A Hierarchical Dynamic Model Used for Investigating Feed Efficiency and Its Relationship with Hepatic Gene Expression in APOE*3-Leiden.CETP Mice

Overview

Journal Physiol Rep

Specialty Physiology

Date 2021 May 1

PMID 33932122

Authors

Xiang Zhang

Yared Paalvast

Yanan Wang

Patrick C N Rensen

Albert K Groen

Affiliations

Soon will be listed here.

Abstract

Background: Feed efficiency (FE) is an important trait for livestock and humans. While the livestock industry focuses on increasing FE, in the current obesogenic society it is more of interest to decrease FE. Hence, understanding mechanisms involved in the regulation of FE and particularly how it can be decreased would help tremendously in counteracting the obesity pandemic. However, it is difficult to accurately measure or calculate FE in humans. In this study, we aimed to address this challenge by developing a hierarchical dynamic model based on humanized mouse data.

Methods: We analyzed existing experimental data derived from 105 APOE*3-Leiden.CETP (E3L.CETP) mice fed a high-fat high-cholesterol (HFHC) diet for 1 (N = 20), 2 (N = 19), 3 (N = 20), and 6 (N = 46) month. We developed an ordinary differential equation (ODE) based model to estimate the FE based on the longitudinal data of body weight and food intake. Since the liver plays an important role in maintaining metabolic homeostasis, we evaluated associations between FE and hepatic gene expression levels. Depending on the feeding duration, we observed different relationships between FE and hepatic gene expression levels.

Results: After 1-month feeding of HFHC diet, we observed that FE was associated with vitamin A metabolism, arachidonic acid metabolism, and the PPAR signaling pathway. After 3- and 6-month feeding of HFHC diet, we observed that FE was associated most strongly with expression levels of Spink1 and H19, genes involved in cell proliferation and glucose metabolism, respectively.

Conclusions: In conclusion, our analysis suggests that various biological processes such as vitamin A metabolism, hepatic response to inflammation, and cell proliferation associate with FE at different stages of diet-induced obesity.

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