The apolipoprotein-al mimetic peptide L4F at a modest dose does not attenuate weight gain, inflammation, or atherosclerosis in Ldlr-null mice

Michelle M. Averill, Eung Ju Kim, Leela Goodspeed, Shari Wang, Savitha Subramanian, Laura J.Den Hartigh, Chongren Tang, Yilei Ding, Catherine A. Reardon, Godfrey S. Getz, Alan Chait

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Objective: High density lipoprotein (HDL) cholesterol levels are inversely related to cardiovascular disease risk and associated with a reduced risk of type 2 diabetes. Apolipoprotein A-l (apoA-l; major HDL protein) mimetics have been reported to reduce atherosclerosis and decrease adiposity. This study investigated the effect of L4F mimetic peptide and apoA-I overexpression on weight gain, insulin resistance, and atherosclerosis in an LDL receptor deficient (Ldlr&quot) model fed a high fat high sucrose with cholesterol (HFHSC) diet.

Methods: Studies in differentiated 3T3-L1 adipocytes tested whether L4F could inhibit palmitate-induced adipocyte inflammation. In vivo studies used male Ldir&quotmice fed a HFHSC diet for 12 weeks and were injected daily with L4F (100 μg/ mouse) subcutaneously during the last 8 weeks. Wild-type and apoA-l overexpressing Ldir&qout mice were fed HFHSC diet for 16 weeks.

Results: Neither L4F administration nor apoA-I overexpression affected weight gain, total plasma cholesterol or triglycerides in our studies. While pre-treatment of 3T3-L1 adipocytes with either L4F or HDL abolished palmitate-induced cytokine expression in vitro, L4F treatment did not affect circulating or adipose tissue inflammatory markers in vivo. Neither L4F administration nor apoA-I overexpression affected glucose tolerance. ApoA-l overexpression significantly reduced atherosclerotic lesion size, yet L4F treatment did not affect atherosclerosis.

Conclusion: Out results suggest that neither L4F (100 pg/day/mouse) nor apoA-l overexpression affects adiposity or insulin resistance in this model. We also were unable to confirm a reduction in atherosclerosis with L4F in our particular model. Further studies on the effect of apoA-l mimetics on atherosclerosis and insulin resistance in a variety of dietary contexts are warranted.

Original languageEnglish
Article numbere109252
JournalPLoS One
Volume9
Issue number10
DOIs
Publication statusPublished - 2014 Oct 6
Externally publishedYes

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Apolipoproteins A
apolipoproteins
Apolipoproteins
atherosclerosis
Weight Gain
Atherosclerosis
inflammation
weight gain
peptides
Inflammation
Peptides
adipocytes
cholesterol
insulin resistance
Apolipoprotein A-I
mice
Nutrition
dosage
Cholesterol
Adipocytes

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

The apolipoprotein-al mimetic peptide L4F at a modest dose does not attenuate weight gain, inflammation, or atherosclerosis in Ldlr-null mice. / Averill, Michelle M.; Kim, Eung Ju; Goodspeed, Leela; Wang, Shari; Subramanian, Savitha; Hartigh, Laura J.Den; Tang, Chongren; Ding, Yilei; Reardon, Catherine A.; Getz, Godfrey S.; Chait, Alan.

In: PLoS One, Vol. 9, No. 10, e109252, 06.10.2014.

Research output: Contribution to journalArticle

Averill, MM, Kim, EJ, Goodspeed, L, Wang, S, Subramanian, S, Hartigh, LJD, Tang, C, Ding, Y, Reardon, CA, Getz, GS & Chait, A 2014, 'The apolipoprotein-al mimetic peptide L4F at a modest dose does not attenuate weight gain, inflammation, or atherosclerosis in Ldlr-null mice', PLoS One, vol. 9, no. 10, e109252. https://doi.org/10.1371/journal.pone.0109252
Averill, Michelle M. ; Kim, Eung Ju ; Goodspeed, Leela ; Wang, Shari ; Subramanian, Savitha ; Hartigh, Laura J.Den ; Tang, Chongren ; Ding, Yilei ; Reardon, Catherine A. ; Getz, Godfrey S. ; Chait, Alan. / The apolipoprotein-al mimetic peptide L4F at a modest dose does not attenuate weight gain, inflammation, or atherosclerosis in Ldlr-null mice. In: PLoS One. 2014 ; Vol. 9, No. 10.
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abstract = "Objective: High density lipoprotein (HDL) cholesterol levels are inversely related to cardiovascular disease risk and associated with a reduced risk of type 2 diabetes. Apolipoprotein A-l (apoA-l; major HDL protein) mimetics have been reported to reduce atherosclerosis and decrease adiposity. This study investigated the effect of L4F mimetic peptide and apoA-I overexpression on weight gain, insulin resistance, and atherosclerosis in an LDL receptor deficient (Ldlr&quot) model fed a high fat high sucrose with cholesterol (HFHSC) diet.Methods: Studies in differentiated 3T3-L1 adipocytes tested whether L4F could inhibit palmitate-induced adipocyte inflammation. In vivo studies used male Ldir&quotmice fed a HFHSC diet for 12 weeks and were injected daily with L4F (100 μg/ mouse) subcutaneously during the last 8 weeks. Wild-type and apoA-l overexpressing Ldir&qout mice were fed HFHSC diet for 16 weeks.Results: Neither L4F administration nor apoA-I overexpression affected weight gain, total plasma cholesterol or triglycerides in our studies. While pre-treatment of 3T3-L1 adipocytes with either L4F or HDL abolished palmitate-induced cytokine expression in vitro, L4F treatment did not affect circulating or adipose tissue inflammatory markers in vivo. Neither L4F administration nor apoA-I overexpression affected glucose tolerance. ApoA-l overexpression significantly reduced atherosclerotic lesion size, yet L4F treatment did not affect atherosclerosis.Conclusion: Out results suggest that neither L4F (100 pg/day/mouse) nor apoA-l overexpression affects adiposity or insulin resistance in this model. We also were unable to confirm a reduction in atherosclerosis with L4F in our particular model. Further studies on the effect of apoA-l mimetics on atherosclerosis and insulin resistance in a variety of dietary contexts are warranted.",
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AU - Averill, Michelle M.

