Premium
Neonatal nutrition affects adolescent insulin sensitivity and the lineage allocation of bone marrow derived mesenchymal stem cells in Ossabaw pigs
Author(s) -
Zhang Wei,
Murray Robert,
Stahl Chad
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.31.1
Subject(s) - weaning , calorie , insulin resistance , meal , endocrinology , biology , medicine , obesity , insulin , zoology
The Ossabaw pig is an excellent model for the study of nutritionally‐induced metabolic diseases due to similarities in their physiology and nutrient requirements to those of humans, and their voluntary consumption of excess dietary energy. In this study, we determined the impact of different neonatal feeding strategies on the later‐life development of obesity and insulin resistance. Additionally, we characterized alterations in the lineage allocation of mesenchymal stem cells (MSC) in response to these feeding strategies. Newborn ossabaw pigs were either sow‐reared or formula fed from 24h old until weaning (32.1±0.4 d of age). Sow‐reared pigs were then randomly assigned to either control diet or obesigenic diet. All pigs which received formula were then fed the obesigenic diet. After weaning, pigs were meal fed twice/day. The diets were formulated to provide equal protein, vitamins and minerals among the treatments and to provide 3X more calories in the obesigenic diet. Body weight was recorded weekly for 16 wks. At the end of the feeding study, IV glucose tolerance tests were conducted and MSC isolated. Pigs fed with obesigenic diet had 1.5‐fold heavier body weight than the control at the end of the study (P<0.05). This was coupled with significantly greater body length, neck, chest and waist size in the obesigenic groups. The obesigenic fed pigs had reduced glucose clearance capabilities compared to the control fed pigs. Among the obesigenic fed pigs, those that received formula had 1.7‐fold higher circulating glucose than sow‐reared pigs (P<0.05) and both were 2.8 and 1.6‐fold greater than the control, respectively (P<0.05). No significant difference in insulin area under the curve between the formula‐fed pigs and the sow‐reared pigs with obesigenic diet, while both had 1.9 and 2.1 folder higher insulin area under the curve than the control (P<0.05). The MSC isolated from the obese pigs had a greater ability to differentiate along an osteogenic lineage as observed by increased expression of osteocalcin and fibronectin (osteocalcin: 2.12±0.31 vs 1.04±0.31 and fibronectin: 3.42±0.30 vs 2.30±0.29, P<0.05). This alteration in MSC behavior was mirrored by increased bone size and mineral content (1.2 to 1.5 fold higher than the control (P<0.05). This work demonstrates that neonatal nutritional interventions can impact metabolic susceptibility to obesity, and that excessive dietary energy during pre‐pubertal life alters metabolism at both the systemic and cellular levels.