title: Altered adipocyte structure and function in nutritionally programmed microswine offspring.
abstract: Adipose tissue (AT) dysfunction links obesity of any cause with cardiometabolic disease, but whether early-life nutritional deficiency can program adipocyte dysfunction independently of obesity is untested. In 3-5-month-old juvenile microswine offspring exposed to isocaloric perinatal maternal protein restriction (MPR) and exhibiting accelerated prepubertal fat accrual without obesity, we assessed markers of acquired obesity: adiponectin and tumor necrosis factor (TNF)-α messenger ribonucleic acid (mRNA) levels and adipocyte size in intra-abdominal (ABD-AT) and subcutaneous (SC-AT) adipose tissues. Plasma cortisol, leptin and insulin levels were measured in fetal, neonatal and juvenile offspring. In juvenile low-protein offspring (LPO), adipocyte size in ABD-AT was reduced 22% (P = 0.011 v. controls), whereas adipocyte size in SC-AT was increased in female LPO (P = 0.05) and normal in male LPO; yet, adiponectin mRNA in LPO was low in both sexes and in both depots (P < 0.001). Plasma leptin (P = 0.004) and cortisol (P < 0.05) were reduced only in neonatal LPO during MPR. In juveniles, correlations between % body fat and adiponectin mRNA, TNF-α mRNA or plasma leptin were significant in normal-protein offspring (NPO) but absent in LPO. Plasma glucose in juvenile LPO was increased in males but decreased in females (interaction, P = 0.023); plasma insulin levels and insulin sensitivity were unaffected. Findings support nutritional programming of adipocyte size and gene expression and subtly altered glucose homeostasis. Reduced adiponectin mRNA and adipokine dysregulation in juvenile LPO following accelerated growth occurred independently of obesity, adipocyte hypertrophy or inflammatory markers; thus, perinatal MPR and/or growth acceleration can alter adipocyte structure and disturb adipokine homeostasis in metabolically adverse patterns predictive of enhanced disease risk.
authors.affiliation: 1Department of Medicine, Oregon Health & Science University, Portland, OR, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: DuPriest
authors.affiliation: 1Department of Medicine, Oregon Health & Science University, Portland, OR, USA.
authors.forename: P
authors.initials: P
authors.lastname: Kupfer
authors.affiliation: 1Department of Medicine, Oregon Health & Science University, Portland, OR, USA.
authors.forename: B
authors.initials: B
authors.lastname: Lin
authors.affiliation: 1Department of Medicine, Oregon Health & Science University, Portland, OR, USA.
authors.forename: K
authors.initials: K
authors.lastname: Sekiguchi
authors.affiliation: 5Department of Pathology, Oregon Health & Science University, Portland, OR, USA.
authors.forename: T K
authors.initials: TK
authors.lastname: Morgan
authors.affiliation: 6Department of Comparative Medicine, Oregon Health & Science University, Portland, OR, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Saunders
authors.affiliation: 6Department of Comparative Medicine, Oregon Health & Science University, Portland, OR, USA.
authors.forename: T T
authors.initials: TT
authors.lastname: Chatkupt
authors.affiliation: 7Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: O N
authors.initials: ON
authors.lastname: Denisenko
authors.affiliation: 1Department of Medicine, Oregon Health & Science University, Portland, OR, USA.
authors.forename: J Q
authors.initials: JQ
authors.lastname: Purnell
authors.affiliation: 1Department of Medicine, Oregon Health & Science University, Portland, OR, USA.
authors.forename: S P
authors.initials: SP
authors.lastname: Bagby
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