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Abstract: Objective: GLUT4 protein, encoded by the Slc2a4 gene, plays a key role in muscle glucose uptake, and its expression decreases in muscles under insulin resistance. Slc2a4/GLUT4 decreases with fasting and rapidly increases with refeeding and the same occurs to plasma glucose, amino acids, insulin and T3. Thus, they might be potential regulators of the Slc2a4 gene, which makes them promising targets for strategies to improve GLUT4 expression. Herein, we investigate the role of metabolic–hormonal parameters triggered by refeeding upon the Slc2a4 expression. Materials/Methods: Plasma glucose/insulin/T3, and gastrocnemius Slc2a4 mRNA contents were measured in rats studied at the end of 48-h fasting, and subsequently at: i) 2–4h after spontaneous refeeding; ii) 2–4h after T3 injection, without refeeding; and iii) 0.5–2h after intravenous infusion of insulin, insulin+glucose and insulin+amino acids, without refeeding. Results: Refeeding increased plasma glucose/insulin/T3 and muscle Slc2a4 mRNA, reverting insulin resistance. Post-fasting infusions surprisingly induced a further Slc2a4 mRNA decrease (~20%, P <0.05 vs. fasting), but T3 injection induced a ~2-fold increase in Slc2a4 mRNA, 2–4h later (P <0.001). Moreover, T3 increased glycemia and insulinemia to the 2h-refed rats levels, suggesting that T3 elevation is a key factor to the mechanisms of metabolic balance during refeeding. Conclusions: Refeeding induces a rapid increase in muscle Slc2a4 expression, not associated with increased plasma glucose, insulin or amino acids, but highly correlated to increased plasma T3 concentration. This result points out T3 hormone as a powerful Slc2a4 enhancer, an effect that may be acutely explored in situations of insulin resistance. [Copyright &y& Elsevier]

Acutely ill patients typically present with low circulating T3 and increased reverse T3. When illness is severe and prolonged, also pulsatile TSH secretion and circulating T4 levels are low. This constellation of changes within the thyroid axis is referred to as the low T3 syndrome or non-thyroidal illness syndrome (NTI), and comprises both peripheral and central alterations in the thyroid axis. Acute alterations are dominated by changes in thyroid hormone binding, in thyroid hormone uptake by the cell and in the activity of the type-1 and type-3 deiodinase enzymes. Prolonged critical illness is associated with a neuroendocrine dysfunction characterized by suppressed hypothalamic thyrotropin-releasing hormone (TRH) expression, resulting in reduced stimulation of the thyrotropes whereby thyroidal hormone release is impaired. During prolonged critical illness, several tissue responses could be interpreted as compensatory to low thyroid hormone availability, such as increased expression of monocarboxylate transporters, upregulation of type 2 deiodinase activity and increased sensitivity at the receptor level. Whether the low T3 syndrome should be treated and which compound should be used remains to be further studied. [Copyright &y& Elsevier]

Summary: Obesity has a prevalence of 15–30% among European and American populations. It is an incurable chronic disease associated with considerable mortality and co-morbidity. The co-morbidity risk can be reduced substantially by a moderate weight loss of 5–15%. Notably, additional weight gain exacerbates the morbidity of any concurrent disease. Obesity is also recognized as the basis for metabolic syndrome. Recent research has shown that adipocytes secrete various hormones and cytokines that contribute to obesity. Leptin is an adipostatic hormone that acts on receptors in the hypothalamus to suppress food intake and increase energy consumption. Reduced sensitivity to this molecule can trigger the onset of obesity. Neuropeptides such as leptin also affect salivary secretion. Various neuropeptides have been identified in saliva; the associated receptors are located in the salivary glands or in the nerves innervating the salivary glands. Obesity is associated with hyposalivation and thereby related to several aspects of oral health, such as caries and periodontitis. Hyposalivation is a severe morbidity that can lead to a precipitous decline in oral hygiene, which further leads to multifocal dental caries and periodontitis, or even cardiac disorders. In this article, we review the relationship between salivary secretion and neuropeptides known to play a role in obesity. [Copyright &y& Elsevier]