TOXINS AND NEUROTOXICITY PATHOGENESIS OF OBESITY-EXPOSED

UNDERLYING MECHANISMS

The influence of toxins on metabolism occurs through 5 key

• Mechanisms
• Hormonal regulation,
• Neuro-regulatory mechanisms,
• Immune-regulatory mechanisms,
• Mitochondrial function, and
• Oxidative stress.

Toxins can alter the hormonal regulation of weight, a process that involves insulin, leptin, thyroid, cortisol, adiponectin, resistin, sex hormones, and gut hormones, including ghrelin, peptide (PYY), and cholecystokinin (CCK).   Toxins alter thyroid hormone metabolism and receptor function leading to lowered metabolic rate. Important Neuro-regulatory mechanisms affected by toxins include hypothalamic satiety modulation through effects on peripheral and central inhibitors and stimulators of appetite, including leptin, cortisol, melanocyte stimulating hormone (MSH), and neuropeptide (NPY). Stress induced autonomic dysfunction it also alters appetite and weight-control mechanisms.   Toxins can influence weight through toxin mediated increases in inflammatory cytokines (TNF-α, IL-6) on the peroxisome proliferator activated receptor (PPAR) family of nuclear receptors promoting insulin resistance, and on themelanocortin receptor (MCR) system altering central appetite regulation.   Counter regulatory signals triggered by inflammation such as suppressors of cytokine signaling (SOCS) induce leptin resistance. Toxins alter mitochondrial energetics by damaging enzymes involved in fatty acid oxidation and thermogenesis. Oxidative stress influences weight via NFκ B-mediated mechanisms of gene transcription that control insulin resistance and inflammation. Other mechanisms may include direct effects of toxins on hepatic control of lipid and glucose metabolism, and on inflammatory cytokines  

WEIGHT REGULATION AND TOXINS -WHERE DO TOXINS COME FROM?

Exposure to toxins comes from two main sources: the environment (external toxins) and the gut (breakdown products of our metabolism, or internal toxins). Both can overload endogenous detoxification mechanisms.    External Toxins The Dangers from without the external toxins include chemical toxins and heavy metals. The heavy metals that cause the most ill health are lead, mercury, cadmium, arsenic, nickel, and aluminum.   Chemical toxins include volatile organic compounds (VOCs), solvents (cleaning materials, formaldehyde, toluene, and benzene), medications, alcohol, pesticides, herbicides, and food additives.   Infections (hepatitis C virus) and mold toxins (sick building syndrome) are other common sources of toxins. Our modern refined diet can be considered toxic because it places an extra burden on detoxification systems through excessive consumption of sugar, high fructose corn syrup (the two most important causes of elevated liver function tests),trans fatty acids, alcohol, caffeine, aspartame, foods made with genetically modified organisms (GMOs), and the various plastics, pathogens, hormones, and antibiotics found in our food supply. Internal Toxins: Danger from Within Internal toxins include microbial compounds (from bacteria, yeast, or other organisms), and the breakdown products of normal protein metabolism.   Bacteria and yeast in the gut produce waste products, metabolic by-products and cellular debris that can interfere with many body functions and lead to increased inflammation and oxidative stress. These include endotoxins, toxic amines, toxic derivatives of bile, and various carcinogenic substances such as putrescence and cadaverine. Lastly, by-products of normal protein metabolism, including urea and ammonia, require detoxification

WEIGHT REGULATION AND TOXINS-Detoxification Enzyme Polymorphisms and Obesity

The effect of toxins on an individual is determined, in part, by the polymorphisms of phase I and phase II detoxification enzymes. Highly prevalent single nucleotide polymorphisms (SNPs) of glutathione transferase enzymes predispose to increased toxic loads.   Detoxification of heavy metals is an important task for the body. It depends on specific proteins and enzymes that bind the metals and transport them out of the cells. In one recent study, mice bred without the protein (metallothionein) that is necessary for heavy metal detoxification gained more weight over their lifetime than mice that could eliminate the metals. They were more sensitive to the effects of toxic metals and oxidative stress.   Toxins Impair Central Appetite Regulation Toxins have many effects. Besides directly lowering thyroid hormone levels, metabolic rate, and fat burning (fatty acid oxidation), they can damage the mechanisms by which hormonal and Neuro-regulatory signals control our appetite and behavior. These signals are finely choreographed and sensitive to environmental inputs.   To briefly review, the hypothalamic appetite-control system is centered in the acute nucleus. It receives peripheral feedback from leptin, insulin, PYY, and adiponectin. Central inhibition of food intake is regulated by pro-opiomelanocortin (POMC) and cocaine-and amphetamine regulated transcript (CART). Central stimulation of intake is modulated by Neuropeptide Y and agouti related peptide (AgRP).   The melanocortin system and its receptors, MC3R and MC4R, play a crucial role in appetite control. Specifically, MSH binds to MCR, suppresses appetite, stimulates the thyroid axis, and increases energy expenditure, brown fat temperature, and sympathetic activity. It is inhibited by TNF. Other downstream control sites also exist in the related areas of the brain. Reward centers also play a role and are targets for new drug research including the end cannabinoid and serotonin receptors. Leptin resistance is found in obesity.   Leptin’s inhibitory effect on appetite is impaired by toxins, leading to leptin resistance and increased hunger. Hyperleptinemia increases mitochondrial reactive oxygen species monocyte chemo attractant protein-1 (ROS MCP-1). Leptin induces inflammation in a feed-forward cycle. Toxins may inhibit satiety effects of leptin, leading to increasing hyperleptinemia. Researchers treated rats with a neurotoxin that damaged another.

WEIGHT REGULATION AND TOXINS-What Are the Benefits of Detoxing Your Body?

Detoxification is the process of removing toxins from the body. The process to detoxify your body involves many different elements such as herbal detoxification regimens, change of diet and vitamin supplements. It is one of the best ways to rid your body of toxins, which can slow it down and make it unhealthy. The process of detoxification requires some discipline. Physical Benefits The most noticeable benefits from detoxification are the physical ones. Since the toxins store up in major organs, detoxification will help these areas the most. The organs which are affected, such as the liver and stomach, will begin to work more effectively. After the detox is completed, you may feel “lighter” and have more energy. Also, since a detox is used to clear away free radicals, your body’s immune system will be stronger and you will have a lower risk of getting cancer. Finally, a detoxification regimen will clear your blood, helping it circulate better.   Mental Benefits Toxins and free radicals that accumulate in the body can also affect brain functions. Before a detox, you may have trouble sleeping, chronic fatigue, and trouble with your concentration. Once you work through this process, many of these issues will gradually disappear. You will be able to sleep better and concentrate more. Lifestyle Changes A benefit which most people don’t think of can be the change to your lifestyle. As you progress through the body detox, you will begin to feel better physically and mentally. This feeling can be addictive and lead to changing your lifestyle to cut out bad elements which give your body those toxins. Quitting smoking, eating better, and getting more exercise are all actions which help protect the body. After a detox is a perfect time to begin these actions.

TOXINS AND NEUROTOXICITY PATHOGENESIS OF OBESITY-EXPOSED