title: Preweaning growth hormone treatment ameliorates adipose tissue insulin resistance and inflammation in adult male offspring following maternal undernutrition.
abstract: It is well established that early-life nutritional alterations lead to increased risk of obesity and metabolic disorders in adult life. Although it is clear that obesity gives rise to chronic low-grade inflammation, there is little evidence regarding the role of inflammation in the adipose tissue of undernourished (UN) offspring. GH reduces fat mass and has antiinflammatory properties. The present study examined the effect of maternal UN on adipose inflammation in adult offspring and whether GH treatment during a critical period of developmental plasticity could ameliorate metabolic dysfunction associated with a poor start to life. Sprague Dawley rats were assigned to chow (C) or UN (50% ad libitum; UN) diet throughout gestation. Male C and UN pups received saline (control saline [CS]/UN) or GH (2.5 μg/g/d; control growth hormone [CGH]/undernourished growth hormone [UNGH]) from days 3-21. Postweaning males were further randomized and fed either chow or high-fat diet until day 160. An ex vivo glucose uptake assay demonstrated adipose tissue from UN offspring displayed attenuated insulin-stimulated glucose uptake compared with CS, CGH, and UNGH. This was associated with increased insulin receptor, glucose transporter 4, and insulin receptor substrate 1 gene expression. Furthermore, UN demonstrated enhanced TNFα and IL-1β secretion from adipose explants and stromal vascular fraction cultures accompanied by increased adipose tissue gene expression of several key proinflammatory genes and markers of macrophage infiltration. Overall, UN offspring displayed a more potent immunophenotype, which correlated with decreased insulin sensitivity. Preweaning GH treatment negates these detrimental effects, indicating the potential for reversing metabolic dysfunction in UN adult offspring.
authors.affiliation: Liggins Institute and Gravida, National Research Centre for Growth and Development, University of Auckland, Auckland 1023, New Zealand.
authors.forename: C M
authors.initials: CM
authors.lastname: Reynolds
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.forename: C
authors.initials: C
authors.lastname: Gray
authors.forename: M H
authors.initials: MH
authors.lastname: Vickers
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D000831:Animals, Newborn; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D059305:Diet, High-Fat; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D051275:Glucose Transporter Type 4 / Q000235:genetics; D013006:Growth Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control*; D007328:Insulin / Q000097:blood; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics; D007333:Insulin Resistance; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D011247:Pregnancy; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014886:Weaning
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D051275:Glucose Transporter Type 4; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; C495694:Slc2a4 protein, rat; D013006:Growth Hormone; D011972:Receptor, Insulin