Overnutrition determines LPS regulation of mycotoxin induced neurotoxicity in neurodegenerative diseases

Chronic neurodegenerative diseases are now associated with obesity and diabetes and linked to the developing and developed world. Interests in healthy diets have escalated that may prevent neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease. The global metabolic syndrome involves lipoprotein abnormalities and insulin resistance and is the major disorder for induction of neurological disease. The effects of bacterial lipopolysaccharides (LPS) on dyslipidemia and NAFLD indicate that the clearance and metabolism of fungal mycotoxins are linked to hypercholesterolemia and amyloid beta oligomers. LPS and mycotoxins are associated with membrane lipid disturbances with effects on cholesterol interacting proteins, lipoprotein metabolism, and membrane apo E/amyloid beta interactions relevant to hypercholesterolemia with close connections to neurological diseases. The influence of diet on mycotoxin metabolism has accelerated with the close association between mycotoxin contamination from agricultural products such as apple juice, grains, alcohol, and coffee. Cholesterol efflux in lipoproteins and membrane cholesterol are determined by LPS with involvement of mycotoxin on amyloid beta metabolism. Nutritional interventions such as diets low in fat/carbohydrate/cholesterol have become of interest with relevance to low absorption of lipophilic LPS and mycotoxin into lipoproteins with rapid metabolism of mycotoxin to the liver with the prevention of neurodegeneration

Type 3 diabetes with links to NAFLD and Other Chronic Diseases in the Western World

In the year 2015 it is now estimated that 30% of the Western World will now progress to non alcoholic fatty liver disease (NAFLD) and by the year 2050 if NAFLD remains untreated in the Western world the prevalence of the disease may rise to 40% of the global population. Type 3 diabetes and circadian rhythm disturbances may be involved in the induction of NAFLD that may promote insulin resistance and various chronic diseases such as cardiovascular disease, pancreatic disease, kidney disease and neurodegenerative disease. Multiple risk factors that induce Type 3 diabetes and NAFLD include stress, magnesium deficiency, bacterial lipopolysaccharide contamination, drug induced toxicity, xenobiotic levels, unhealthy diet/lifestyle factors and defective thermoregulation. Early diagnosis of Type 3 diabetes by multiple assessment techniques such as proteomics, genomics and lipidomics may allow reversal or stabilization of NAFLD that may progress slowly from simple non-alcoholic steatosis to non-alcoholic steatohepatitis and to hepatic fibrosis/cirrhosis of liver and hepatoma. Analysis of plasma constituents such as heat shock proteins (60,70, 90), amyloid beta, adiponectin, fibroblast growth factor 21, ceramide, sphingosine-1-phosphate, vasoactive intestinal peptide, thrombospondin 1, acute phase reactants may indicate progression of Type 3 diabetes and NAFLD and these results may not be consistent with normal plasma glucose and cholesterol levels. Early nutritional interventions with temperature regulation are required to reverse premature brain disease in diabetes (Type 3/Type2) that is connected to the rapid metabolism of heat shock proteins and amyloid beta oligomers that determine the severity of insulin resistance and NAFLD in individuals in the Western World

Induction of NAFLD With Increased Risk Of Obesity And Chronic Diseases In Developed Countries

The susceptibility of individuals to obesity has been reported in many developed countries with predisposition of humans to obesity associated with high calorie diets and unhealthy lifestyles. Obesity may closely be involved in cell suicide in various organ diseases with the importance of accelerated aging that requires early intervention with drug therapy to prevent diseases such as non alcoholic fatty liver disease (NAFLD) that has increased in children and reached to approx. 40% of the global population. Obesity is induced by various diets and lifestyle factors such as stress, anxiety and depression which are important to consider with the global increase in obesity and are possibly linked to the rise in individuals with brain disorders that involve neurodegeneration. Xenobiotics such as the endocrine disruptor chemicals that have increased in the environment in various developed countries lead to various chronic endocrine diseases as populations divert towards unhealthy diets and lifestyles with induction of NAFLD and obesity. The amount and nature of food intake that improves and increases liver lipid and xenobiotic metabolism in obese individuals have become important to decrease the risk for increased adiposity in man. High fibre or protein diets that contain leucine may improve liver glucose, lipid and xenobiotic metabolism and require further investigation with xenobiotics such as endocrine disruptors involved in appetite dysregulation and metabolic disorders in developed countries. The use of anti-obese drugs that reduce food intake and improve hypercholesterolemia and cardiovascular disease has been assessed in obesity with drug therapy closely involved either in the prevention or induction of NAFLD and obesity in man

Increased Risk for Obesity and Diabetes with Neurodegeneration in Developing Countries

