Killer Carbs: Scientist Finds Key To Overeating As We Age

ScienceDaily (Aug. 22, 2008) — A Monash University scientist has discovered key appetite control cells in the human brain degenerate over time, causing increased hunger and potentially weight-gain as we grow older. The research by Dr Zane Andrews, a neuroendocrinologist with Monash University's Department of Physiology, has been published in Nature.

Dr Andrews found that appetite-suppressing cells are attacked by free radicals after eating and said the degeneration is more significant following meals rich in carbohydrates and sugars.

"The more carbs and sugars you eat, the more your appetite-control cells are damaged, and potentially you consume more," Dr Andrews said.

Dr Andrews said the attack on appetite suppressing cells creates a cellular imbalance between our need to eat and the message to the brain to stop eating.

"People in the age group of 25 to 50 are most at risk. The neurons that tell people in the crucial age range not to over-eat are being killed-off.

"When the stomach is empty, it triggers the ghrelin hormone that notifies the brain that we are hungry. When we are full, a set of neurons known as POMC's kick in.

"However, free radicals created naturally in the body attack the POMC neurons. This process causes the neurons to degenerate overtime, affecting our judgement as to when our hunger is satisfied," Dr Andrews said.

The free radicals also try to attack the hunger neurons, but these are protected by the uncoupling protein 2 (UCP2).

Dr Andrews said the reduction in the appetite-suppressing cells could be one explanation for the complex condition of adult-onset obesity.

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http://www.sciencedaily.com/releases/2008/08/080821110113.htm

New master switch found in the brain that regulates appetite and reproduction

August 31st, 2008 in Medicine & Health / Research

Body weight and fertility have long known to be related to each other – women who are too thin, for example, can have trouble becoming pregnant. Now, a master switch has been found in the brain of mice that controls both, and researchers at the Salk Institute for Biological Studies say it may work the same way in humans.

Findings from the study, published ahead of print in the Aug. 31 online edition of Nature Medicine, suggest that variations in the gene that produces this master switch, known as TORC1, could contribute a genetic component to obesity and infertility, and might be regulated with a novel drug.

"This gene is crucial to the daisy chain of signals that run between body fat and the brain," says Marc Montminy, Ph.D., a professor in the Clayton Foundation Laboratories for Peptide Biology, who led the study. "It likely plays a pivotal role in how much we, as humans, eat and whether we have offspring."

It is just as important as leptin, the well-known star regulator of appetite, Montminy says, because leptin turns on TORC1, which in turn activates a number of genes known to help control feeding and fertility.

Judith Altarejos Ph.D., first author on this study, had been trying to understand human energy balance, and what can go awry to promote obesity, diabetes and other metabolic syndromes. In this study, she looked at the signals that travel from body fat to the brain, informing the brain of how well fed the body is. The primary hormone that performs that function is leptin, which travels through the bloodstream to the hypothalamus in the brain (the appetite center), keeping the brain aware of the body's nutritional status.

"Leptin tells the brain that times are good, your body is full, and that it is not necessary to eat more at the moment," Montminy says. The hormone also is known to play a role in reproduction - although, until this study, no one understood what is was. (Very thin women often do not have periods.)

"Controlling appetite and reproduction together provides a big evolutionary advantage," Montminy says. "If there is no food, the brain believes the body should not reproduce because without body fat, a baby's growth in the womb could be stunted, and without food to replenish the body's energy reserves, there will be nothing to feed the offspring."

"Leptin works remarkably well to give the brain a good indication of how much food has been eaten; 99.9 percent of the time it balances food intake with energy use," he says. "The problem is that no machine works 100 percent of the time, and that slight bit of inefficiency can lead to extra body weight."

Obesity results when the brain becomes "deaf" to the leptin signal, so one goal of Montminy's research is to "try to make a way to make sure the brain signals are being heard." But to do that, he and his research team first have to understand all of the signals involved in the satiety pathway.

Through years of research, they have uncovered a family of genes that act as energy switches, turning other genes on or off. One gene, TORC2, acts like a fasting switch that flips on the production of glucose in the liver when blood glucose levels run low, usually during sleep. During the day, the hormone insulin normally shuts down TORC2, ensuring that blood sugar levels don't rise too high. Problems along the pathway, however, can help lead to diabetes.

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http://www.physorg.com/print139410100.html

Scientists have found a protein that can promote the burning of body fat – a discovery that could lead to new ways to tackle obesity.

Mice injected with a protein called BMP7 increased their production of "good" brown fat cells, while keeping their levels of the normal white fat cells constant.

Fat is a crucial part of the body's regulation of metabolism and body temperature. There are two types of fat cell with different functions: the well-known white fat cells, which store energy and contribute to obesity, and lesser-known brown fat cells that burn calories to generate body heat.

Though people are born with a good supply of brown fat cells, these are usually lost after infancy. Reintroducing brown fat could therefore increase the amount of energy a person burns.

In their experiments, Yu-Hua Tseng's team at the Joslin Diabetes Centre at Harvard Medical School looked at the factors that determine the amounts of different types of fat cell in the body. They identified a protein called BMP7 which promotes the creation of brown fat. Without it, the amount of brown fat in mice ran low.

When the protein was administered artificially, it boosted the amount of brown fat and left the white fat unchanged. The results are published today in Nature.

"As we learn more about the controls of brown fat development, medical interventions to increase energy expenditure by brown fat inducing agents, such as BMP7, may provide hope to these individuals in losing weight and preventing the metabolic disorders associated with obesity," said Tseng.

A separate study led by Bruce Spiegelman at the Dana-Farber Cancer Institute in Massachusetts found that brown fat cells can be made from the same precursor tissue that normally produces muscle cells.

Spiegelman found that a molecular switch called PRDM16 regulates the creation of brown fat from immature muscle cells. Turning off the switch in the lab converted brown fat in mice into muscle cells.

Both studies are published in this week's issue of the journal Nature.

"Brown fat can increase energy expenditure and protect against obesity," Spiegelman writes. "The epidemic of obesity, closely associated with increases in diabetes, hypertension, hyperlipidemia, cancer and other disorders, has propelled a major interest in adipose cells and tissues."

Read the rest of the article:

http://www.guardian.co.uk/science/2008/aug/21/brown.fat.obesity/print