Maternal nutrient restriction during pregnancy differentially alters the unfolded protein response in adipose and renal tissue of obese juvenile offspring.
Maternal diet during pregnancy can program an offspring's risk of disease in later life. Obesity adversely alters renal and adipose tissue function, resulting in chronic kidney disease and insulin resistance, respectively, the latter associated with dysregulation of the unfolded protein response (UPR). In view of the current obesity epidemic, we explored the combined effects of in utero early- to midgestational nutrient restriction and postnatal obesity on the UPR in ovine juvenile offspring. Nutrient restriction was coincident with fetal kidney development but prior to exponential adipose tissue deposition. Nutrient restricted (NR) and normal diet (control) offspring were exposed to an obesogenic environment throughout adolescence, resulting in similar degrees of juvenile obesity. NR offspring showed enhanced adipose tissue dysregulation characterized by activation of the UPR, perturbed insulin signaling, and marked inflammation, as demonstrated by increased abundance of crownlike structures and proinflammatory genes. Conversely, in renal tissue NR offspring had marked attenuation of cellular stress and inflammation evident as reduced activation of the UPR, down-regulation of proinflammatory genes, and less histological damage. In conclusion, obesity-related activation of the UPR can be determined by the in utero nutritional environment, demonstrating organ-specific effects dependent on the developmental phase targeted within the fetus.
Sharkey
Don
D
Centre for Reproduction and Early Life, Institute of Clinical Research, University of Nottingham, Nottingham, UK.
Gardner
David S
DS
Fainberg
Hernan P
HP
Sébert
Sylvain
S
Bos
Petra
P
Wilson
Vicky
V
Bell
Rhonda
R
Symonds
Michael E
ME
Budge
Helen
H
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D031204:Caloric Restriction; D005260:Female; D007333:Insulin Resistance; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D039382:Maternal Nutritional Physiological Phenomena; D008928:Mitochondria / Q000648:ultrastructure; D009393:Nephritis / Q000503:physiopathology; D009765:Obesity / Q000209:etiology / Q000235:genetics*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D017510:Protein Folding; D012756:Sheep
D048031:JNK Mitogen-Activated Protein Kinases