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Antioxidants (Basel). 2019 Jan 11;8(1). pii: E19. doi: 10.3390/antiox8010019.

PON2 Deficiency Leads to Increased Susceptibility to Diet-Induced Obesity.

Author information

1
Division of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. DShih@mednet.ucla.edu.
2
Division of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. YMeng@mednet.ucla.edu.
3
Division of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. TSallam@mednet.ucla.edu.
4
Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA. lvergnes@ucla.edu.
5
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA. michellelshu@ucla.edu.
6
Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA. KReue@mednet.ucla.edu.
7
Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. KReue@mednet.ucla.edu.
8
Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. PTontonoz@mednet.ucla.edu.
9
Division of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. AFogelman@mednet.ucla.edu.
10
Division of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. Jlusis@mednet.ucla.edu.
11
Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA. Jlusis@mednet.ucla.edu.
12
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA. Jlusis@mednet.ucla.edu.
13
Division of Cardiology, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. SReddy@mednet.ucla.edu.
14
Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USA. SReddy@mednet.ucla.edu.

Abstract

(1) Background: Paraoxonase 2 (PON2) is a ubiquitously expressed protein localized to endoplasmic reticulum and mitochondria. Previous studies have shown that PON2 exhibits anti-oxidant and anti-inflammatory functions, and PON2-deficient (PON2-def) mice are more susceptible to atherosclerosis. Furthermore, PON2 deficiency leads to impaired mitochondrial function. (2) Methods: In this study, we examined the susceptibility of PON2-def mice to diet-induced obesity. (3) Results: After feeding of an obesifying diet, the PON2-def mice exhibited significantly increased body weight due to increased fat mass weight as compared to the wild-type (WT) mice. The increased adiposity was due, in part, to increased adipocyte hypertrophy. PON2-def mice had increased fasting insulin levels and impaired glucose tolerance after diet-induced obesity. PON2-def mice had decreased oxygen consumption and energy expenditure. Furthermore, the oxygen consumption rate of subcutaneous fat pads from PON2-def mice was lower compared to WT mice. Gene expression analysis of the subcutaneous fat pads revealed decreased expression levels of markers for beige adipocytes in PON2-def mice. (4) Conclusions: We concluded that altered systemic energy balance, perhaps due to decreased beige adipocytes and mitochondrial dysfunction in white adipose tissue of PON2-def mice, leads to increased obesity in these mice.

KEYWORDS:

antioxidant; mitochondrial function; obesity

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