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Phenotypical heterogeneity in responder (R) and non-responder (NR) male ApoE*3Leiden.CETP mice


Tarasco, Erika; Pellegrini, Giovanni; Whiting, Lynda; Lutz, Thomas A (2018). Phenotypical heterogeneity in responder (R) and non-responder (NR) male ApoE*3Leiden.CETP mice. American Journal Of Physiology. Gastrointestinal And Liver Physiology, 315(4):G602-G617.

Abstract

The metabolic syndrome (MetS) is a major health issue worldwide and is associated with obesity, insulin resistance, and hypercholesterolemia. Several animal models were used to describe the MetS, however many of them do not mimic well the MetS pathophysiology in humans. The ApoE*3Leiden.CETP mouse model overcomes part of this limitation, since they have a humanised lipoprotein metabolism and a heterogeneous response to MetS, similarly to humans. The reported heterogeneity among them and their common classification into responder (R) and non-responder mice (NR); R mice show increased body weight, cholesterol and triglycerides levels, while NR mice do not show this expected phenotype when fed a Western type diet. To better define the differences between R and NR mice, we focused on feeding behavior, body weight gain, glucose tolerance, and lipid parameters, and on an extensive pathological examination along with liver histology analysis. Our data confirmed that R mice resemble the pathological features of the human MetS: obesity, dysplipidemia, glucose intolerance; NR mice do not develop the full dysmetabolic phenotype because of a severe inflammatory hepatic condition, which may heavily affect liver function. We conclude that R and NR mice are metabolically different and that NR mice have indications of severely impaired liver function. Hence, it is critical to identify and separate the respective mice to decrease data heterogeneity. Clinical chemistry and histological analysis should be used to confirm retrospectively the animals' classification. Moreover, we point out that NR mice may not be an appropriate control for studies involving ApoE*3Leiden.CETP R mice.

Abstract

The metabolic syndrome (MetS) is a major health issue worldwide and is associated with obesity, insulin resistance, and hypercholesterolemia. Several animal models were used to describe the MetS, however many of them do not mimic well the MetS pathophysiology in humans. The ApoE*3Leiden.CETP mouse model overcomes part of this limitation, since they have a humanised lipoprotein metabolism and a heterogeneous response to MetS, similarly to humans. The reported heterogeneity among them and their common classification into responder (R) and non-responder mice (NR); R mice show increased body weight, cholesterol and triglycerides levels, while NR mice do not show this expected phenotype when fed a Western type diet. To better define the differences between R and NR mice, we focused on feeding behavior, body weight gain, glucose tolerance, and lipid parameters, and on an extensive pathological examination along with liver histology analysis. Our data confirmed that R mice resemble the pathological features of the human MetS: obesity, dysplipidemia, glucose intolerance; NR mice do not develop the full dysmetabolic phenotype because of a severe inflammatory hepatic condition, which may heavily affect liver function. We conclude that R and NR mice are metabolically different and that NR mice have indications of severely impaired liver function. Hence, it is critical to identify and separate the respective mice to decrease data heterogeneity. Clinical chemistry and histological analysis should be used to confirm retrospectively the animals' classification. Moreover, we point out that NR mice may not be an appropriate control for studies involving ApoE*3Leiden.CETP R mice.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Integrative Human Physiology
05 Vetsuisse Faculty > Institute of Veterinary Physiology
05 Vetsuisse Faculty > Institute of Veterinary Pathology
Dewey Decimal Classification:570 Life sciences; biology
Uncontrolled Keywords:Hepatology, Gastroenterology, Physiology (medical), Physiology, heterogeneity and phenotype; inflammation; liver functionality; metabolic syndromes
Language:English
Date:1 October 2018
Deposited On:21 Aug 2018 17:46
Last Modified:06 Oct 2018 01:02
Publisher:American Physiological Society
ISSN:0193-1857
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1152/ajpgi.00081.2018
PubMed ID:29975550

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Content: Accepted Version
Language: English
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Embargo till: 2019-07-05