A sequence variant in the diacylglycerol O-acyltransferase 2 gene influences palmitoleic acid content in pig muscle

Abstract

The bulk of body fat in mammals is in the form of triacylglycerol. Diacylglycerol O-acyltransferase 2 (DGAT2) catalyses the terminal step in triacylglycerol synthesis. The proximity of DGAT2 with stearoyl-CoA desaturase (SCD) in the endoplasmic reticulum may facilitate provision of de novo SCD-mediated fatty acids as substrate for DGAT2. Here, we first searched for sequence variants in the DGAT2 gene to then validate their effect on fat content and fatty acid composition in muscle, subcutaneous fat and liver of 1129 Duroc pigs. A single nucleotide polymorphism in exon 9 (ss7315407085 G > A) was selected as a tag variant for the 33 sequence variants identified in the DGAT2 region. The DGAT2-G allele increased DGAT2 expression in muscle and had a positive impact on muscular C14 and C16 fatty acids at the expense of C18 fatty acids. Although there was no evidence for an interaction of DGAT2 with functional SCD genotypes, pigs carrying the DGAT2-G allele had proportionally more palmitoleic acid relative to palmitic acid. Our findings indicate that DGAT2 preferentially uptakes shorter rather than longer-chain fatty acids as substrate, especially if they are monounsaturated, and confirm that fatty acid metabolism in pigs is subjected to subtle tissue-specific genetic regulatory mechanisms.

Identification of a missense variant in the porcine AGPAT gene family that affects intramuscular fat content through whole-genome sequencing

“…However, there were no clear interactions between AGPAT5 and SCD despite that both genes affect MUFA. Even though the AGPAT5 gene intervenes in the same metabolic pathway as DGAT2, in a previous study we found no effect of DGAT2 on IMF (Solé et al, 2021) and therefore the interaction of these two genes for IMF seems unlikely. In contrast, DGAT2 has a specific effect on intramuscular C16:1n-7 (Solé et al, 2021) but we did not detect any effect of AGPAT5 on this fatty acid.…”

“…All pigs were also genotyped for SNPs in genes SCD (rs80912566, C>T, on SSC14) and LEPR (rs709596309, C>T, on SSC6) following the protocols described in (Estany et al, 2014;Solé et al, 2022) and (Ros-Freixedes et al, 2016), respectively. In a subset of 807 pigs, the genotype for DGAT2 (ss7315407085, G>A, on SSC9) was also available (Solé et al, 2021).…”

“…A typical criterion for prioritizing candidate variants is to limit the search to coding and promoter regions, since the prediction of the potential effects of variants located in non-coding regions from DNA sequence is not straightforward (Johnsson and Jungnickel, 2021). However, in some instances non-coding variants, which may have regulatory functions, have been proposed as candidate variants (Van Laere et al, 2003;Ryan et al, 2012;Solé et al, 2021), while variants in coding regions have often been found to have a small impact on complex traits (Koufariotis et al, 2018;Xiang et al, 2019).…”

Overexpression of DGAT2 Stimulates Lipid Droplet Formation and Triacylglycerol Accumulation in Bovine Satellite Cells

“…SCD1 and DGAT2 are located in close proximity to the endoplasmic reticulum, and SCD has been proposed to mediate the conversion of de novo MUFA to DGAT2 as a substrate for TAG synthesis [ 28 ]. Solé et al [ 29 ] showed that DGAT2 preferentially uptakes shorter rather than longer-chain fatty acids as a substrate, especially if they are monounsaturated. Numerous studies have shown that low DGAT2 expression leads to reduced TAG content.…”

Identification of a missense variant in the porcine AGPAT gene family associated with intramuscular fat content through whole‐genome sequencing

“…A typical criterion for prioritizing candidate variants is to limit the search to coding and promoter regions, since the prediction of the potential effects of variants located in non-coding regions from DNA sequence is not straightforward (Johnsson & Jungnickel, 2021). However, in some instances non-coding variants, which may have regulatory functions, have been proposed as candidate variants (Ryan et al, 2012;Solé et al, 2021;Van Laere et al, 2003), while variants in coding regions have often been found to have a small impact on complex traits Abbreviations: C16:0, palmitic acid; C18:0, stearic acid; C16:1n-7, palmitoleic acid; C18:1n-7, vaccenic acid; C18:1n-9, oleic acid; C18:2n-6, linoleic acid; C18:3n-3, linolenic acid; C20:4n-6, arachidonic acid; MUFA, monounsaturated fatty acids; PUFA, polyunsaturated fatty acids; SFA, saturated fatty acids.…”