Wednesday, February 24, 2010

Ghrelin and Gastric Bypass

Ghrelin (pronounced GRELL-in) is a peptide, a type of chemical compound. It was first discovered and named by Japanese researchers led by Masayasu Kojima in 1999. Ghrelin is produced in the stomach and has been shown to stimulate the release of growth hormone in humans and rats. It also increases appetite and, thus, food intake.

Research by Cummings, et al has also shown that ghrelin levels fluctuate throughout the day, increasing before meal time and decreasing after eating. In addition, when one is restricting food intake, ghrelin production increases. It may thus be implicated in the battle we have to keep weight off. As soon as we lose some weight, ghrelin is working overtime to make us gain it back. Ghrelin appears to participate in a homeostatic process described by "set point" theory.

Cummings and his associates also compared ghrelin levels in the blood of dieters, gastric bypass patients, and normal controls. As they expected, the fluctuation of ghrelin in the dieters and the normal controls followed a similar pattern, peaking before meals and dropping afterward. Also as expected, the dieters produced more ghrelin after a 6-month weight loss program than they did before the program.

A new finding was that gastric bypass patients (9 to 31 months after surgery) had ghrelin levels scarcely above the detectable limit, with barely any peaks and valleys. In other words, their ghrelin production was at a consistently low level throughout the day and overnight. Could this account for the descriptions these patients gave of the abrupt change in appetite and food choices they experienced immediately after surgery? Could a sudden decrease in ghrelin production explain the "honeymoon" period after gastric bypass?

A word about the "honeymoon" period . . . Clinicians and researchers have been fascinated, and surgical candidates have been lured, by descriptions of the post-surgical state known as the "honeymoon" period. Of course, patients eat less because their stomachs are a fraction of their former size. But, as if by magic, patients also report a new willingness to eat fruits, vegetables, low-fat dairy products and whole grains. They seem to naturally avoid high-fat foods like red meat and chocolate cake. Many report a phenomenon they never dreamed possible . . . feeling satisfied with a single taste of a craved food (say, cheesecake) and then throwing the rest away.

Alas, the explanation of the "honeymoon" period is not so simple as we might wish. Further studies have showed different results regarding the amount of ghrelin produced before and after gastric bypass. And there is also a likelihood that, even if gastric bypass does decrease ghrelin levels, this result is not permanent. Honeymoons don't last forever, in marriage, politics or gastric bypass. Alas.

More on ghrelin and other "gut hormones" in the next post.
Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, & Kangawa K (1999). Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature, 402 (6762), 656-60 PMID: 10604470

Cummings, D. (2002). Plasma Ghrelin Levels after Diet-Induced Weight Loss or Gastric Bypass Surgery New England Journal of Medicine, 346 (21), 1623-1630 DOI: 10.1056/NEJMoa012908