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Altered adipocyte structure and function in nutritionally programmed microswine offspring

Published online by Cambridge University Press:  25 April 2012

E. A. DuPriest ,
P. Kupfer ,
B. Lin ,
K. Sekiguchi ,
T. K. Morgan ,
K. E. Saunders ,
T. T. Chatkupt ,
O. N. Denisenko ,
J. Q. Purnell  and
S. P. Bagby
E. A. DuPriest
Affiliation:
Department of Medicine, Oregon Health & Science University, Portland, OR, USA Department of Physiology & Pharmacology, Oregon Health & Science University, Portland, OR, USA Research Service, Portland VA Medical Center, Portland, OR, USA Department of Natural Sciences and Health, Warner Pacific College, Portland, OR, USA
P. Kupfer
Affiliation:
Department of Medicine, Oregon Health & Science University, Portland, OR, USA Research Service, Portland VA Medical Center, Portland, OR, USA
B. Lin
Affiliation:
Department of Medicine, Oregon Health & Science University, Portland, OR, USA Research Service, Portland VA Medical Center, Portland, OR, USA
K. Sekiguchi
Affiliation:
Department of Medicine, Oregon Health & Science University, Portland, OR, USA Research Service, Portland VA Medical Center, Portland, OR, USA
T. K. Morgan
Affiliation:
Department of Pathology, Oregon Health & Science University, Portland, OR, USA
K. E. Saunders
Affiliation:
Department of Comparative Medicine, Oregon Health & Science University, Portland, OR, USA
T. T. Chatkupt
Affiliation:
Department of Comparative Medicine, Oregon Health & Science University, Portland, OR, USA
O. N. Denisenko
Affiliation:
Department of Medicine, University of Washington, Seattle, WA, USA
J. Q. Purnell
Affiliation:
Department of Medicine, Oregon Health & Science University, Portland, OR, USA
S. P. Bagby*
Affiliation:
Department of Medicine, Oregon Health & Science University, Portland, OR, USA Department of Physiology & Pharmacology, Oregon Health & Science University, Portland, OR, USA Research Service, Portland VA Medical Center, Portland, OR, USA
*
*Address for correspondence: Dr S. P. Bagby, Professor of Medicine & Physiology/Pharmacology, Division of Nephrology & Hypertension, Oregon Health & Science University, 3303 SW Bond Avenue (CH12R), Portland, OR 97239-3098, USA. Email bagbys@ohsu.edu
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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.

Keywords

adipose tissuecatch-up growthmaternal protein restriction
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 3 , Issue 3 , June 2012 , pp. 198 - 209
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2012

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