ABSTRACT
Hyperglycemia significantly contributes to the development and progression of metabolic diseases. Managing postprandial blood glucose fluctuations is of particular importance for patients with hyperglycemia, but safe and effective means of reducing blood glucose levels are still lacking. Five diets with varying macronutrient ratios and omega-3 fatty acid amounts were tested for their blood glucose-lowering effects in male C57BL/6J mice. The diets with potent blood glucose-lowering effects were further investigated for their underlying mechanisms and their beneficial effects on hyperglycemia models. Mice given the low-carbohydrate, high-protein, and high-omega-3 (LCHP+3) diet exhibited a rapid reduction of the blood glucose levels that remained consistently low, regardless of feeding. These effects were associated with reduced amino acid gluconeogenesis, due to the inhibition of hepatic alanine transaminase (ALT). Furthermore, the LCHP+3 intervention was effective in reducing the blood glucose levels in several disease conditions, including type 1 diabetes mellitus, hormone-induced hyperglycemia, and diet-induced metabolic syndrome. Our findings identify the LCHP+3 diet as a potent blood glucose-lowering diet that suppresses postprandial blood glucose fluctuations through the inhibition of gluconeogenesis and may have great clinical utility for the management of metabolic diseases with hyperglycemia.
Subject(s)
Diabetes Mellitus, Experimental/diet therapy , Diet, Carbohydrate-Restricted , Diet, High-Protein , Fatty Acids, Omega-3/administration & dosage , Gluconeogenesis/drug effects , Hyperglycemia/diet therapy , Metabolic Syndrome/diet therapy , Alanine/metabolism , Alanine Transaminase/metabolism , Animals , Blood Glucose/metabolism , Carbon Isotopes , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/metabolism , Diet, Western/adverse effects , Disease Models, Animal , Hyperglycemia/chemically induced , Hyperglycemia/metabolism , Liver/drug effects , Liver/metabolism , Male , Metabolic Syndrome/etiology , Metabolic Syndrome/metabolism , Mice , Mice, Inbred C57BL , Postprandial Period , Prednisolone/analogs & derivatives , StreptozocinABSTRACT
BACKGROUND: Exposure to fine particulate matter, such as through air pollution, has been linked to the increased incidence of chronic diseases. However, few measures have been taken to reduce the health risks associated with fine particle exposure. The identification of safe and effective methods to protect against fine particle exposure-related damage is urgently needed. METHODS: We used synthetic, non-toxic, fluorescent fine particles to investigate the physical distribution of inhaled fine particles and their effects on pulmonary and systemic inflammation in mice. Tissue levels of omega-3 fatty acids were elevated via dietary supplementation or the fat-1 transgenic mouse model. Markers of pulmonary and systemic inflammation were assessed. RESULTS: We discovered that fine particulate matter not only accumulates in the lungs but can also penetrate the pulmonary barrier and travel into other organs, including the brain, liver, spleen, kidney, and testis. These particles induced both pulmonary and systemic inflammation and increased oxidative stress. We also show that elevating tissue levels of omega-3 fatty acids was effective in reducing fine particle-induced inflammation, whether as a preventive method (prior to exposure) or as an intervention (after exposure). CONCLUSIONS: These results advance our understanding of how fine particles contribute to disease development and suggest that increasing tissue omega-3 levels may be a promising nutritional means for reducing the risk of diseases induced by particle exposure. GENERAL SIGNIFICANCE: Our findings demonstrate that elevating tissue omega-3 levels can prevent and treat fine particle-induced health problems and thereby present an immediate, practical solution for reducing the disease burden of air pollution.
Subject(s)
Fatty Acids, Omega-3/pharmacology , Inflammation/chemically induced , Inflammation/drug therapy , Lung/drug effects , Protective Agents/pharmacology , Air Pollutants/adverse effects , Air Pollution/adverse effects , Animals , Dietary Supplements , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Oxidative Stress/drug effects , Particle SizeABSTRACT
Transgenic mice (named "Omega mice") were engineered to carry both optimized fat-1 and fat-2 genes from the roundworm Caenorhabditis elegans and are capable of producing essential omega-6 and omega-3 fatty acids from saturated fats or carbohydrates. When maintained on a high-saturated fat diet lacking essential fatty acids or a high-carbohydrate, no-fat diet, the Omega mice exhibit high tissue levels of both omega-6 and omega-3 fatty acids, with a ratio of â¼1â¶1. This study thus presents an innovative technology for the production of both omega-6 and omega-3 essential fatty acids, as well as a new animal model for understanding the true impact of fat on human health.
