Medium-chain triglycerides impair lipid metabolism and induce hepatic steatosis in very long-chain acyl-CoA dehydrogenase (VLCAD)-deficient mice.
Study Goal
The researchers aimed to investigate the effects of long-term MCT supplementation on hepatic lipid metabolism in a murine model of VLCADD, comparing it to short-term MCT-bolus administration.
Results Summary
The study found that a long-term MCT diet induced severe hepatic steatosis, elevated serum free fatty acids, and impaired hepatic lipid mobilization in VLCAD-KO mice, while short-term MCT-bolus appeared safer. MCT also upregulated hepatic lipogenic genes, suggesting potential risks with prolonged use.
Population
VLCAD-knockout (KO) mice and wild-type (WT) mice.
Effective Dosage
Not specified (MCT diet and MCT-bolus, exact amounts not detailed).
Duration
5 weeks for both MCT and LCT diets.
Interactions
None mentioned.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
MCT-bolus prior to exercise | neutral | - | - | - | Beneficial effects have been reported | #1 |
LCT-diet over 5weeks | increase | blood cholesterol concentrations | VLCAD-knock-out (KO) mice | significantly higher | accumulated significantly higher | #2 |
MCT diet over 5 weeks | increase | hepatic steatosis | VLCAD-knock-out (KO) mice | severe | induced severe | #3 |
MCT diet over 5 weeks | increase | serum free fatty acids | VLCAD-knock-out (KO) mice | significantly higher | significantly higher | #4 |
MCT diet over 5 weeks | decrease | hepatic lipid mobilization | VLCAD-knock-out (KO) mice | - | impaired | #5 |
MCT diet over 5 weeks | increase | Expression at mRNA level of hepatic lipogenic genes | VLCAD-knock-out (KO) mice | - | up-regulated | #6 |
long-term MCT diet | increase | lipogenesis | VLCAD-knock-out (KO) mice | - | stimulates | #7 |
long-term MCT diet | decrease | hepatic lipid metabolism | VLCAD-knock-out (KO) mice | - | impairs | #8 |
MCT in situations of increased energy demand | neutral | - | - | - | appears to be a safer treatment alternative | #9 |
A medium-chain-triglyceride (MCT)-based diet is mainstay of treatment in very-long-chain acyl-CoA dehydrogenase deficiency (VLCADD), a long-chain fatty acid beta-oxidation defect. Beneficial effects have been reported with an MCT-bolus prior to exercise. Little is known about the impact of a long-term MCT diet on hepatic lipid metabolism. Here we investigate the effects of MCT-supplementation on liver and blood lipids in the murine model of VLCADD. Wild-type (WT) and VLCAD-knock-out (KO) mice were fed (1) a long-chain triglyceride (LCT)-diet over 5weeks, (2) an MCT diet over 5 weeks and (3) an LCT diet plus MCT-bolus. Blood and liver lipid content were determined. Expression of genes regulating lipogenesis was analyzed by RT-PCR. Under the LCT diet, VLCAD-KO mice accumulated significantly higher blood cholesterol concentrations compared to WT mice. The MCT-diet induced severe hepatic steatosis, significantly higher serum free fatty acids and impaired hepatic lipid mobilization in VLCAD-KO mice. Expression at mRNA level of hepatic lipogenic genes was up-regulated. The long-term MCT diet stimulates lipogenesis and impairs hepatic lipid metabolism in VLCAD-KO mice. These results suggest a critical reconsideration of a long-term MCT-modified diet in human VLCADD. In contrast, MCT in situations of increased energy demand appears to be a safer treatment alternative.