Modulation of Adipose Lipoprotein Lipase by Thyroid Hormone and Diabetes: The Significance of the Low T3 State

Abstract

The present study was performed to assess the potential relationship between the low T3 syndrome and hypothyroidism. Comparative studies were performed on the relative effects of diabetes and insulin on heparinreleasable adipose lipoprotein lipase (LPL) in the intact and hypothyroid rat. Hypothyroidism for 10 days (Tx) significantly increased adipose LPL activity (5.8 ± 0.2 μeq/g/h) compared with the activity (3.6 ± 0.4 μeq/g/h) in the normal group. Diabetes for 72 h (streptozocin, STZ, 10 mg/100 g body wt, i.p.) significantly reduced (P < 0.005) adipose LPL activity in the Tx model. However, despite the suppressant effect of diabetes (43 ± 11%), the enzyme activity remained equivalent to the normal group. Insulin stimulated adipose LPL in the Tx-diabetic group. The enzyme demonstrated a synergistic response to insulin and hypothyroidism. Subsequent studies were performed in the intact diabetic rat, a low T3 state. Adipose LPL activity was reduced to a similar degree by diabetes (79 ± 2%) irrespective of the serum T3 concentration. Furthermore, the magnitude of the adipose LPL stimulation by insulin was not modulated by the endogenous serum T3. However, co-treatment of the diabetic group with T3 and insulin blunted the adipose LPL response to insulin. These various modulations in adipose LPL activity were associated with significant but opposite changes in serum triglyceride levels in both the hypothyroid and intact rat. These studies demonstrate that hypothyroidism counteracts the suppressant effect of diabetes on heparin-releasable rat adipose LPL activity and magnifies the enzyme response to insulin. The synergistic effect of hypothyroidism and insulin on adipose LPL activity suggests that the enzyme responds through different mechanisms. In contrast, the low T3 state associated with diabetes did not influence the adipose LPL response to diabetes or insulin therapy. Thus, the low T3 state in the rat does not reflect hypothyroidism. The low T3 state may, however, have a permissive role as it facilitated the adipose LPL response to insulin in the diabetic rats. Therefore, T3 therapy is contraindicated under these condition.