A Slow-Digesting Carbohydrate Diet during Rat Pregnancy Protects O spring from Non-Alcoholic Fatty Liver Disease Risk through the Modulation of the Carbohydrate-Response Element and Sterol Regulatory Element Binding Proteins Salto González, Rafael Manzano, Manuel Girón González, María Dolores Cano, Ainara Castro, Azucena Dámaso Vílchez, José Cabrera, Elena López-Pedrosa, José María Early programming Hepatic lipogenesis Insulin-resistant pregnancy Metabolic flexibility Non-alcoholic fatty liver disease Slow digesting carbohydrates High-fat (HF) and rapid digestive (RD) carbohydrate diets during pregnancy promote excessive adipogenesis in o spring. This e ect can be corrected by diets with similar glycemic loads, but low rates of carbohydrate digestion. However, the e ects of these diets on metabolic programming in the livers of o spring, and the liver metabolism contributions to adipogenesis, remain to be addressed. In this study, pregnant insulin-resistant rats were fed high-fat diets with similar glycemic loads but di erent rates of carbohydrate digestion, High Fat-Rapid Digestive (HF–RD) diet or High Fat-Slow Digestive (HF–SD) diet. O spring were fed a standard diet for 10 weeks, and the impact of these diets on the metabolic and signaling pathways involved in liver fat synthesis and storage of o spring were analyzed, including liver lipidomics, glycogen and carbohydrate and lipid metabolism key enzymes and signaling pathways. Livers from animals whose mothers were fed an HF–RD diet showed higher saturated triacylglycerol deposits with lower carbon numbers and double bond contents compared with the HF–SD group. Moreover, the HF–RD group exhibited enhanced glucose transporter 2, pyruvate kinase (PK), acetyl coenzyme A carboxylase (ACC) and fatty acid (FA) synthase expression, and a decrease in pyruvate carboxylase (PyC) expression leading to an altered liver lipid profile. These parameters were normalized in the HF–SD group. The changes in lipogenic enzyme expression were parallel to changes in AktPKB phosphorylation status and nuclear expression in carbohydrate-response element and sterol regulatory element binding proteins. In conclusion, an HF–RD diet during pregnancy translates to changes in liver signaling and metabolic pathways in o spring, enhancing liver lipid storage and synthesis, and therefore non-alcoholic fatty liver disease (NAFLD) risk. These changes can be corrected by feeding an HF–SD diet during pregnancy. 2019-05-18T22:31:24Z 2019-05-18T22:31:24Z 2019-04-14 info:eu-repo/semantics/article Salto González, R. [et al.]. A Slow-Digesting Carbohydrate Diet during Rat Pregnancy Protects O spring from Non-Alcoholic Fatty Liver Disease Risk through the Modulation of the Carbohydrate-Response Element and Sterol Regulatory Element Binding Proteins. Nutrients 2019, 11, 844; doi:10.3390/nu11040844. 2072-6643 http://hdl.handle.net/10481/55768 10.3390/nu11040844 eng http://creativecommons.org/licenses/by/3.0/es/ info:eu-repo/semantics/openAccess Atribución 3.0 España MDPI