AU - Kim, Eung Ju

AU - Goodspeed, Leela

AU - Wang, Shari

AU - Subramanian, Savitha

AU - Hartigh, Laura J.Den

AU - Tang, Chongren

AU - Ding, Yilei

AU - Reardon, Catherine A.

AU - Getz, Godfrey S.

AU - Chait, Alan

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Y1 - 2014/10/6

N2 - Objective: High density lipoprotein (HDL) cholesterol levels are inversely related to cardiovascular disease risk and associated with a reduced risk of type 2 diabetes. Apolipoprotein A-l (apoA-l; major HDL protein) mimetics have been reported to reduce atherosclerosis and decrease adiposity. This study investigated the effect of L4F mimetic peptide and apoA-I overexpression on weight gain, insulin resistance, and atherosclerosis in an LDL receptor deficient (Ldlr&quot) model fed a high fat high sucrose with cholesterol (HFHSC) diet.Methods: Studies in differentiated 3T3-L1 adipocytes tested whether L4F could inhibit palmitate-induced adipocyte inflammation. In vivo studies used male Ldir&quotmice fed a HFHSC diet for 12 weeks and were injected daily with L4F (100 μg/ mouse) subcutaneously during the last 8 weeks. Wild-type and apoA-l overexpressing Ldir&qout mice were fed HFHSC diet for 16 weeks.Results: Neither L4F administration nor apoA-I overexpression affected weight gain, total plasma cholesterol or triglycerides in our studies. While pre-treatment of 3T3-L1 adipocytes with either L4F or HDL abolished palmitate-induced cytokine expression in vitro, L4F treatment did not affect circulating or adipose tissue inflammatory markers in vivo. Neither L4F administration nor apoA-I overexpression affected glucose tolerance. ApoA-l overexpression significantly reduced atherosclerotic lesion size, yet L4F treatment did not affect atherosclerosis.Conclusion: Out results suggest that neither L4F (100 pg/day/mouse) nor apoA-l overexpression affects adiposity or insulin resistance in this model. We also were unable to confirm a reduction in atherosclerosis with L4F in our particular model. Further studies on the effect of apoA-l mimetics on atherosclerosis and insulin resistance in a variety of dietary contexts are warranted.

AB - Objective: High density lipoprotein (HDL) cholesterol levels are inversely related to cardiovascular disease risk and associated with a reduced risk of type 2 diabetes. Apolipoprotein A-l (apoA-l; major HDL protein) mimetics have been reported to reduce atherosclerosis and decrease adiposity. This study investigated the effect of L4F mimetic peptide and apoA-I overexpression on weight gain, insulin resistance, and atherosclerosis in an LDL receptor deficient (Ldlr&quot) model fed a high fat high sucrose with cholesterol (HFHSC) diet.Methods: Studies in differentiated 3T3-L1 adipocytes tested whether L4F could inhibit palmitate-induced adipocyte inflammation. In vivo studies used male Ldir&quotmice fed a HFHSC diet for 12 weeks and were injected daily with L4F (100 μg/ mouse) subcutaneously during the last 8 weeks. Wild-type and apoA-l overexpressing Ldir&qout mice were fed HFHSC diet for 16 weeks.Results: Neither L4F administration nor apoA-I overexpression affected weight gain, total plasma cholesterol or triglycerides in our studies. While pre-treatment of 3T3-L1 adipocytes with either L4F or HDL abolished palmitate-induced cytokine expression in vitro, L4F treatment did not affect circulating or adipose tissue inflammatory markers in vivo. Neither L4F administration nor apoA-I overexpression affected glucose tolerance. ApoA-l overexpression significantly reduced atherosclerotic lesion size, yet L4F treatment did not affect atherosclerosis.Conclusion: Out results suggest that neither L4F (100 pg/day/mouse) nor apoA-l overexpression affects adiposity or insulin resistance in this model. We also were unable to confirm a reduction in atherosclerosis with L4F in our particular model. Further studies on the effect of apoA-l mimetics on atherosclerosis and insulin resistance in a variety of dietary contexts are warranted.

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