Obesity increases free thyroxine proportionally to nonesterified fatty acid concentrations in adult neutered female cats

Abstract

The obese cat is a model for the study of the progression toward type 2 diabetes. In this study, the impact of obesity on the hypothalamic-pituitary-thyroid axis was examined in 21 domestic shorthair cats before and after the development of obesity, which significantly increased body mass index (BMI), % body fat (BF), and girth (P!0 . 0001 for all). Serum total thyroxine (TT 4 ), tri-iodothyronine, free T 4 (FT 4 ) by direct dialysis, nonesterified fatty acids (NEFA), and leptin were measured, and FT 4 fraction (FFT 4 ) was calculated. Serum thyrotropin (TSH) concentrations were measured in nine animals by validating a heterologous canine TSH assay with recombinant feline TSH as a standard. FT 4 , FFT 4 , NEFAs, and leptin were significantly higher in obese cats. FT 4 had the strongest positive correlation with obesity indices BF, BMI, girth, NEFA, and leptin. Fatty acids oleate and palmitate were shown to inhibit T 4 binding to pooled cat serum in vitro, suggesting the possibility that this mechanism was also relevant in vivo. Serum TT 4 and TSH did not rise significantly. The implications for thyroid hormone (TH) action are not yet clear, but fatty acids have been proposed to inhibit the cellular uptake of TH and/or pituitary TH receptor binding, leading to TH resistance. Increased leptin may also alter sensitivity to negative feedback of TH. In conclusion, feline obesity is associated with a significant increase in FT 4 within the normal range; future investigation into the cellular thyroid status will be necessary to establish cause and effect in this obesity model.

Metabolic Effects of Obesity and Its Interaction with Endocrine Diseases

“…No increase in thyroid-stimulating hormone was found with weight gain in cats, although free T4 was increased with obesity, likely because of increased NEFA concentrations. 70 In obese dogs, total T4 and triiodothyronine were both slightly increased, but there was no change in thyroid-stimulating hormone or free T4. 71 Insulinlike growth factor-1 concentrations have also been reported to increase with development of obesity in dogs.…”

Effect of macronutrients, age, and obesity on 6- and 24-h postprandial glucose metabolism in cats

“…The higher fasting NEFA concentrations in obese cats were likely caused by lower lipoprotein lipase activity (24) and may have led to the trend toward an increase in FT4 concentration because we have previously shown that the in vitro addition of palmitate and oleate to cat plasma, within a physiological concentration range, leads to a significant increase of the free T4 fraction (17).…”

Relationship of adiponectin and its multimers to metabolic indices in cats during weight change

“…At time 0, a bolus of 50% dextrose (0.5 g/kg; Hospira, Lake Forest, IL, USA) was injected intravenously. Blood samples were collected at 2, 3,4,5,6,8,10,12,14,16,19,22,24,25,27,30,40, 50, 60, 70, 80, 90, 100, 120, 140, 160, and 180 min. At 20 min after glucose injection, regular human insulin (Humulin R; Lilly, Indianapolis, IN, USA; 0.05 U/kg) was injected via the central catheter.…”

“…As fat concentrations rise, leptin is released from adipocytes and targets areas of the brain such as the hypothalamus to reduce food intake and increase energy expenditure [2]. Leptin correlates positively with body fat mass in cats [3][4][5][6][7] and appears to correlate positively with insulin resistance, independent of adiposity [8].…”