Apolipoprotein A-IV-Deficient Mice in 129/SvJ Background Are Susceptible to Obesity and Glucose Intolerance

Apolipoprotein A-IV (apoA-IV), synthesized by enterocytes, is potentially involved in regulating lipid absorption and metabolism, food intake, and glucose metabolism. In this study, we backcrossed apoA-IV knockout (apoA-IV<sup>−/−</sup>) mice onto the 129/SvJ background for eight generat...

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Main Authors: Fei Wang, Chih-Wei Ko, Jie Qu, Dong Wu, Qi Zhu, Min Liu, Patrick Tso
Format: Article
Language:English
Published: MDPI AG 2023-11-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/15/22/4840
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author Fei Wang
Chih-Wei Ko
Jie Qu
Dong Wu
Qi Zhu
Min Liu
Patrick Tso
author_facet Fei Wang
Chih-Wei Ko
Jie Qu
Dong Wu
Qi Zhu
Min Liu
Patrick Tso
author_sort Fei Wang
collection DOAJ
description Apolipoprotein A-IV (apoA-IV), synthesized by enterocytes, is potentially involved in regulating lipid absorption and metabolism, food intake, and glucose metabolism. In this study, we backcrossed apoA-IV knockout (apoA-IV<sup>−/−</sup>) mice onto the 129/SvJ background for eight generations. Compared to the wild-type (WT) mice, the 129/SvJ apoA-IV<sup>−/−</sup> mice gained more weight and exhibited delayed glucose clearance even on the chow diet. During a 16-week high-fat diet (20% by weight of fat) study, apoA-IV<sup>−/−</sup> mice were more obese than the WT mice, which was associated with their increased food intake as well as reduced energy expenditure and physical activity. In addition, apoA-IV<sup>−/−</sup> mice developed significant insulin resistance (indicated by HOMA-IR) with severe glucose intolerance even though their insulin levels were drastically higher than the WT mice. In conclusion, we have established a model of apoA-IV<sup>−/−</sup> mice onto the 129/SvJ background. Unlike in the C57BL/6J strain, apoA-IV<sup>−/−</sup> 129/SvJ mice become significantly more obese and insulin-resistant than WT mice. Our current investigations of apoA-IV in the 129/SvJ strain and our previous studies in the C57BL/6J strain underline the impact of genetic background on apoA-IV metabolic effects.
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spelling doaj.art-660813fee4884a71bd2bc812b33af32f2023-11-24T14:59:30ZengMDPI AGNutrients2072-66432023-11-011522484010.3390/nu15224840Apolipoprotein A-IV-Deficient Mice in 129/SvJ Background Are Susceptible to Obesity and Glucose IntoleranceFei Wang0Chih-Wei Ko1Jie Qu2Dong Wu3Qi Zhu4Min Liu5Patrick Tso6Norton Healthcare, 4910 Chamberlain Lane, Louisville, KY 40202, USAChroma Medicine, 201 Brookine Ave, Suite 1101, Boston, MA 02215, USAMedpace Reference Laboratories, LLC., 5365 Medpace Way, Cincinnati, OH 45227, USADepartment of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, ChinaDepartment of Pathology and Laboratory Medicine, Metabolic Diseases Institute, University of Cincinnati, 2180 E Galbraith Road, Cincinnati, OH 45237, USADepartment of Pathology and Laboratory Medicine, Metabolic Diseases Institute, University of Cincinnati, 2180 E Galbraith Road, Cincinnati, OH 45237, USADepartment of Pathology and Laboratory Medicine, Metabolic Diseases Institute, University of Cincinnati, 2180 E Galbraith Road, Cincinnati, OH 45237, USAApolipoprotein A-IV (apoA-IV), synthesized by enterocytes, is potentially involved in regulating lipid absorption and metabolism, food intake, and glucose metabolism. In this study, we backcrossed apoA-IV knockout (apoA-IV<sup>−/−</sup>) mice onto the 129/SvJ background for eight generations. Compared to the wild-type (WT) mice, the 129/SvJ apoA-IV<sup>−/−</sup> mice gained more weight and exhibited delayed glucose clearance even on the chow diet. During a 16-week high-fat diet (20% by weight of fat) study, apoA-IV<sup>−/−</sup> mice were more obese than the WT mice, which was associated with their increased food intake as well as reduced energy expenditure and physical activity. In addition, apoA-IV<sup>−/−</sup> mice developed significant insulin resistance (indicated by HOMA-IR) with severe glucose intolerance even though their insulin levels were drastically higher than the WT mice. In conclusion, we have established a model of apoA-IV<sup>−/−</sup> mice onto the 129/SvJ background. Unlike in the C57BL/6J strain, apoA-IV<sup>−/−</sup> 129/SvJ mice become significantly more obese and insulin-resistant than WT mice. Our current investigations of apoA-IV in the 129/SvJ strain and our previous studies in the C57BL/6J strain underline the impact of genetic background on apoA-IV metabolic effects.https://www.mdpi.com/2072-6643/15/22/4840Apolipoprotein A-IV129/SvJ micefood intakeobesityglucose intolerance
spellingShingle Fei Wang
Chih-Wei Ko
Jie Qu
Dong Wu
Qi Zhu
Min Liu
Patrick Tso
Apolipoprotein A-IV-Deficient Mice in 129/SvJ Background Are Susceptible to Obesity and Glucose Intolerance
Nutrients
Apolipoprotein A-IV
129/SvJ mice
food intake
obesity
glucose intolerance
title Apolipoprotein A-IV-Deficient Mice in 129/SvJ Background Are Susceptible to Obesity and Glucose Intolerance
title_full Apolipoprotein A-IV-Deficient Mice in 129/SvJ Background Are Susceptible to Obesity and Glucose Intolerance
title_fullStr Apolipoprotein A-IV-Deficient Mice in 129/SvJ Background Are Susceptible to Obesity and Glucose Intolerance
title_full_unstemmed Apolipoprotein A-IV-Deficient Mice in 129/SvJ Background Are Susceptible to Obesity and Glucose Intolerance
title_short Apolipoprotein A-IV-Deficient Mice in 129/SvJ Background Are Susceptible to Obesity and Glucose Intolerance
title_sort apolipoprotein a iv deficient mice in 129 svj background are susceptible to obesity and glucose intolerance
topic Apolipoprotein A-IV
129/SvJ mice
food intake
obesity
glucose intolerance
url https://www.mdpi.com/2072-6643/15/22/4840
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