Continuous intake of Trehalose induces white adipose tissue Browning and Enhances energy metabolism

Abstract

Background Trehalose is well known as a functional disaccharide with anti-metabolic activities such as suppression of adipocyte hypertrophy in mice and alleviation of impaired glucose tolerance in humans. Recently, a new type of adipocyte beige cells, involved in so-called white adipocyte tissue (WAT) browning, has received much attention as a target for adaptive thermogenesis. To clarify the relationship between adipocyte hypertrophy suppression and beige cells involved in thermogenesis, we examined the effect of trehalose on the changes in beige adipocytes in mice under normal dietary conditions. Methods Mice fed a normal diet were administered water containing 0.3% (W/V) trehalose for 16 weeks, 0.3% (W/V) maltose, or water without saccharide (controls). Body temperature and non-fasting blood glucose levels were measured every 3 weeks. After 16 weeks of these treatments, mesenteric and inguinal adipose tissues were collected for measuring adipocyte size, counting the number of UCP1 positive cells by image analysis, and preparing mRNA to analyze beige adipocyte-related gene expression. Results Mice administered a continuous intake of trehalose exhibited a thermogenic ability as represented by an increase in rectal temperature, which was maintained at a relatively high level from 3 to 9 weeks and was significantly higher at 15 weeks in comparison with that of the maltose group. In addition to the reduced hypertrophy of mesenteric and inguinal adipose tissues, the trehalose group showed a significant increase in the rates of beige adipocytes in each WAT in comparison with those of the maltose and the water groups. Interestingly, a negative correlation was found between the mean cell sizes of adipocytes and the rates of beige adipocytes in the WAT. Furthermore, real-time PCR showed that the expression of Cidea and Ucp1 mRNAs, which are markers for beige adipocytes in the inguinal adipose tissue, increased in the trehalose group. Conclusions Continuous administration of trehalose to mice fed a normal diet induced WAT browning accompanied by suppression of white adipocyte hypertrophy, elevated body temperature and decreased blood glucose levels, which resulted in enhancement of energy metabolism. Therefore, we propose trehalose as a new type of thermogenic dietary component to prevent obesity by promoting WAT browning.

Daily consumption of one teaspoon of trehalose can help maintain glucose homeostasis: a double-blind, randomized controlled trial conducted in healthy volunteers

“…A single dose of trehalose does not stimulate a rapid increase in blood glucose or the excessive secretion of insulin or gastric inhibitory polypeptide, which promote fat accumulation, in healthy humans [21]. Furthermore, we have recently shown that daily administration of trehalose to healthy mice consuming a standard diet induces an increase in the number of beige adipocytes, accompanied by a reduction in adipocyte hypertrophy, higher body temperature, and lower blood glucose [22]. Therefore, regular consumption of trehalose may reduce adipocyte size and induce qualitative changes in adipocytes, which may result in lower postprandial blood glucose concentration.…”

Variability in the metabolism of saccharides in bladder and colon cancer cell lines

“…In the case of trehalose, HT29 colon cancer cells were an exception in that growth was stimulated by trehalose. Trehalose is not thought to be a major nutrient for mammalian cells but it has been reported to have a variety of effects including actions on subcellular trafficking and increasing energy metabolism and autophagy [14,15]. The action on HT29 colon cancer cells may merit further investigation.…”

Trehalose itself plays a critical role on lipid metabolism: Trehalose increases jejunum cytoplasmic lipid droplets which negatively correlated with mesenteric adipocyte size in both HFD-fed trehalase KO and WT mice

“…We have continuously been reported that trehalose suppresses adipocyte hypertrophy and mitigates insulin resistance [1][2][3]. We also demonstrated that trehalose induces white adipose tissue (WAT) browning with suppressing white adipocyte hypertrophy, increasing body temperature, and reducing blood glucose levels even under normal dietary conditions [4]. Trehalose has an inhibitory effect on adipocyte hypertrophy that is not seen for other saccharides.…”