Obestrin® ITCES Background Research

Obestatin, A New Physiological Opponent of Ghrelin

Circulating obestatin levels in normal subjects and in patients with impaired glucose
regulation and type 2 diabetes mellitus

Background
Obestatin is a novel hormone that is encoded by the Ghrelin gene and produced in the gut.
Ghrelin is profoundly orexogenic and adipogenic, increasing food intake and body weight. This
new ghrelin-associated peptide behaves as a physiological opponent of ghrelin.

Objective
In this study we investigate whether plasma obestatin level is different in patients with impaired
glucose regulation (IGR) and type 2 diabetes mellitus (T2DM). Patients and measurements
Forty-seven patients with T2DMu, 30 subjects with IGR, and 38 sex- and age-matched normal
controls participated in the study. Plasma obestatin levels were measured with a
radioimmunoassay (Phoenix Pharmaceuticals, Inc.). The relationship between plasma obestatin
levels and anthropometric and metabolic parameters was also analysed.

Results
Plasma obestatin levels were lower in patients with T2DM and IGR than in controls (37.5 +/- 9.2
ng/l and 39.2 +/- 9.7 ng/l vs. 43.8 +/- 8.0 ng/l, P = 0.002 and P = 0.039, respectively). Decreasing
concentrations of obestatin were independently and significantly associated with IGR and
T2DM. Multiple logistic regression analysis revealed obestatin to be independently associated
with IGR and T2DM. In a multiple linear regression analysis, only waist-to-hip ratio and
homeostasis model assessment of insulin resistance (HOMA-IR) were independently associated
with plasma obestatin level.

Conclusion
Our results suggest that obestatin may play a role in appetite regulation in patients with IGR and
T2DM.

Qi X, Li L, Yang G, Liu J, Li K, Tang Y, Liou H, Boden G.

Clin Endocrinol (Oxf). 2007 Apr;66(4):593-7
 November 11, 2005

In Study, Obestatin Reduced Appetite in Mice

By DENISE GRADY

Hungry or full, fat or thin: it is mostly a matter of hormones, dozens of them, carrying messages
between the digestive tract, the fat cells and the brain. Eat. Don't eat. Burn calories. Store fat.

Today, researchers at Stanford University are reporting that they have found a previously
unknown member of this chemical cascade, a hormone with a much coveted power: it sharply
reduces the desire to eat.

The new substance, which the scientists named obestatin (OHB-statin), is made in the stomach
and small intestine, and it seems to prompt the brain to send out a signal that says "eat less."

Mice given the hormone for eight days ate half as much as usual and lost weight, the researchers
are reporting today in the journal Science. The hormone seems to reduce hunger in part by
slowing the passage of food through the stomach and small intestine.

The study's director, Dr. Aaron Hsueh, said obestatin had not yet been studied in people and had
been tested only in mice.

But Stanford issued a statement saying Johnson & Johnson, which sponsored the research, has
rights to the discovery. With obesity rates shooting up worldwide, drug companies are
scrambling to develop weight-loss drugs, especially appetite suppressants.

Dr. David E. Cummings, an obesity researcher at the University of Washington, Seattle, who
was not involved in the obestatin study, said, "The chances that this is going to hold up in
humans are very high."

Other researchers are eager to study the molecule. Dr. Cummings said that as soon as he heard
about it he began trying to reach Dr. Hsueh to propose that they work together to measure its
levels in humans.

One thing that especially fascinates scientists about obestatin is its link to another hormone,
ghrelin, which makes people hungry - the opposite of obestatin.

The scientists were surprised to find that the two hormones were products of the same gene. The
gene directs cells to make one protein molecule, which breaks into two smaller ones, called
peptides. One is ghrelin, and the other is obestatin.

The same gene is found in at least 11 species of mammals, Dr. Hsueh and his colleagues
reported, indicating that its role in controlling food intake must be important for survival.