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Rat Transthyretin: Effects of Acute Short-Term Food Deprivation and Refeeding on Serum and Cerebrospinal Fluid Concentration and on Hepatic mRNA Level

Unité de Recherches sur la Nutrition et l'Alimentation, U.1 INSERM, Hôpital Bichat, 75018 Paris, France

To gain some insight into the nutritional factors that affect the blood level of transthyretin (TTR) and its metabolism, we have investigated the response of rat TTR to 1, 2 and 3 d of fasting and to 24 h of fasting followed by refeeding. The observed changes were compared to the level of TTR in cerebrospinal fluid (CSF) and to the amount of circulating thyroid hormones. Dot hybridization of a hepatic mRNA-cDNA probe specific for TTR was used to measure the relative level of TTR mRNA. Serum TTR decreased significantly after fasting and the decrease was proportional to the duration of the treatment. When rats were fasted for 24 h and then refed, serum TTR levels remained low after 2 d of refeeding. The dot hybridization results suggested that reduced liver synthesis was not the only mechanism that could explain this long-lasting effect of fasting. The TTR level in CSF was not influenced by fasting. In addition to the high sensitivity of serum TTR to food deprivation, the study also showed two distinct influences of fasting on the thyroid hormones: a primary effect that probably results in an inhibition of the conversion of thyroxine (T₄) to triiodothyronine (T₃) and a decreased T₄-bound fraction, probably as a result of decreased serum level of TTR.

KEY WORDS: • fasting • rat transthyretin • cerebrospinal fluid • transthyretin cDNA • hepatic transthyretin mRNA • thyroid hormones

¹ To whom correspondence should be addressed.

Manuscript received 2 February 1987. Revision accepted 27 October 1987.