Haplotypes on pig chromosome 3 distinguish metabolically healthy from unhealthy obese individuals.

Simona D Frederiksen,Philippe Lesnik,Peter Karlskov-Mortensen,Camilla S Bruun,Claus B Jørgensen,Thomas Mark,Maryse Guerin,Susanna Cirera,Sameer D Pant,Merete Fredholm

doi:10.1371/journal.pone.0178828

Simona D Frederiksen, Philippe Lesnik + Show 8 more

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https://doi.org/10.1371/journal.pone.0178828

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Abstract

We have established a pig resource population specifically designed to elucidate the genetics involved in development of obesity and obesity related co-morbidities by crossing the obesity prone Göttingen Minipig breed with two lean production pig breeds. In this study we have performed genome wide association (GWA) to identify loci with effect on blood lipid levels. The most significantly associated single nucleotide polymorphisms (SNPs) were used for linkage disequilibrium (LD) and haplotype analyses. Three separate haploblocks which influence the ratio between high density lipoprotein cholesterol and total cholesterol (HDL-C/CT), triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) levels respectively were identified on Sus Scrofa chromosome 3 (SSC3). Large additive genetic effects were found for the HDL-C/CT and LDL-C haplotypes. Haplotypes segregating from Göttingen Minipigs were shown to impose a positive effect on blood lipid levels. Thus, the genetic profile of the Göttingen Minipig breed seems to support a phenotype comparable to the metabolic healthy obese (MHO) phenotype in humans.

Highlights

Obesity is defined as excessive accumulation of fat in the body to the extent that it may have a negative effect on health
A moderate genetic correlation was found between Age1 and Age2 both in regard to low-density lipoprotein cholesterol (LDL-C) and high-density lipoproteins (HDL)-C/CT, whereas, for TG there was no correlation between measurements at the two ages
The same loci on Sus Scrofa chromosome 3 (SSC3) are associated with low-density lipoproteins (LDL)-C at Age 1 and Age 2 and the same is true for HDL-C/CT

Summary

Introduction

Obesity is defined as excessive accumulation of fat in the body to the extent that it may have a negative effect on health. According to the World Health Organization (WHO), in 2016 obesity had more than doubled worldwide since 1980. Obesity can be socially stigmatizing, in itself it is not the primary health problem. Rather, it is the co-morbidities such as cardiovascular disease (CVD) and type 2 diabetes (T2D) which pose the major health problems. Common to many of the co-morbidities is an unhealthy metabolic profile with insulin resistance and dyslipidemia characterized by elevated triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) levels and by decreased high-density lipoprotein cholesterol.

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