Dehydroepiandrosterone (DHEA) is reported to exert beneficial effects, such as protection from cardiovascular risk and lowering serum insulin levels. Adipose tissue (AT) is a target for DHEA actions, and the hormone can also affect hepatic fatty acid (FA) metabolism. FAs are involved in the development of insulin resistance; thus, there might be a relationship between DHEA, FA, and insulin. However, few data are available regarding DHEA and FA composition, especially concerning AT. Seventeen-month old female Sprague–Dawley rats (n=11; controls: n=10) were treated with DHEA (0.5% w/w in the diet) for 13 weeks, after which serum, periovarian, mesenteric, s.c., and brown AT were analyzed for FA composition. DHEA treatment resulted in significant changes in FA profiles in serum and adipose depots, like reduced 16:1n-7 (s.c. and brown AT; P<0.01), elevated n-9 monounsaturated FA (serum and s.c. AT; P<0.05), diminished n-6 polyunsaturated FA (PUFA; general; P<0.05) and increased n-3 PUFA (brown AT; P<0.01), along with lower n-6/n-3 ratios (s.c. and brown AT; P<0.05, P<0.01 respectively). DHEA modified estimates of desaturase activities, decreasing stearoyl-CoA-desaturase markers in s.c., and brown AT (P<0.05) and increasing those of delta-6-desaturase in serum and AT (P<0.05). In addition, DHEA-treated rats showed lower serum insulin levels (P<0.05). We have demonstrated for the first time that DHEA induces significant modifications in AT fatty acid composition in vivo, mainly concerning unsaturated FAs, and changes occurred in a tissue-dependent manner. We propose that these changes may be related to the capacity of DHEA to lower serum insulin levels.

Gestational diabetes mellitus (GDM) reduces maternal adiponectin and docosahexaenoic acid (DHA) materno-fetal transfer, which may have negative consequences for the offspring. Our aim was to evaluate the effects of the administration of a novel adiponectin agonist (AdipoRon) to GDM rats on the long-term consequences in glycaemia and fatty acids (FA) profile in the offspring. Pregnant rats were randomized to three groups: GDM rats (GDM, n = 8), GDM rats treated with AdipoRon (GDM + ADI, n = 9), and control rats (n = 10). Diabetes was induced with streptozotocin (50 mg/kg) on day 12 of gestation. GDM+ADI received 50 mg/kg/day AdipoRon from day 14 until delivery. Glycaemia and FA profile were determined in mothers and adult offspring (12 weeks old). AdipoRon tended to reduce fasting glucose in diabetic mothers. Diabetic rats presented the foetus with intrauterine growth restriction and higher adiposity, which tried to be counteracted by AdipoRon. In the adult offspring, both GDM + ADI and control animals showed better glucose recovery after oral glucose overload with respect to GDM. DHA in offspring plasma was significantly reduced in both GDM and GDM + ADI compared to controls (P = 0.043). Nevertheless, n-6/n-3 polyunsaturated FA (PUFA) ratio improved in plasma of GDM + ADI adult offspring (GDM: 14.83 ± 0.85a%; GDM + ADI: 11.49 ± 0.58b%; control: 10.03 ± 1.22b%, P = 0.034). Inflammatory markers and oxidative stress were reduced in the adult offspring of AdipoRon-treated mothers. In conclusion, AdipoRon administration to pregnant diabetic rats improved glycaemia in the mothers and long-term glucose tolerance in the offspring. In addition, it tended to reduce excessive foetal fat accumulation and improved n-6/n-3 PUFA ratio significantly in offspring at the adult state.