The incidence of global obesity and Type 2 diabetes has increased and is predicted to rise to 30% of the global population. Diet and lifestyle factors are incapable to resolve the increased incidence for obesity and diabetes in various populations of the world. Developing countries have come to the forefront because of the higher diabetic epidemic. The urbanization may possibly provide an explanation for the global diabetic epidemic. In Western countries the metabolic syndrome and non alcoholic fatty liver disease (NAFLD) have reached 30 % of the population and now at present NAFLD afflicts 20% of developing populations. Western diets and sedentary lifestyles cause metabolic disorders in developing countries which may increase neurodegenerative diseases by the disrupted metabolism of xenobiotics in urban populations. In developing countries access to high calorie diets in urban areas down regulate liver nuclear receptors that are responsible for glucose, lipid and toxicological sensing and interrupt the metabolism of xenobiotics that become toxic to various tissues such as the pancreas, heart, kidney, brain and liver. Xenobiotics in urban areas induce epigenetic changes that involve chromatin remodelling by alterations in transcriptional regulators with modification of histones. Dysfunction of nuclear receptors such as the calorie sensitive sirtuin 1 (Sirt 1) gene involves abnormal nutrient metabolism with insulin resistance, NAFLD, energy balance and circadian rhythm disorders. In obesity and diabetes insulin resistance has been connected to poor xenobiotic metabolism with the toxic affects of increased xenobiotic transport to the brain associated with neurodegeneration. Dietary interventions to increase xenobiotic metabolism are likely to reduce oxidative stress and neuroendocrine disease in developing countries. Prevention programs are an important goal of international health organizations and in developing countries the plans to adapt a healthy diet, active lifestyle and reduced exposure to xenobiotics are important to manage the global epidemic for obesity and diabetes

Food quality induces a miscible disease with relevance to Alzheimer’ s disease and neurological diseases

Food and nutrition guidelines for the handling and processing of fresh fruit, bread, and vegetables are essential and fresh produce may require cold preservation procedures to prevent minimal bacterial and fungi contamination of food. Bacterial lipopolysaccharides (LPS) corrupt lipoprotein and amyloid beta (Aβ) metabolism in diabetes, Alzheimer’s disease (AD) and various neurological diseases. In the developing world the increased plasma LPS levels induce non-alcoholic fatty liver diseases and interfere with albumin and Aβ interactions with spontaneous Aβ oligomer formation in the cerebrospinal fluid and brain that leads to neuronapoptosis by inactivation of Starling’s equation that is responsible for the maintenance of hydrostatic and oncotic pressure with relevance to fluid balance. In the developing world increased levels of LPS, mycotoxin and xenobiotics lead to irreversible neurological diseases by inhibition of Starling’s equation for maintenance of oncotic/osmotic pressure that lead to neuron senescence or apoptosis. In the developed world nutrigenomic diets are required that prevent Sirtuin 1 gene repression and maintain neuron survival that links the brain and peripheral hepatic monomer Aβ metabolism. The maintenance of blood-cerebrospinal fluid capillary transport of albumin and monomer Aβ is relevant to stabilization of neurons not only in Alzheimer’s disease but also in Type 3 diabetes and various neurological diseases. Healthy diets reverse the inhibition of brain to peripheral Aβ transport that is sensitive to Starling’s equation for regulation of central nervous system hydrostatic and oncotic pressure with the prevention of diabetes, various neurological diseases and Alzheimer’s disease

Appetite control with relevance to mitochondrial biogenesis and activation of post-prandial lipid metabolism in obesity linked diabetes

In various communities in the developing and developed world the understanding of the ingestion of a healthy diet [1] and hepatic fat metabolism has become of critical importance to the treatment of obesity linked Type 2 diabetes that is now linked to various organ diseases [2]. In the developing world transition to healthy diets has become urgent to prevent insulin resistance [3,4] and the obesity pandemic [5-8]. The liver is the major organ for the metabolism of dietary fat and after consumption of a meal in healthy individuals the fat is rapidly metabolized by the liver. In obesity linked Type 2 diabetes the post-prandial metabolism of a fat meal by the liver is defective with fat transport to the adipocyte relevant to adipocyte and brain appetite centre dysfunction [9-11] (Figure 1). In obese and diabetic mice post-prandial lipid metabolism has been shown to be defective with defects in the appetite centre associated with hyperglycemia and hyperphagia. Activation of hepatic fat metabolism with restricted food intake in these rodent studies may be relevant to adipocyte lipid metabolism and adipocyte signals that relate to appetite control [12] are vital to the treatment of obesity linked diabetes [13]

Drug therapy for obesity with anti-aging genes modification

Nutritional regulation and drug therapy has been the focus of the current obesity epidemic in various countries in the world. Epigenetics is the major mechanism for the development of insulin resistance and obesity with unhealthy diets, oxidative stress and environmental factors relevant to alterations in gene expression with effects on mitochondrial biogenesis, adipose tissue lipid metabolism and energy expenditure. Anti-aging genes are involved in the regulation of adipogenesis with increased sensitivity to anti-aging gene dysfunction associated with adipocyte-neuron interactions compared to other cells. Unhealthy diets downregulate adipocyte anti-aging genes associated with the development of Non Alcoholic Fatty Liver Disease (NAFLD) with relevance to regulation of drug metabolism and delayed pharmacokinetics in the body. Evaluation by different methods and techniques to quantify and characterize adiposity has been undertaken to obtain a better understanding of adipocyte metabolism in obesity but adipocyte analysis is now required to determine adipose tissue anti-aging gene expression. Effective drug treatment programs cannot be determined in individuals with obesity with defective adipocyte tissue gene expression. New drug development needs to be carefully interpreted in relation to nutritional intake with drug safety concerns/adverse effects relevant to adipogenesis and NAFLD in obesity