Genomic Analysis of Visceral Fat Accumulation in Holstein Cows.

Larissa C Novo,Pedro Melendez,Ligia Cavani,Francisco Peñagaricano,Pablo Pinedo

doi:10.3389/fgene.2021.803216

Abstract

Visceral fat is related to important metabolic processes, including insulin sensitivity and lipid mobilization. The goal of this study was to identify individual genes, pathways, and molecular processes implicated in visceral fat deposition in dairy cows. Data from 172 genotyped Holstein cows classified at slaughterhouse as having low (n = 77; omental fold 5 mm in thickness and minimum fat deposition in omentum) or high (n = 95; omental fold 20 mm in thickness and marked fat deposition in omentum) omental fat were analyzed. The identification of regions with significant additive and non-additive genetic effects was performed using a two-step mixed model-based approach. Genomic scans were followed by gene-set analyses in order to reveal the genetic mechanisms controlling abdominal obesity. The association mapping revealed four regions located on BTA19, BTA20 and BTA24 with significant additive effects. These regions harbor genes, such as SMAD7, ANKRD55, and the HOXB family, that are implicated in lipolysis and insulin tolerance. Three regions located on BTA1, BTA13, and BTA24 showed marked non-additive effects. These regions harbor genes MRAP, MIS18A, PRNP and TSHZ1, that are directly implicated in adipocyte differentiation, lipid metabolism, and insulin sensitivity. The gene-set analysis revealed functional terms related to cell arrangement, cell metabolism, cell proliferation, cell signaling, immune response, lipid metabolism, and membrane permeability, among other functions. We further evaluated the genetic link between visceral fat and two metabolic disorders, ketosis, and displaced abomasum. For this, we analyzed 28k records of incidence of metabolic disorders from 14k cows across lactations using a single-step genomic BLUP approach. Notably, the region on BTA20 significantly associated with visceral fat deposition was also associated with the incidence of displaced abomasum. Overall, our findings suggest that visceral fat deposition in dairy cows is controlled by both additive and non-additive effects. We detected at least one region with marked pleiotropic effects affecting both visceral fat accumulation and displaced abomasum.

Highlights

Fat deposition occurs essentially in three regions, namely intramuscular, subcutaneous, and around visceral organs
The significant region detected in BTA20 (22.88–23.18 Mb) harbors the gene ANKRD55, which is related to adipocyte proliferation and lipolysis
We performed an integrative genomic analysis to better understand the genetic basis of visceral fat accumulation in Holstein cows

Summary

Introduction

Fat deposition occurs essentially in three regions, namely intramuscular, subcutaneous, and around visceral organs These fat depots defer in structural organization, cellular size, biological function, and immunological and metabolic characteristics. Dairy cows typically experience a state of negative energy balance around parturition and early lactation, when the energy demand for maintenance and milk production exceeds that of dietary energy intake (Pascottini et al, 2020). This negative energy balance leads to fat mobilization, and an increase in plasma concentrations of non-esterified fatty acids (NEFA), which are used as a fuel source by peripheral tissues and the mammary gland for milk fat synthesis. Displacement of the abomasum, a condition in which the abomasum becomes enlarged with fluid and gas with subsequent migration to the left or right within the abdominal cavity, results in reduced rumination, decreased milk production, increased veterinary costs, and premature culling

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