Comparative Analysis of Gene Expression Profiles in the Adipose Tissue of Obese Adult Mice With Rapid Infantile Growth After Undernourishment In Utero.

Misako Suzuki,Hiroaki Itoh,Toshiyuki Uchida,Toshiya Itoh,Masako Matsumoto,Naomi Furuta-Isomura,Megumi Ueda,Yukiko Kohmura-Kobayashi,Naoaki Tamura,Megumi Narumi,Tomoaki Oda,Kazuki Mochizuki,Madoka Matsuya,Kenta Kawai

doi:10.3389/fendo.2022.818064

Misako Suzuki, Hiroaki Itoh + Show 12 more

Open Access

https://doi.org/10.3389/fendo.2022.818064

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Abstract

Rapid infantile growth (RG) markedly increases the risk of obesity and metabolic disorders in adulthood, particularly among neonates born small. To elucidate the molecular mechanisms by which RG following undernourishment in utero (UN) contributes to the deterioration of adult fat deposition, we developed a UN mouse model using maternal energy restriction, followed by RG achieved by adjustments to 4 pups per litter soon after birth. A high-fat diet (HFD) was fed to weaned pups treated or not (Veh) with tauroursodeoxycholic acid (TU). UN-RG pups showed the deterioration of diet-induced obesity and fat deposition, which was ameliorated by TU. We performed a microarray analysis of epididymal adipose tissue and two gene enrichment analyses (NN-Veh vs UN-RD-Veh and UN-RG-Veh vs UN-RG-TU). The results obtained identified 4 common gene ontologies (GO) terms of inflammatory pathways. In addition to the inflammatory characteristics of 4 GO terms, the results of heatmap and principal component analyses of the representative genes from 4 GO terms, genes of interest (GOI; Saa3, Ubd, S100a8, Hpx, Casp1, Agt, Ptgs2) selected from the 4 GO terms, and immunohistochemistry of macrophages collectively suggested the critical involvement of inflammation in the regulation of fat deposition in the responses to UN and TU. Therefore, the present results support the ‘Developmental Origins of Metaflammation’, the last word of which was recently proposed by the concept of metabolic disorders induced by low-grade systemic inflammation.

Highlights

We are in the midst of a worldwide obesity epidemic
Similar results were observed for epididymal adipose tissue weight (UN-Rapid infantile growth (RG)-tauroursodeoxycholic acid (TU) vs UN-RG-vehicle distilled water (Veh)) (Figure 3D)
Increasing evidence supports RG being causatively associated with obesity and/or metabolic syndrome in later life, in neonates born small [6,7,8,9,10]; the benefits of RG for later neurodevelopment supports its encouragement in infants born preterm [10]

Summary

Introduction

We are in the midst of a worldwide obesity epidemic. The global prevalence of obesity has doubled since 1980 [1] and is an international public health issue [2]. Singhal et al (2017) reported that growth acceleration in healthy infants born at term (either normal or small for gestation) may be associated with an increased longterm risk of obesity and NCDs; the benefits of rapid infant weight gain for later neurodevelopment supports its encouragement in infants born preterm [10]. These findings led us to the concept that rapid infantile growth (RG) in term newborns, with low-birth weights, is causatively associated with a predisposition to obesity and metabolic syndrome in later life. We hypothesized the presence of specific pattens in gene expression profiles of the adipose tissue of pups with RG and undernutrition in utero (UN)

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