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Cited by 127

The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.

Absence of ANGPTL4 in adipose tissue improves glucose tolerance and attenuates atherogenesis

Aryal, Binod, Singh, Abhishek K., Zhang, Xinbo, Varela, Luis, Rotllan, Noemi, Goedeke, Leigh, Chaube, Balkrishna, Camporez, Joao-Paulo, Vatner, Daniel F., Horvath, Tamas L., Shulman, Gerald I., Suárez, Yajaira, Fernández-Hernando, Carlos·2018·JCI Insight
DOI 10.1172/jci.insight.97918PMC PMC5926923
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Abstract

Alterations in ectopic lipid deposition and circulating lipids are major risk factors for developing cardiometabolic diseases. Angiopoietin-like protein 4 (ANGPTL4), a protein that inhibits lipoprotein lipase (LPL), controls fatty acid (FA) uptake in adipose and oxidative tissues and regulates circulating triacylglycerol-rich (TAG-rich) lipoproteins. Unfortunately, global depletion of ANGPTL4 results in severe metabolic abnormalities, inflammation, and fibrosis when mice are fed a high-fat diet (HFD), limiting our understanding of the contribution of ANGPTL4 in metabolic disorders. Here, we demonstrate that genetic ablation of ANGPTL4 in adipose tissue (AT) results in enhanced LPL activity, rapid clearance of circulating TAGs, increased AT lipolysis and FA oxidation, and decreased FA synthesis in AT. Most importantly, we found that absence of ANGPTL4 in AT prevents excessive ectopic lipid deposition in the liver and muscle, reducing novel PKC (nPKC) membrane translocation and enhancing insulin signaling. As a result, we observed a remarkable improvement in glucose tolerance in short-term HFD-fed AT-specific Angptl4 -KO mice. Finally, lack of ANGPTL4 in AT enhances the clearance of proatherogenic lipoproteins, attenuates inflammation, and reduces atherosclerosis. Together, these findings uncovered an essential role of AT ANGPTL4 in regulating peripheral lipid deposition, influencing whole-body lipid and glucose metabolism and the progression of atherosclerosis.

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Crossref · 10.1172/jci.insight.97918

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  • Mice without adipose ANGPTL4 had increased adipose triglyceride deposition and improved glucose tolerance compared with wild-type mice.

    “Two independent studies found that when high-fat diet was fed to mice without adipose ANGPTL4, these mice had increased adipose triglyceride deposition and improved glucose tolerance compared with wild-type mice (31, 32).”

    From Regulation of lipoprotein metabolism by ANGPTL3, ANGPTL4, and ANGPTL8 (2021) · cites this paper as [31]

  • Targeting ANGPTL4 could potentially increase adiposity and increase glucose tolerance, as it does in mice.

    “For example, targeting ANGPTL4 could potentially increase adiposity and increase glucose tolerance, as it does in mice (31–33, 84)”

    From Regulation of lipoprotein metabolism by ANGPTL3, ANGPTL4, and ANGPTL8 (2021) · cites this paper as [31]

  • The effect of increased adipose triglyceride deposition and improved glucose tolerance in mice without adipose ANGPTL4 was lost with chronic (5+ months) high-fat feeding.

    “Interestingly, both studies found that this effect was lost with chronic (5+ mo) of high-fat feeding (31, 32).”

    From Regulation of lipoprotein metabolism by ANGPTL3, ANGPTL4, and ANGPTL8 (2021) · cites this paper as [31]

  • In the absence of ANGPTL4, LPL activity and TG uptake in adipose increases under fasting conditions.

    “Studies with knockout mice confirm that in the absence of ANGPTL4, LPL activity and TG uptake in adipose increases under fasting conditions (31, 32, 63).”

    From Regulation of lipoprotein metabolism by ANGPTL3, ANGPTL4, and ANGPTL8 (2021) · cites this paper as [31]

  • In adipose-specific ANGPTL4 knockout mice, LPL activity is increased in adipose tissue but not in other tissues.

    “In adipose-specific ANGPTL4 knockout mice, LPL activity is increased in adipose tissue but not in other tissues (31, 32),”

    From Regulation of lipoprotein metabolism by ANGPTL3, ANGPTL4, and ANGPTL8 (2021) · cites this paper as [31]

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Research works printed but not linked: 49

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Metadata

Authors
Aryal, B., Singh, A. K., Zhang, X., Varela, L., Rotllan, N., Goedeke, L., Chaube, B., Camporez, J.-P., Vatner, D. F., Horvath, T. L., Shulman, G. I., Suárez, Y., & Fernández-Hernando, C.
Affiliations
  • Vascular Biology and Therapeutics Program,
  • Integrative Cell Signaling and Neurobiology of Metabolism Program, Department of Comparative Medicine,
  • Department of Internal Medicine,
ORCID
Venue
JCI Insight
Publisher
American Society for Clinical Investigation
Published
2018-03-22
Volume
3
Issue
6
ISSN
2379-3708
DOI
10.1172/jci.insight.97918
PMC
PMC5926923
Cited by
127
References
15
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
  • National Heart, Lung, and Blood Institute (R35HL135820, R01HL105945)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK40936)
  • American Heart Association (16EIA27550005, 16GRNT26420047, 17SDG33110002)

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