Metabolic diseases as obesity and diabetes lead to an increase in cardiovascular risk, morbidity and mortality. Zinc is an essential micronutrient for carbohydrates and lipids metabolism. In previous studies we have demonstrated that zinc deficiency induces cardiovascular and renal alterations associated with an increase in blood pressure. The aim of this work was to evaluate in adult male rats if prenatal and postnatal zinc restriction aggravates the metabolic effects of a high-fat diet (HF) during post-weaning growth. Methods: Female Wistar rats received control (C, 30ppm) or low-zinc diet (L, 8ppm) during pregnancy and lactation. At weaning (day 21) C pups were fed C (Cc) or C-HF diet (CcHF). L offspring received L (Ll) or L-HF diet (LlHF). 60% of total calories of HF hypercaloric diets correspond to fat. Oral glucose tolerance test (OGTT) was performed at day 74. On day 81 rats were sacrificed to evaluate retroperitoneal adipose tissue (RPAT) weight, morphology and oxidative stress. Results: No differences were observed in daily calorie intake. HF diet induced an increase in RPAT weight in Ll (Cc: 1.9 0.3; CcHF: 2.3 0.2; Ll: 1.5 0.2; LlHF: 2.9 0.2† g/100g body weight). In OGTT, HF rats showed an increase in AUC (area under the curve - Cc: 27.8 0.5; CcHF: 30.8 0.9*; Ll: 27.8 0.8; LlHF: 35 1†‡ x1000 min.mg/dl) and in glycemia at 180 min (Cc: 132 5; CcHF: 150 4*; Ll: 149 4*; LlHF: 165 7 mg/dl). Zinc restriction and/or HF diet induce RPAT adipocyte hypertrophy (cell area - Cc: 5.4 0.4; CcHF: 10.7 0.6*; Ll: 8.6 0.4*; LlHF: 11.6 0.5 x1000 m2) and a reduced adipocyte density (cell density - Cc: 24 1; CcHF: 11.2 0.4*; Ll: 13.6 0.4*; LlHF: 11.9 0.4† adipocytes/field). Dietary injuries also affected RPAT oxidative stress by increasing lipid peroxidation (TBARS - Cc: 0.20 0.03; CcHF: 0.30 0.04; Ll: 0.43 0.07*; LlHF: 0.38 0.08 pmol/mg prot) or by reducing superoxide dismutase activity (SOD - Cc: 2.0 0.3; CcHF: 1.1 0.1*; Ll: 2.1 0.2; LlHF: 1.3 0.2† USOD/mg prot). However, no differences were observed in catalase (CAT) activity. Statistics: two-way ANOVA followed by Bonferroni's post-test; *p<0.05 vs Cc, †p<0.05 vs Ll, ‡p<0.05 vs CcHF; n=6/group. Discussion: Zinc restriction
induced RPAT adipocyte hypertrophy accompanied by an increase in lipid peroxidation. HF diet administration resulted in an increase in adipocyte size and a reduced cell density in RPAT of CcHF and LlHF. In addition, HF rats showed a reduced SOD activity that would affect RPAT redox state. Morphological and oxidative stress alterations observed in RPAT would affect carbohydrates metabolism. In this regard, both HF and L diets contributed to a glucose intolerance state, considering the higher glycaemia at 180min of Ll and the increase in AUC in CcHF and LlHF. Moreover, HF only increased RPAT weight in zinc-deficient rats. Zinc restriction and HF diet induce changes in RPAT that would lead to a reduced glucose tolerance, contributing to metabolic diseases development.