Endocrine Abstracts (2009) 19 P133

Adrenal hypertrophy occurs in concert with insulin resistance following high fat feeding of two different strains of rat

A McNeilly, R Williamson, D Balfour, C Sutherland & C Stewart


University of Dundee, Dundee, UK.


The incidence of type 2 diabetes (T2DM) has doubled over the past decade. Obesity induced insulin resistance is associated with T2DM and the metabolic syndrome (including hypertension, and dyslipidemia). Diets high in saturated fat are largely to blame for the current obesity epidemic. High-fat feeding of animals increases circulating corticosterone levels, in addition to changes in glucose homeostasis. The relationship between insulin sensitivity and abnormal hypothalamic–pituitary–adrenal (HPA) activity remains unclear.

We compared the effect of a high lard content diet on insulin sensitivity and adrenal/thymus weight in two strains of rat. Male Wistar (W) and Lister Hooded (LH) rats (125–150 g) were randomly assigned to receive either standard laboratory chow (SC; 11% kcal crude oil; n=8 W; n=4 LH) or a high-fat diet (HF; 45% kcal lard; n=16 W; n=8 LH) ad libitum for 10 weeks. Fasting plasma glucose and insulin were measured using Accuread glucose monitor and ELISA respectively. HOMA-S index was calculated as a measure of insulin sensitivity.

HF animals were significantly heavier than SC counterparts (P<0.05). Fasting plasma glucose was greater in HF-W and HF-LH compared to SC animals (P<0.05), however the HOMA-S index revealed a few animals in both HF groups that remained relatively insulin sensitive (25%). Most interestingly, adrenal gland mass was greater in both HF groups compared to SC groups (P<0.05) whilst thymus weight, a measure of circulating corticosterone, was unaltered by diet or strain.

In conclusion, consumption of a high-fat diet induced peripheral insulin resistance and impaired glucose homeostasis. Adrenal hypertrophy in the absence of changes in thymus weight also suggest increased central drive to the HPA axis.

We suggest that the high-fat fed rat provides a model to study the role of adrenal function in the development of peripheral insulin resistance and the associated health problems (e.g. vascular disease, pancreatic failure, and cognitive decline).

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