A molecular mechanism for diacylglycerol-mediated promotion of negative caloric balance

Hidekatsu Yanai^1,2, Yoshiharu Tomono³, Kumie Ito^1,2, Yuji Hirowatari⁴, Hiroshi Yoshida^1,5, Norio Tada^1,2

¹Department of Internal Medicine, ²Institute of Clinical Medicine and Research, ³Department of Nutrition, ⁵Department of Laboratory Medicine, Jikei University School of Medicine, chiba, Japan; ⁴Bioscience Division, Tosoh Corporation, Kanagawa, Japan

Aims: A substitution of diacylglycerol (DAG) oil for triacylglycerol (TAG) oil in diet has been reported to reduce body fat and body weight, possibly by increasing postprandial energy expenditure (EE). We have previously studied plasma serotonin, which increases EE and exists in the small intestine, in individuals who ingested TAG and DAG oil, and found that DAG ingestion elevates plasma serotonin levels by about 50% compared with TAG ingestion. We studied the molecular mechanisms for DAG-mediated increase in serotonin and EE.

Methods: We studied effects of 1-monoacylglycerol and 2-monoacylglycerol, distinct digestive products of DAG and TAG, respectively, on serotonin release from the Caco-2 cells (the human intestinal cell line, n = 8). Further, we studied effects of 1- and 2-monoacylglycerol, and serotonin on expression of mRNA associated with β-oxidation, FA metabolism, and thermogenesis, in the Caco-2 cells (n = 5).

Results: 1-monoacylglycerol (100 µM 1-monooleyl glycerol [1-MOG]) significantly increased serotonin release from the Caco-2 cells compared with 2-monoacylglycerol (100 µM 2-MOG) by 36.6%. Expression of mRNA of acyl-CoA oxidase (ACO), fatty acid translocase (FAT), and uncoupling protein-2 (UCP-2) were significantly higher in 100 µM 1-MOG-treated Caco-2 cells than 100 µM 2-MOG-treated cells by 12.8%, 23.7%, and 35.1%, respectively. Further, expression of mRNA of ACO, medium-chain acyl-CoA dehydrogenase, FAT, and UCP-2 were significantly elevated in serotonin (400 nM)-treated Caco-2 cells compared with cells incubated without serotonin by 28.7%, 30.1%, and 39.2%, respectively.

Conclusions: Our study demonstrated that 1-monoacylglycerol, a digestive product of DAG, increases serotonin release from the Caco-2 cells, and enhances expression of genes associated with β-oxidation, FA metabolism, and thermogenesis, and that serotonin increases expression of these genes, proposing a novel molecular mechanism for DAG-mediated promotion of negative caloric balance.

Keywords: diacylglycerol, energy expenditure, intestine, serotonin, triacylglycerol