Depot and sex-specific implications for adipose tissue expandability and functional traits in adulthood of late prenatal and early postnatal malnutrition in a precocial sheep model.

Sharmila Ahmad,Rajan Dhakal,Morteza Mansouryar,Prabhat Khanal,Mette Olaf Nielsen,Lise Kirstine Lyngman,Jørgen Steen Agerholm

doi:10.14814/phy2.14600

Sharmila Ahmad, Rajan Dhakal + Show 5 more

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https://doi.org/10.14814/phy2.14600

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Abstract

The aim was to investigate long‐term, tissue and sex‐specific impacts of pre and postnatal malnutrition on expandability and functional traits of different adipose tissues. Twin‐pregnant ewes were fed NORM (~requirements), LOW (50% of NORM) or HIGH (150%/110% of energy/protein) diets the last 6 weeks prepartum (term ~147‐days). Lambs received moderate, low‐fat (CONV) or high‐carbohydrate‐high‐fat (HCHF) diets from 3 days until 6 months of age, and thereafter CONV diet. At 2½ years of age (adulthood), histomorphometric and gene expression patterns were characterized in subcutaneous (SUB), perirenal (PER), mesenteric (MES), and epicardial (EPI) adipose tissues. SUB had sex‐specific (♂<♀) upper‐limits for adipocyte size and cell‐number indices, irrespective of early life nutrition. PER mass and contents of adipocytes were highest in females and HIGH♂, whereas adipocyte cross‐sectional area was lowest in LOW♂. Pre/postnatal nutrition affected gene expression sex‐specifically in SUB + PER, but unrelated to morphological changes. In PER, LOW/LOW♂ were specific targets of gene expression changes. EPI was affected by postnatal nutrition, and HCHF sheep had enlarged adipocytes and upregulated expressions for adipogenic and lipogenic genes. Conclusion: upper‐limits for SUB expandability were markedly lower in males. Major targets for prenatal malnutrition were PER and males. LOW♂ had the lowest PER expandability, whereas HIGH♂ had an adaptive advantage due to increased hypertrophic ability equivalent to females. Fixed expandability in SUB meant PER became a determining factor for MES and ectopic fat deposition, rendering LOW♂ particularly predisposed for obesity‐associated metabolic risks. EPI, in contrast to other tissues, was targeted particularly by early postnatal obesity, resulting in adipocyte hypertrophy in adulthood.

Highlights

Pre and postnatal malnutrition have distinct impacts on key metabolic organs (Guan et al, 2005; Long et al, 2015) and adverse consequences for health during the entire lifespan
LOW sheep were born with lower birth weights compared to HIGH and NORM sheep (Khanal et al, 2020)
Compared to NORM, LOW as well as HIGH sheep deposited a greater amount of fat in MES and PER than SUB, when they became obese as adolescents upon exposure to the HCHF diet (Khanal et al, 2020)

Summary

Introduction

Pre and postnatal malnutrition have distinct impacts on key metabolic organs (Guan et al, 2005; Long et al, 2015) and adverse consequences for health during the entire lifespan. We have previously shown that both maternal over- and undernutrition (HIGH and LOW, respectively) during late gestation alter fat deposition patterns as well as adipose gene expression patterns in adolescent sheep and rats (Khanal et al, 2014, 2020; Kjaergaard et al, 2017; Nielsen et al, 2013). This could be ascribed to suppressed expandability of subcutaneous adipose tissue (SUB), resulting in a predisposition for visceral adiposity upon early postnatal development of obesity. But not hyperplasia, is most often associated with the occurrence of metabolic disturbances by inducing the expression of pro-inflammatory cytokines such as interleukins (ILs)-6/8 and monocyte chemoattractant protein-1 (MCP1), predisposing for adipose tissue inflammation (reviewed in Choe et al 2016)

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