Obesity and Metabolic Disorders
Obesity, a serious condition which is a precursor to other illnesses, is becoming the norm is most developed and even non-developed countries in the world. While the causes are many, including over eating and lack of exercise, the resulting effect is clear, and is creating an impending health care crisis tsunami. Obesity related disorders such as insulin resistance (type II diabetes), atherosclerosis, arthritis, non-alcoholic fatty liver, cancer and other diseases will become prominent as the population ages. Inflammation plays a central role in the pathogenesis of these diseases.
The visceral adipose tissue in obese individuals is a major source of pro-inflammatory adipokines, and is associated with the development of insulin resistance and a disease state referred to as metabolic syndrome.(1) The pro-inflammatory substances from adipocytes and adipose tissue include hormonal (endocrine) and non-hormonal adipokines. Metabolic syndrome is characterized by obesity (especially high visceral fat), high blood sugar, high blood pressure and other factors. Visceral fat plays a central role in the generation of pro-inflammatory molecules which negatively impact the body. Studies in aging lab animals show that by preventing the accumulation of visceral fat the incidence of insulin resistance and diabetes can be significantly reduced.(2) By its very nature, metabolic syndrome is very detrimental to health, and significantly increases the risk of cardiovascular disease and diabetes.(3)
Adipose Tissue: Endocrine Gland & Adipose Tissue Remodeling
Endocrine Gland: The body fat (adipose tissue) which is present in an overweight or obese person is a major source of hormones (adipokines) including inflammatory adipokines. Acting as an endocrine gland, adipose tissue secretes hormones effecting energy balance, appetite and metabolism. Adipocytes (fat cells) are the exclusive secretors of the hormones adiponectin and leptin in the body. A third adipokine secerted by adipocytes is resistin. In obesity there is a shift of cytokine secretion which creates a pro-inflammatory chronic state in the body. Visceral adipose tissue plays an especially important role as an endocrine gland.
Adipose Tissue Remodeling (Pathological Changes): Another source of inflammation involves the “remodeling” or the pathological alteration of the adipose tissue in obese individuals. Remodeled adipose tissue creates a source of continual cycle of chronic inflammation.(16) Obesity, therefore, is a disease associated with constant inflammation originating in the adipose tissue, and which is toxic to the body. Chronic inflammation increases risk of cardiovascular disease, insulin resistance and type II diabetes.(4)
The Adipose Tissue (Adipocyte) Endocrine Hormones
(1) Adiponectin –An anti-inflammatory adipokine. Serum levels are INVERSELY RELATED to obesity. Therefore, with increased obesity there are lower levels of adiponectin. Adiponectin is a critical hormone for the suppression of metabolic disorders and is correlated with increased insulin sensitivity, anti-inflammatory, and anti-atherosclerosis. Higher levels of adiponectin are associated with better health.
(2) Leptin –Normally, serum leptin levels rise when there is an increase in food intake. Leptin then acts upon receptors in the hypothalamus of the brain, to suppress appetite. Fasting or very low calorie diet decreases levels of leptin, thereby increasing the appetite. Chronically high levels of leptin (due to leptin resistance) are related to obesity, overeating and inflammatory diseases. LEPTIN RESISTANCE IS ASSOCIATED WITH OBESITY, WHERE LEPTIN LEVELS REMAIN CHRONICALLY ELEVATED. With leptin resistance the hypothalamus becomes desensitized to the leptin signal. As a result, the leptin message to decrease appetite, fat stores and burn fat is not received. Instead, appetite is further increased (because of perceived low leptin levels) and the body stores even more of the food intake as fat. Therefore, for an obese individual with leptin resistance, it becomes most difficult to reduce weight.
Leptin Resistance can lead to:
• Ectopic fat storage – Dangerous fat accumulation on internal organs and arteries (visceral fat).
• Sets the stage for chronic low grade inflammation, including increased risk of cardiovascular disease, insulin resistance, diabetes and osteoarthritis.(7)
Leptin Activation of the Sympathetic Nervous System. Leptin also stimulates the sympathetic nervous system, which can have significant health consequences when leptin levels remain high. Unlike the hypothalamus, the sympathetic nervous system DOES NOT become leptin resistant. So, high leptin levels (associated with obesity) can over stimulate of the sympathetic nervous system, and sets the stage for the following serious problems:
• Increased arterial blood pressure.
• Cardiovascular Disease including endothelium dysfunction(5)
• Pro-inflammatory State (IL-6 production)
• Metabolic Syndrome (Type 2 Diabetes)(6)
(3) Resistin – Serum levels of resistin INCREASES with obesity. Classified as a pro-inflammatory adipokine, resistin acts as a source of inflammation, and is believed to be involved in the development of insulin resistance (which is a major factor the development of type II diabetes). Furthermore, resistin also acts to increase the expression of other inflammatory cytokines. (7)
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