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

Abstract

Background: Trehalose is a functional disaccharide that has anti-metabolic activities such as suppression of adipocyte hypertrophy in mice and alleviation of impaired glucose tolerance in humans. Trehalase hydrolyzes trehalose in the small intestine into two glucose molecules. In this study, we investigated whether trehalose can suppress adipocyte hypertrophy in mice in the presence or absence of trehalase. Methods: Trehalase knockout (KO) mice and wild-type (WT) mice were fed a high fat diet (HFD) and administered water with 0.3% (w/v) or without trehalose for 8 weeks. At the end of the experimental period, mesenteric adipose tissues and the small intestine were collected and the adipocyte size and proportion of cytoplasmic lipid droplets (CLDs, %) in jejunum epithelium were measured by image analysis. Results: Trehalose treatment was associated with suppressed adipocyte hypertrophy in both trehalase KO and WT mice. The rate of CLDs in the jejunal epithelium was increased in both trehalase KO and WT mice given water containing trehalose relative to untreated control mice. There was a negative correlation between jejunal epithelial lipid droplet volume and mesenteric adipocyte size. Chylomicron-TG tended to be decreased in both trehalose-treated trehalase KO and WT mice. Addition of trehalose to differentiated Caco-2 cells in vitro increased intracytoplasmic lipid droplets and decreased secretion of the chylomicron marker ApoB-48. Moreover, the jejunal epithelium containing lipid droplets falled into the intestinal lumen, and triglyceride (TG) levels in feces tended to be higher in the KO/HFD/Tre group than in the KO/HFD/Water group. Since then, the accumulation of CLDs has been reported to suppress CM secretion, and along with our results, the effect of trehalose to increase jejunum CLDs may induce suppression of adipocyte hypertrophy.

RETRACTED: Trehalose improves palmitic acid‐induced apoptosis of osteoblasts by regulating SIRT3‐medicated autophagy via the AMPK/mTOR/ULK1 pathway

“…12 Trehalose participated in the process of lipid metabolism that could suppress adipocyte hypertrophy. 13 The negative effect on adipogenesis might be a positive effect on osteogenesis. Additionally, a previous study also demonstrated that Trehalose could improve bone mass in cirrhosis rats by increasing the formation of autophagosome, which indicated autophagy might play an important role in the treatment of osteoporosis by Trehalose.…”

Lipids and Trehalose Actively Cooperate in Heat Stress Management of Schizosaccharomyces pombe

“…Its "career" started as a cell stabilizer in the dry state [12], and emerged so rapidly that a myth grew up about trehalose as a universal protectant and chemical chaperone [13]. Indeed, this disaccharide is important for widespread industrial and medical applications [13][14][15][16][17]. In yeast, trehalose is synthesized in a two-step process in which glucose-6-phosphate and UDP-glucose are converted to trehalose-6-phosphate by trehalose-6-phosphate synthase (Tps), then trehalose-6-phosphate is converted to trehalose by trehalose-6-phosphate phosphatase.…”

Targeting hepatocyte carbohydrate transport to mimic fasting and calorie restriction

“…Trehalose and LT reduced fructose‐induced hepatic steatosis and induced hepatocyte fasting response signals, PGC1α, TFEB, and FGF21. Extrahepatic cardiometabolic effects of these compounds are broad, including peripheral insulin sensitization [118], activating peripheral thermogenesis, reduced adipocyte hypertrophy [119,120], in addition to reduced atherosclerotic plaque lesion area [27,121] and pathological cardiac remodeling in response to injury [122,123], that mimicked ketogenic dietary effects on heart failure [37]. Treating liver‐specific GLUT8‐deficient mice with oral trehalose did not increase the efficacy of trehalose on diet‐induced hepatic steatosis, which implies some mechanistic overlap between GLUT8 deletion and trehalose action [9].…”