Dietary Complex and Slow Digestive Carbohydrates Prevent Fat Deposits During Catch-Up Growth in Rats.

A nutritional growth retardation study, which closely resembles the nutritional observations in children who consumed insufficient total energy to maintain normal growth, was conducted. In this study, a nutritional stress in weanling rats placed on restricted balanced diet for 4 weeks is produced, followed by a food recovery period of 4 weeks using two enriched diets that differ mainly in the slow (SDC) or fast (RDC) digestibility and complexity of their carbohydrates. After re-feeding with the RDC diet, animals showed the negative effects of an early caloric restriction: an increase in adiposity combined with poorer muscle performance, insulin resistance and, metabolic inflexibility. These effects were avoided by the SDC diet, as was evidenced by a lower adiposity associated with a decrease in fatty acid synthase expression in adipose tissue. The improved muscle performance of the SDC group was based on an increase in myocyte enhancer factor 2D (MEF2D) and creatine kinase as markers of muscle differentiation as well as better insulin sensitivity, enhanced glucose uptake, and increased metabolic flexibility. In the liver, the SDC diet promoted glycogen storage and decreased fatty acid synthesis. Therefore, the SDC diet prevents the catch-up fat phenotype through synergistic metabolic adaptations in adipose tissue, muscle, and liver. These coordinated adaptations lead to better muscle performance and a decrease in the fat/lean ratio in animals, which could prevent long-term negative metabolic alterations such as obesity, insulin resistance, dyslipidemia, and liver fat deposits later in life.

Programming Skeletal Muscle Metabolic Flexibility in Offspring of Male Rats in Response to Maternal Consumption of Slow Digesting Carbohydrates during Pregnancy.

Skeletal muscle plays a relevant role in metabolic flexibility and fuel usage and the associated muscle metabolic inflexibility due to high-fat diets contributing to obesity and type 2 diabetes. Previous research from our group indicates that a high-fat and rapid-digesting carbohydrate diet during pregnancy promotes an excessive adipogenesis and also increases the risk of non-alcoholic fatty liver disease in the offspring. This effect can be counteracted by diets containing carbohydrates with similar glycemic load but lower digestion rates. To address the role of the skeletal muscle in these experimental settings, pregnant rats were fed high-fat diets containing carbohydrates with similar glycemic load but different digestion rates, a high fat containing rapid-digesting carbohydrates diet (HF/RD diet) or a high fat containing slow-digesting carbohydrates diet (HF/SD diet). After weaning, male offspring were fed a standard diet for 3 weeks (weaning) or 10 weeks (adolescence) and the impact of the maternal HF/RD and HF/SD diets on the metabolism, signaling pathways and muscle transcriptome was analyzed. The HF/SD offspring displayed better muscle features compared with the HF/RD group, showing a higher muscle mass, myosin content and differentiation markers that translated into a greater grip strength. In the HF/SD group, metabolic changes such as a higher expression of fatty acids (FAT/CD36) and glucose (GLUT4) transporters, an enhanced glycogen content, as well as changes in regulatory enzymes such as muscle pyruvate kinase and pyruvate dehydrogenase kinase 4 were found, supporting an increased muscle metabolic flexibility and improved muscle performance. The analysis of signaling pathways was consistent with a better insulin sensitivity in the muscle of the HF/SD group. Furthermore, increased expression of genes involved in pathways leading to muscle differentiation, muscle mass regulation, extracellular matrix content and insulin sensitivity were detected in the HF/SD group when compared with HF/RD animals. In the HF/SD group, the upregulation of the ElaV1/HuR gene could be one of the main regulators in the positive effects of the diet in early programming on the offspring. The long-lasting programming effects of the HF/SD diet during pregnancy may depend on a coordinated gene regulation, modulation of signaling pathways and metabolic flexibility that lead to an improved muscle functionality. The dietary early programming associated to HF/SD diet has synergic and positive crosstalk effects in several tissues, mainly muscle, liver and adipose tissue, contributing to maintain the whole body homeostasis in the offspring.

A Slow-Digesting Carbohydrate Diet during Rat Pregnancy Protects Offspring from Non-Alcoholic Fatty Liver Disease Risk through the Modulation of the Carbohydrate-Response Element and Sterol Regulatory Element Binding Proteins.

High-fat (HF) and rapid digestive (RD) carbohydrate diets during pregnancy promote excessive adipogenesis in offspring. This effect can be corrected by diets with similar glycemic loads, but low rates of carbohydrate digestion. However, the effects of these diets on metabolic programming in the livers of offspring, 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 different rates of carbohydrate digestion, High Fat-Rapid Digestive (HF-RD) diet or High Fat-Slow Digestive (HF-SD) diet. Offspring 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 offspring 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 offspring, 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.

Feeding a slowly digestible carbohydrate diet during pregnancy of insulin-resistant rats prevents the excess of adipogenesis in their offspring.

An obesogenic environment during pregnancy has been shown to increase the risk of dysregulation on adipogenesis and insulin resistance in the offspring. Being essential for the growing fetus, glucose supply is guaranteed by a number of modifications in the mother's metabolism, and thus, glucose control during pregnancy especially among obese or diabetic women is paramount to prevent adverse consequences in their children. Besides the election of low-glycemic-index carbohydrates, the rate of carbohydrate digestion could be relevant to keep a good glucose control. In the present study, we compared the effects of two high-fat diets with similar glycemic load but different rates of carbohydrate digestion given to pregnant insulin-resistant rats. After birth, all animals were fed a standard diet until age 14 weeks. We analyzed offspring body composition, plasma and adipocyte lipidomics, lipid metabolism in adipose tissue and insulin sensitivity. Those animals whose mothers were fed the rapid-digesting carbohydrate diet exhibited an excessive adipogenesis. Thus, these animals showed a marked lipidemia, increased lipid synthesis in the adipose tissue and reduced glucose transporter amount in the adipose. On the contrary, those animals whose mothers were fed the slow-digesting carbohydrate diet showed a profile in the measured parameters closer to that of the offspring of healthy mothers. These results support the hypothesis that not only glycemic index but the rate of carbohydrate digestion during gestation may be critical to regulate the programming of adipogenesis in the offspring.