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.

Accelerated growth without prepubertal obesity in nutritionally programmed microswine offspring

“…The experiment was concluded by terminal harvest of selected organs and tissues from anesthetized well-perfused juvenile offspring, as described below for fetal and neonatal offspring, at 3–5 months of age in an age-matched manner. This harvest protocol is described in detail in a forthcoming manuscript 2 Table 1 Maternal diet composition …”

“…Poor fetal growth is associated with increased risk of metabolic and cardiovascular disease later in life. [1][2][3][4][5][6] Accelerated prepubertal growth amplifies these risks. 7,8 However, it is unclear from retrospective epidemiological studies whether accelerated prepubertal growth reflects nutritional programming alone or additionally requires enriched postnatal diets to promote metabolic or cardiovascular disease in adulthood.…”

“…The present report addresses basic model features at birth and postnatal patterns of growth, feed intake and body composition; a forthcoming report addresses structure and function of adipose tissue, as well as glucocorticoid status in the same offspring. 2…”

“…These offspring were studied serially from birth to prepuberty (3–5 months of age at harvest) to determine whether and how MPR programs postnatal growth, adiposity, adipose tissue structure/function, glucocorticoid system function and/or vascular function. The present report addresses basic model features at birth and postnatal patterns of growth, feed intake and body composition; a forthcoming report addresses structure and function of adipose tissue, as well as glucocorticoid status in the same offspring 2 …”

Altered vertebral and femoral bone structure in juvenile offspring of microswine subject to maternal low protein nutritional challenge

“…At~4 weeks of age, piglets were weaned to ad libitum or calorie-restricted diets (see below). Data from these animals have been previously published (DuPriest et al 2012a(DuPriest et al ,b, 2018.…”