Pre-weaning Growth Hormone Treatment Ameliorates Adipose Tissue Insulin Resistance and Inflammation in Adult Male Offspring Following Maternal Undernutrition

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 649-677-Adipocyte Biology
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-671
Clare Marie Reynolds*, Minglan Li, Clint Gray and Mark Hedley Vickers
University of Auckland, Auckland, New Zealand
Obesity and metabolic dysfunction are key features observed in the offspring of undernourished mothers. While it is clear that obesity gives rise to a state of chronic low-grade inflammation, there is little evidence regarding the role of inflammatory processes in the adipose tissue of undernourished offspring. Growth hormone (GH) is known to exert beneficial effects on fat mass and has anti-inflammatory properties. The present study therefore examined the effect of maternal undernutrition on adipose tissue inflammation in adult offspring and whether treatment with GH during a critical period of developmental plasticity could ameliorate the metabolic dysfunction associated with a poor start to life. Female Sprague-Dawley rats were assigned to either a standard diet (Con) or undernourished (50% of ad libitum; UN) throughout gestation. At postnatal day 3, male Con and UN pups received either saline (ConS, UNS) or GH (2.5µg/g/d) (ConGH, UNGH) by daily subcutaneous injection until day 21. All post-weaning offspring were fed the standard diet ad-libitum until postnatal day 160 when gonadal fat pads were excised. UN offspring displayed significant adipocyte hypertrophy compared to CON offspring which was corrected by early life GH treatment. Adipose explant insulin sensitivity was monitored by glucose uptake assay and cytokine expression and secretion by ELISA and RT-PCR. An ex-vivo glucose uptake assay demonstrated that adipose tissue from UNS offspring had attenuated insulin-stimulated glucose uptake compared to ConS, ConGH and UNGH. This was accompanied by reduced adipose tissue GLUT4 and IRS1 expression. Furthermore enhanced TNF-α and IL-1β secretion from adipose and stromal vascular fraction (SVF) culture was accompanied by increased adipose tissue expression of several key inflammatory genes (MCP-1, IL-1β and NLRP3) along with markers of macrophage infiltration (CD11c and CD68) was observed in UNS compared to ConS, ConGH and UNGH groups. This study demonstrated that UNS offspring display a more potent adipose tissue immunophenotype, correlating with decreased insulin sensitivity. Additionally pre-weaning treatment with GH negates these effects indicating a potential role in the reversal of maternal UN induced metabolic dysfunction.

Nothing to Disclose: CMR, ML, CG, MHV

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Sources of Research Support: Gravida, National centre for growth and development