Mechanism of Increased Appetite Stimulation in Obese Individuals

Obese individuals often have increased appetite despite normal and lower plasma levels of the main appetite stimulant hormone ghrelin…. 

Although obesity is commonly associated with increases in hunger and food intake, the concentrations of ghrelin, the principal hunger hormone, are not always elevated in these individuals. This suggests that in obesity ghrelin may transmit even more powerful hunger signals to the central circuitries regulating appetite. Ghrelin administration has been shown to stimulate food intake more efficiently in obese than in lean humans but the mechanism of ghrelin’s effect in obese individuals has been previously unknown.

In this study, researchers highlighted the presence of specific antibodies, or immunoglobulins, in the blood of obese patients, antibodies that recognise ghrelin and regulate appetite. They suggest that plasma ghrelin-reactive IgG antibodies serve as carrier proteins that may enhance the bioactivity of endogenous or exogenous ghrelin. The biologically available IgG-bound fraction of circulating ghrelin was increased in obese patients when compared to non-obese individuals. By binding to ghrelin, the immunoglobulins protect the hunger hormone from being broken down rapidly in the bloodstream. The ghrelin can then act on the brain for longer and stimulate appetite. In the study, the co-administration of ghrelin together with IgG from obese individuals, but not with IgG from anorectic or control patients, increased food intake in rats. Similarly, chronic injections of ghrelin together with IgG from genetically obese mice increased food intake, meal frequency and total lean body mass of mice.

In conclusion, the authors found that plasma ghrelin is normally bound to circulating IgG, which may have a role as a carrier for the hormone protecting it from degradation and further that IgG from obese patients seem to bind more ghrelin than IgG from non-obese subjects. They also said that IgG from both obese humans and genetically obese mice display elevated micromolar affinity for ghrelin, which may be responsible for an increased ability of these IgG to transport ghrelin and thus enhance its orexigenic and anabolic actions.

• The biologically available IgG-bound fraction of circulating ghrelin was increased in obese patients when compared to non-obese individuals.
• In obesity, ghrelin may transmit even more powerful hunger signals to the central circuitries regulating appetite.
• Similarly, chronic injections of ghrelin together with IgG from genetically obese mice increased food intake, meal frequency and total lean body mass of mice.

Nature Communications, October 2013