ABSTRACT
The increasing prevalence of obesity and its effects on our society warrant intensifying basic animal research for understanding why habitual intake of highly palatable foods has increased due to recent global environmental changes. Here, we report that pregnant mice that consume a diet high in omega-6 (n-6) polyunsaturated fatty acids (PUFAs) and low in omega-3 (n-3) PUFAs (an n-6high/n-3low diet), whose n-6/n-3 ratio is approximately 120, induces hedonic consumption in the offspring by upregulating the midbrain dopaminergic system. We found that exposure to the n-6high/n-3low diet specifically increases the consumption of palatable foods via increased mesolimbic dopamine release. In addition, neurodevelopmental analyses revealed that this induced hedonic consumption is programmed during embryogenesis, as dopaminergic neurogenesis is increased during in utero access to the n-6high/n-3low diet. Our findings reveal that maternal consumption of PUFAs can have long-lasting effects on the offspring's pattern for consuming highly palatable foods.
Subject(s)
Diet , Fatty Acids, Omega-3/administration & dosage , Fatty Acids, Omega-6/administration & dosage , Feeding and Eating Disorders/etiology , Maternal Exposure/adverse effects , Prenatal Exposure Delayed Effects , Animals , Biomarkers , Brain/metabolism , Brain/physiopathology , Disease Models, Animal , Disease Susceptibility , Dopamine/biosynthesis , Dopaminergic Neurons/metabolism , Female , Fluorescent Antibody Technique , Hyperphagia , Lipid Metabolism , Mice , Mice, Knockout , Obesity/etiology , Obesity/metabolism , PregnancyABSTRACT
1-Deoxynojirimycin (DNJ) is a potent α-glucosidase inhibitor and thus beneficial for prevention of diabetes. While we have succeeded in obtaining the culture supernatant extract (CSE) rich in DNJ from microorganism source, information regarding its anti-hyperglycemic effect and safety were still limited. Therefore, this study was aimed to evaluate the anti-hyperglycemic effect and safety of microorganism DNJ. Oral sucrose tolerance test was performed, and the result showed that CSE was able to significantly suppress the blood glucose elevation and suggested DNJ as the main active compound. To determine its safety, the absorption and excretion of microorganism DNJ were evaluated using 15N labeling method. Our findings investigated the recovery rate of 15N from DNJ reached 80% up to 48 hours after oral administration, suggesting its rapid excretion, suggesting the safety of DNJ. This study verified the functional properties and safety of DNJ from microorganisms, suggesting its potential use for functional purpose.
Subject(s)
1-Deoxynojirimycin/metabolism , Bacillus amyloliquefaciens/chemistry , Hypoglycemic Agents/metabolism , 1-Deoxynojirimycin/administration & dosage , 1-Deoxynojirimycin/analysis , Animals , Bacillus amyloliquefaciens/metabolism , Blood Glucose/analysis , Chromatography, High Pressure Liquid , Drug Evaluation, Preclinical , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/analysis , Isotope Labeling , Male , Mice , Nitrogen Isotopes/chemistry , Nitrogen Isotopes/metabolism , Rats, Sprague-Dawley , Tandem Mass SpectrometryABSTRACT
Phospholipid peroxidation is considered to be involved in the pathophysiology of various diseases. While dietary antioxidants are believed to help prevent these diseases via inhibition of phospholipid peroxidation, further evaluation is needed to prove this hypothesis. For this, it is crucial to establish an animal model with accelerated phospholipid peroxidation. In this study, we hypothesized that a combination of aging and high-fat diet feeding may accelerate phospholipid peroxidation in vivo. High-fat diets were fed to mature and juvenile Fischer 344 rats for 12 weeks. The mature rats in particular accumulated body fat and liver phosphatidylcholine hydroperoxide (PCOOH). Interestingly, the increase in PCOOH levels was abrogated by the co-administration of antioxidants to mature rats. This may be attributed to factors including the decrease in body fat, functions of vitamin E, and/or the involvement of antioxidant-related genes, each caused by antioxidant administration. These results indicate that the high-fat diet-fed aging animal model may be suitable for investigation of the relationship between phospholipid peroxidation, oxidative stress-related diseases, and dietary antioxidants.
