ADA 2008: Gut hormones key to appetite regulation

Gut hormones play a key and often overlooked role in weight loss and weight regulation. Changes in weight are determined largely by the balance between energy intake and energy expenditure, but gut hormones can affect both sides of the energy equation.

"Bariatric surgery is the only known cure for obesity," said Stephen Bloom, MD, Imperial College London Hammersmith Hospital. "It's expensive, it's dangerous, but it works. But it doesn't work the way you probably think it does."

Many clinicians and patients believe that gastric-reduction surgery reduces weight by restricting food intake. The reality, Dr. Bloom said, is that the procedure works by disrupting digestion, which up-regulates secretion of hormones that induce satiation, which in turn reduces appetite. Bariatric surgery reduces weight because patients want to eat less, not because they must eat less.

The human gut produces a variety of hormones, including ghrelin, peptide YY (PYY), and oxyntomodulin, that can induce feelings of hunger and satiation as well as boost energy expenditure. Ghrelin, for example, is a potent appetite stimulant. It has been used successfully induce appetite and eating in cancer and renal failure patients suffering from cachexia. "We can induce appetite in people who otherwise have no interest in eating," Dr. Bloom said.

PYY functions in the opposite direction to increase satiety. It causes a feeling of fullness after eating and reduces appetite. Secretion is triggered by incomplete digestion or malabsorption. Patients with a gastric bypass are less able to digest and absorb nutrients, which boosts PYY levels and makes them feel full sooner.

Patients with partial ileal resections and digestive disorders such as celiac disease or tropical sprue also absorb poorly. Poorly digested food passing through the intestine triggers PYY secretion, inducing feelings of satiety and loss of appetite. Eating high-fiber foods, which are also poorly absorbed, has a similar effect on PYY and reduces appetite.

Oxyntomodulin reduces appetite and increases energy expenditure. Markedly elevated levels of oxyntomodulin are seen in many bowel disorders such as pancreatic failure, tropical malabsorption and post-surgical short bowel disorder, all characterized by anorexia.

Obese volunteers who self-injected oxyntomodulin 30 minutes before meals showed a 38% decrease in caloric intake and a significant weight over a 4-week trial compared to placebo, Dr. Bloom said. The weight loss was almost entirely adipose tissue. The oxyntomodulin group also showed a 9% increase in energy expenditure over the placebo group.

"When you look at obese people and thin people, what you always see is that thin people are more active," he noted.