Glucocorticoids In Combination With a High Fat Diet Increase Acute Phase Proteins and Alters PUFA metabolism in Visceral Adipose Tissue

Adipose tissue is a central player in whole body energy homeostasis. During nutrient excess, energy is stored in adipocytes as triglycerides. The resulting expansion of visceral adipose tissue is a known risk factor for chronic disease and has been shown to be exacerbated by both a high fat diet and chronic glucocorticoid therapy. Acutley, glucocorticoids induce lipolysis and promote adipogenesis. However, chronic exposure results in lipodystrophy, which presents as subcutaneous adipose tissue wasting and expansion of the visceral adipose depots. Furthermore, chronic glucocorticoid exposure alters adipocyte metabolism and adipokine secretion, leading to changes in systemic metabolic function. We seek to identify phenotypical and transcriptional alterations in visceral adipose tissue in response to a combination of chronic glucocorticoids administration and consumption of a high fat “Western” type diet containing a high ratio of omega‐6/omega‐3 polyunsaturated fatty acids. This study used 3‐week‐old C57BL/6 male mice that were weaned onto a high fat diet (HFL) (20% kcal protein, 35% kcal carbohydrate, 45% kcal fat, mostly lard). At 6–7 weeks of age, oral glucocorticoid treatment (Prednisolone) was initiated at a dose of 40 mg/m 2 /day using a vehicle of sweet potato (GC+). Control animals received the vehicle alone (GC‐). Glucocorticoid administration continued daily for 28 days. Body weight was monitored twice a week. Adipose‐associated factors measured included: epididymal fat pad weight, adipocyte morphological changes, and systemic and adipose tissue leptin levels. Glucocorticoid treatment increased adipose tissue weight and adipocyte hypertrophy, despite decreased total body weight gain. Glucocorticoid‐induced transcriptional changes in the epididymal fat pads were determined using the Affymetrics MoGene 2.0 ST array and revealed a total of 250 genes (p=<0.05, fold change (FC) of >±1.5), with 120 genes (48%) upregulated and 130 (52%) down regulated. Dramatically increased transcripts included acute phase proteins (Orm1 [FC=2.03], Orm2 [FC=3.82]) and proteins involved in cellular stress. (Serpinb2 [FC=1.96], UPC3 [FC=1.98], Cryab [FC=2.18] and Hspb7 [FC=3.02]). Lipid metabolism transcripts that were downregulated by glucocorticoid treatment included Fads2 (FC=− 4.19), Isyna1 (FC=−4.14) and Acsbg1 (FC=−1.85). The results presented here include novel findings regarding early transcriptional changes induced in visceral adipose tissue by chronic glucocorticoid treatment when consuming a high fat diet. The genes identified in this study provide opportunities for therapeutic interventions to alter glucocorticoid‐associated metabolic dysfucntions Support or Funding Information University of Memphis Faculty Research grant MvdM start up