Triiodothyronine differentially regulates key metabolic factors in lean and obese cats

The effect of a 2-week administration of 75microg triiodothyronine (T3) on substrate oxidation, heat production, non-esterified fatty acids, and leptin was evaluated in eight lean (three females and five males) and eight obese (five females and three males) age-matched adult neutered cats. In addition, using real-time RT-PCR, expression of muscle and adipose tissue uncoupling proteins (UCP2 and UCP3), deiodinase 1 and 2 (D1; D2), and peroxisome proliferator-activated receptor (PPAR) alpha and gamma and peroxisome-proliferator-activator receptor-gamma co-activator 1alpha (PGC1) was examined. Compared to lean cats, obese cats had increased NEFA, leptin, UCP2, and D1mRNA in muscle and UCP3mRNA levels in fat, but lower heat production, and fat PPARs and PGC1. T3 administration increased thermogenesis and NEFA in lean and obese cats, and adipose tissue PPARgamma in lean cats. It also increased muscle D1 in lean and D2 in obese cats. The increase in muscle D2 was interpreted to be reflective of the reduced serum total T4 concentration following T3 suppression of the pituitary. No effect was seen on leptin, or UCP2 and 3. This shows that T3 regulates thermogenesis but not through changes in uncoupling protein expression. It also indicates that PPARs have an important role in the pathogenesis of obesity in cats.