P4 Prediabetes induces changes in the brown adipose tissue

Abstract

Introduction: Prediabetes induced by a fructose rich diet (FRD) administration to normal rats for 21 days, promotes a state of insulin resistance (IR), hyperinsulinemia, hypertriglyceridemia, increased oxidative stress and inflammatory response.

Aim: to verify possible changes induced in brown adipose tissue (BAT) in the prediabetes state.

Materials and methods: normal 60-day-old male Sprague Dowley rats were fed with a standard commercial diet (C) or the same diet plus 10% fructose in drinking water (FRD) for 21 days. At the end of the treatment, after sacrificed, plasma levels of glucose (G), triglycerides (TG), total cholesterol, HDL-c were measured, and IR index was calculated by TG/HDL cholesterol ratio. BAT was removed, tissue weight/animal weight ratio and fatty acids composition (FA) were analized. Adipocyte total RNA was isolated and gene expression of insulin cascade indicators, inflammation response, and apoptosis markers were determined by qPCR.

Results: (* p˂ 0.05 vs. C). No changes were observed in G or HDL-c levels, but TG, total cholesterol and TG/HDL ratio increased significantly in FRD group compared to C (174.97 ± 7.7 * vs. 63.93 ± 22.3mg/dl; 120.5 ± 12.5 * vs. 72 ± 6 mg/dl and 4.67 ± 0.5 * vs. 1.45 ± 0.5 respectively). Tissue weight/animal weight ratio significantly increased in the FRD group (86%), where the saturated FA content (43.42 ± 3.1 * vs. 34.86 ± 0.8) and the saturated FA/unsaturated FA ratio also increased significantly. Likewise, mRNA
levels of insulin cascade (PI3K: 1.46 ± 0.003 * vs. 1 ± 0.01); inflammation (TNF-α: 1.98 ± 1.5. 10-6 * vs. 1 ± 0.03); and apoptosis (Bad: 1.30 ± 0.02 * vs. 1 ± 0.03) markers were also significantly increased in FRD group.

Conclusions: Although BAT´s primary function is calorigenic, in the prediabetes state, its mass, saturated FAs content, gene expression of insulin cascade mediators, apoptosis and inflammation markers increase. Probably, during this state, BAT would change its function, contributing to a general metabolic dysfunction.