED Kersten, Sander UNSPECIFIED orcid.org/0000-0003-4488-7734 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-229257
DOI:	10.1194/jlr.M074278
Journal or Publication Title:	J. Lipid Res.
Volume:	58
Number:	6
Page Range:	S. 1100 - 1114
Date:	2017
Publisher:	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Place of Publication:	BETHESDA
ISSN:	1539-7262
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; CORONARY-HEART-DISEASE; LIPOPROTEIN-LIPASE; CARDIOVASCULAR-DISEASE; ER STRESS; TRIGLYCERIDE-METABOLISM; NLRP3 INFLAMMASOME; RAT HEPATOCYTES; SATURATED FAT Multiple languages Biochemistry & Molecular Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22925