Beneficial effects of thyroid hormone on adipose inflammation and insulin sensitivity of obese Wistar rats

Abstract

Thyroid hormones play an important role in glucose metabolism and there is evidence of increased prevalence of thyroid dysfunction in obese and diabetic patients. This study aimed at evaluating the thyroid function and the effects of the triiodothyronine (T3) treatment on glycemia control, insulin sensitivity and subclinical inflammation in cafeteria-diet-induced obesity in rats. Obesity was induced in male Wistar rats by offering a cafeteria diet and a subset of the obese rats was treated with T3 (1.5 μg per 100 g of body weight) for a 28-day period. The pituitary-thyroid axis was evaluated by molecular and biochemical parameters. Cytokine content was measured in the serum as well as in the mesenteric and epididymal white adipose tissue. Obese rats exhibited impairment of glycemia control, increased content of inflammatory cytokines in mesenteric white adipose tissue, decreased serum thyrotropin (TSH) concentration and increased sodium/iodide symporter (NIS) and TSH receptor (TSHR) protein content in thyroid gland. T3 treatment improved insulin sensitivity, glucose tolerance, and reduced inflammatory cytokine content in mesenteric white adipose tissue. In the thyroid gland NIS, TSHR, and thyroperoxidase (TPO) content were reduced while thyroglobulin (TG) content was increased by T3. The thyrotrophic response to negative feedback exerted by T3 was preserved in obese rats. The present data reinforce the beneficial effects of T3 treatment of obese rats on the improvement of insulin sensitivity and on the negative modulation of inflammatory cytokine expression in adipose tissue. Moreover, we have evidenced that the pituitary-thyroid axis is affected in obese rats, as illustrated by the impaired TSH secretion.

Keywords: Adipose tissue; cytokines; insulin sensitivity; obesity; triiodothyronine.

Figure 1

Body weight evolution during experimental protocol (A), insulin tolerance test – ITT (B); rate constant for ITT ‐ kITT (C); glucose tolerance test ‐ GTT (D); area under curve (AUC) for GTT (E) of C (n = 10), O (n = 12) and OT3 (n = 12) rats. Data were analyzed by analysis of variance (one way ANOVA) and Student–Newman–Keuls posttest and expressed as mean ± SEM normalized by total protein content. *P < 0.05 versus C, ** P < 0.01 versus C, & P < 0.05 versus O.

Figure 2

Analysis of TNF‐α (A), IFN‐у (B), CCL‐2 (C), Leptin (D), IL‐1β (E),IL‐1α (F), IL‐6 (G) and IL‐10 (H) concentration in mWAT of C (n = 10), O (n = 12) and OT3 (n = 12) rats. Data were analyzed by analysis of variance (one way ANOVA) and Student–Newman–Keuls posttest and expressed as mean SEM normalized by total protein content. *P < 0.05 versus C, & P < 0.05 versus O.

Figure 3

Analysis of TNF‐α (A), IFN‐у (B), CCL‐2 (C), Leptin (D), IL‐1β (E), IL‐1α (F), IL‐6 (G) and IL‐10 (H) concentration in eWAT of C (n = 10), O (n = 12) and OT3 (n = 12) rats. Data were analyzed by analysis of variance (one way ANOVA) and Student–Newman–Keuls posttest and expressed as mean SEM normalized by total protein content. & P < 0.05 versus O.

Figure 4

Analysis of serum TNF‐α (A), IFN‐у (B), CCL‐2 (C), Leptin (D), IL‐1β (E),IL‐1α (F), IL‐6 (G) and IL‐10 (H) concentration of C (n = 10), O (n = 12) and OT3 (n = 12) rats. Data were analyzed by analysis of variance (one way ANOVA) and Student–Newman–Keuls posttest and expressed as mean SEM. *P < 0.05 versus C.

Figure 5

Tshb mRNA expression (A) and TSHB protein content (B) on pituitary; TSHR (C), NIS (D), TG (E) and TPO (F) protein content on thyroid of C (n = 10), O (n = 10) and OT3 (n = 10) rats. Above each graph a typical autoradiogram is shown. Data were analyzed by analysis of variance (one way ANOVA) and Student–Newman–Keuls posttest and expressed as mean ± SEM normalized by Rpl19 mRNA (A), GAPDH content (B), and by Ponceau‐stained membrane – supplementary material (C, D, E, and F). *P < 0.05 versus C, & P < 0.05 versus O.