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Weight Control: Beyond Calories In and Out

Research is proving that weight control may require more than simply balancing the amount of energy consumed with the amount of energy expended in physical activity. This article looks at some of the findings from recent research.

Viruses

• Injections of several viruses into the central nervous system lead to obesity in mice.
• Antibodies to adenovirus Ad-36 (most commonly known to cause respiratory infections, gastritis, cystitis, and eye infections) are found in larger amounts in obese humans. When primates are injected with these antibodies, they develop modest obesity and have lower levels of circulating cholesterol concentration.
• Stem cells exposed to Ad-36 are converted into fat cells.
• Ad-36 seems to increase the number and size of fat cells.
• In one study, 30% of obese individuals were infected with adenovirus-36, while only 5%-10% of normal weight people were.

Drugs

• Many hormonal and psychoactive agents will lead to weight gain, but usually will not cause substantial obesity.
• High-dose corticosteroids, some psychoactive drugs (including neuroleptics) and antidepressants, and medications for seizure disorder (particularly valproate) may lead to substantial obesity.

Toxins

• In some animals, exposure to monosodium glutamate (MSG) during the neonatal period leads to obesity later in life, possibly by damaging the metabolic sensors that regulate food intake.
• In one study, MSG-treated hamsters had significantly increased body mass, total and individual white adipose tissue pad masses, and serum leptin concentrations.
• The metabolic rate may decrease from exposure to organochlorine molecules. It is feared that prolonged exposure to these chemicals in our modern environment may have affected our metabolic pathways and energy metabolism.
• Organochlorine is stored in adipose tissue. When weight is lost, plasma organochlorine concentrations increase, as do the concentrations in remaining adipose tissue. This increase appears to decrease triiodothyronine (T3) concentrations, and to decrease the resting metabolic rate and fat oxidation. This could encourage weight regain or prevent further weight loss.

Hormones

• Leptin is produced in adipose tissue and secreted in the blood relative to the amount of fat.
• Leptin-deficient people are massively obese.
• Exogenous administration caused a decrease in body weight, body fat, and food intake, while increasing energy expenditure in rodents. It is unclear if this same effect would occur when administering leptin to obese people.
• Leptin administration also attenuates the decrease in thyroid hormone concentration caused by weight loss.
• More leptin is produced by subcutaneous adipose tissue than visceral adipose tissue.
• Females produce about twice as much leptin as males.
• Leptin concentration increases with enlarged adipocytes.
• Circulating leptin rises by 40% after acute overfeeding and more than threefold after chronic overfeeding.
• Obese people have higher concentrations of circulating leptin, but exogenous administration leads to inconsistent results.
• Obesity is possibly related to a leptin resistance, rather than a deficiency.
• Leptin concentrations are correlated to peripheral and subcutaneous fat stores.
• Fasting and energy restriction lead to a decrease in leptin concentration.
• High-carbohydrate, low-fat diets produce increases in leptin concentration, when compared to high-fat, low-carbohydrate diets.
• High-fat feedings produce leptin resistance in rats.
• If leptin levels are decreased, fewer calories are burned; so, individuals gain weight even if they are not eating more.
• Leptin resistance develops with aging, obesity, Cushing's syndrome, and acquired lipodystrophy, a condition associated with protease inhibitor therapy of AIDS.

Melanocortin-4-receptor:

• Polymorphisms in the amino acid sequencing of melanocortin-4-receptors lead to massive obesity.
• Binge eating disorder is very closely linked to mutations of the receptor.

Cortisol:

• Production of cortisol from inactive cortisone in fat cells determines the amount of visceral adipose tissue. Changes to the enzyme 11-B-hydroxysteroid dehydrogenase type 1 (the enzyme responsible for changing cortisol to cortisone) may help to explain the tendency for women to gain weight during menopause.
• No evidence shows that the amount of cortisol released by a healthy individual under temporary stress is enough to lead to weight gain. However, chronic stress that lasts for several months or years may lead to weight gain. Questions exist about whether cortisol levels actually increase prior to weight gain, or whether weight gain leads to an increased production and release of the hormone.

Ghrelin

• Ghrelin stimulates food intake and growth hormone secretion.
• Concentrations are generally lower in the obese, with the exception of people with Prader-Willi syndrome (possibly the reason or part of the reason for hyperphagia).
• Administration of ghrelin in rats leads to an increase in food intake and body weight.
• People with anorexia nervosa have high levels of circulating ghrelin, leading researchers to believe that people with anorexia nervosa may have ghrelin resistance.
• Ghrelin causes an increased respiratory quotient in rodents, without concurrent increases in energy expenditure. Therefore, it is believed that ghrelin increases carbohydrate concentration, while decreasing fat oxidation.
• Carbohydrate suppresses ghrelin concentrations, and it is believed that a high-carbohydrate, low-fat diet may mitigate the resultant increase in ghrelin when a person is on a reduced-calorie, weight-loss diet.
• Ghrelin concentrations are increased preprandially and when in negative energy balance, and are decreased postprandially and when in positive energy balance.
• Fiber may decrease ghrelin concentration.

PYY3-36 (hormone peptide YY):

• When peripherally administered, PYY leads to a decrease in appetite.
• Some studies show that obese people have less circulating PYY, but these findings are controversial, and other studies have found no such relationship.
• Higher concentrations are observed postprandially.
• Patients with anorexia nervosa have had higher levels than the rest of the population, and these levels do not seem to change during and after treatment.

CCK (cholecystokinine):

• CCK is a satiating hormone.
• Administration decreases individual meal size, but not overall intake, and does not produce sustained weight loss, probably because of a compensatory increase in number of meals consumed.
• The decreased satiety response in rats administered CCK during fasting is weakened by leptin administration.
• Fat and protein increase postprandial CCK concentrations more than carbohydrates.
• When rats are fed a high-fat, low-carbohydrate diet, they display reduced satiety in response to CCK administration and do not reduce their food intake as much as rats consuming a high-carbohydrate, low-fat diet.

Sleep and hormones:

• Leptin levels are decreased and ghrelin levels are increased in people who sleep less than 7-9 hours a night.
• A study at the University of Chicago demonstrated that when men were only permitted to sleep for 4 hours for 2 consecutive nights, their leptin was 18% lower and their ghrelin 28% higher than when they were allowed to sleep for 10 hours. These participants also reported an increase in appetite for salty, sweet, and starchy foods.

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Review Date 8/09
G-1105