| First Author | Ghosh S | Year | 2016 |
| Journal | Nutr Metab (Lond) | Volume | 13 |
| Pages | 17 | PubMed ID | 26933443 |
| Mgi Jnum | J:356011 | Mgi Id | MGI:7762103 |
| Doi | 10.1186/s12986-016-0075-0 | Citation | Ghosh S, et al. (2016) Short chain acyl-CoA dehydrogenase deficiency and short-term high-fat diet perturb mitochondrial energy metabolism and transcriptional control of lipid-handling in liver. Nutr Metab (Lond) 13:17 |
| abstractText | BACKGROUND: The liver is an important site of fat oxidation, which participates in the metabolic regulation of food intake. We showed previously that mice with genetically inactivated Acads, encoding short-chain acyl-CoA dehydrogenase (SCAD), shift food consumption away from fat and toward carbohydrate when tested in a macronutrient choice paradigm. This phenotypic eating behavior suggests a link between fat oxidation and nutrient choice which may involve an energy sensing mechanism. To identify hepatic processes that could trigger energy-related signals, we have now performed transcriptional, metabolite and physiological analyses in Acads-/- mice following short-term (2 days) exposure to either high- or low-fat diet. METHODS AND RESULTS: Metabolite analysis revealed 25 acylcarnitine species that were altered by diet and/or genotype. Compared to wild-type mice, phosphorylated AMP-activated protein kinase was 40 % higher in Acads-/- mice after short-term high-fat diet, indicating a low ATP/AMP ratio. Metabolite analyses in isolated liver mitochondria from Acads-/- mice during ADP-linked respiration on butyrate demonstrated a reduced oxygen consumption rate (OCR) compared to wild-type, an effect that was not observed with succinate or palmitoylcarnitine substrates. Liver transcriptomic responses in Acads-/- mice fed high- vs. lowfat diet revealed increased RXR/PPARA signaling, up-regulation of lipid handling pathways (including beta and omega oxidation), and increased mRNA expression of Nfe2l2 target genes. CONCLUSIONS: Together, these results point to an oxidative shortage in this genetic model and support the hypothesis of a lower hepatic energy state associated with SCAD deficiency and high-fat diet. |
