Obesity: Deadly Killer Of MillionsObesity in the U.S. is a deadly epidemic. It causes about 300,000 deaths each year. About 100 million adults are obese, so are twelve million children. If you have high blood sugar there are many ways to control it. From 1971 to 2000 obesity rates increased from 14 to 31 percent.A grossly overweight person has a body mass index (BMI), a comparison of weight and height, of over 30 kilograms/meters squared. People with a BMI greater than 40 are morbidly overweight. The condition increases the risk of type 2 diabetes, hypertension, heart disease and cancer. Link here to see how the symptoms of this deadly disease can be managed. In 2010, no state had a prevalence of obesity less than 20%. In twelve states, 30 percent or more of the population was obese. Obesity in the United States cost $150 billion per year in direct medical outlays, which is about nine percent of all medical spending. The average adult American consumes about 657,000 calories a year, or 1,800 a day. The body, through a balancing mechanism called homeostasis, knows when it should eat and and when to stop eating. Increased calorie intake, lack of physical activity and environmental pollutants that disrupt fat metabolism help explain the condition, but its regulation is in the genes. What are the obesity genetics? Leptin is a hormone made in fat cells that travels through the blood to the brain into the hypothalamus. The protein, encoded by the ObLep gene, acts via its receptor LepRb as a regulator that balances the intake of energy with its expenditure. When leptin is at a low level, it signals to the body that it’s time to eat. When it’s at a high level it does the opposite... People with a mutation of the lepin gene, or its cell receptors, have a permanent low level of the hormone and insatiable hunger. Since they always have a need to eat, and do, they become morbidly obese. Numerous FDA clinical trials have shown that treatment with the hormone reduces body weight, but only temporarily, it’s soon regained. This happens because most humans who are obese are leptin resistant. Leptin resistance happens when the body fails to transport the hormone past the blood brain barrier into the hypothalamus where it can act on leptin receptors. There is a class of FDA approved drugs that increase leptin sensitivity by ten-fold and causes weight loss: TUDCA, or tauroursodeoxycholic acid, and 4-PBA (4-phenyl butyric acid) are used and treat urea cycle disorders and cystic fibrosis.  White and brown are the two types of fat or adipose tissue. Brown fat, or the good fat, burns white fat as fuel and gives off heat. The good fat is full of blood and iron rich mitochondria, which gives it a dark color. Both types store facts as trigylcerides. The protein PRDM16 (proline rich domain-containing protein 16) is a dominant regulator of brown fat. It's able to switch between an association with processor proteins to induce brown fat expression. Modulation of the protein can regulate fat cell expression to favor brown fat. Brown fat is good at converting calories into energy, but the capacity of brown fat to burn calories is inhibited by obesity. Good fat is more closely related to muscle than white fat, and becomes activated when cold. It’s critical in keeping infants, who do not shiver, warm. About two ounces of brown fat account for nearly one-fifth of a person’s energy expenditure. Activating brown fat would cause the loss of about 10 pounds a year without diet or exercise. Two molecular pathways have been identified that block necdin, a promoter protein that decreases the growth of brown fat.
The cannabinoid receptor type 1 (CB1) is located in the brain. It is activated by cannabinoid neurotransmitters, including anadamide and cannabis. Inhibition of the receptor reduces body weight and blood glucose by increasing calorie burning in brown adipose tissue.There are several CB1 selective inhibitors. TM38837 as a peripherally restricted CB1 receptor antagonist for indications such as obesity and metabolic disorders without inducing psychiatric side effects. 7TM Pharma successfully conducted clinical phase I trial of its second generation CB1 receptor antagonist. Estrogen regulates energy expenditure, appetite and body weight in women. Insufficient estrogen receptors in the brain can lead to obesity. Two hypothalamic centers in the brain keeps female body weight in check by regulating hunger and calorie expenditure. Similar results were not seen in men. PPAR gamma is the master controller of fat cell formation. They are cell surface nuclear receptors that receive hormone and chemical signals. PPAR gamma control metabolism of food: carbohydrates, fat and protein, and the genes that regulate energy metabolism. Ligands, agonists or antagonists, are chemical modulators that activate, up-regulate or deactivate, down-regulate PPARs affecting fat metabolism and controlling obesity.
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