Intestine more important than stomach for ghrelin action?

[Guest guest]

Hi All,

It seems to me that the actions of ghrelin, the appetite-increasing

hormone, may require acylation for some of its actions.

Why does this matter?

A new pdf-available-to-all paper that uses CR as a control, and

is therefore of special interest in my view, suggests that the small

intestine plays a large role in the action of ghrelin by acylating

the hormone. The benefits are only for the obese animals, though.

For a background on ghrelin generally, there is:

" The acylated peptide

specifically releases GH both in vivo and in vitro, and O-n-

octanoylation at

serine 3 is essential for the activity. We designate the GH-releasing

peptide

'ghrelin' (ghre is the Proto-Indo-European root of the word 'grow'). "

in

http://tinyurl.com/4pta

and

" neuroendocrine but not all other ghrelin actions are dependent on

acylation in serine 3 "

in

http://tinyurl.com/5ftr5

From the new paper,

Rubino F, Zizzari P, Tomasetto C, Bluet-Pajot MT, Forgione A, Vix

M,

Grouselle D, Marescaux J.

The Role of the Small Bowel in the Regulation of Circulating

Ghrelin Levels and

Food Intake in the Obese Zucker Rat.

Endocrinology. 2004 Dec 29; [Epub ahead of print]

PMID: 15625244 [PubMed - as supplied by publisher]

http://endo.endojournals.org/cgi/rapidpdf/en.2004-1181v1

comes:

" Ghrelin is a 28-aminoacid residue peptide predominantly produced

by

enteroendocrine cells in the oxyntic mucosa of the stomach 18,19,26 .

The acylation of one

of its serine residues seems to have importance for its endocrine

actions 27,28 , but the

unacylated form has also been shown to possess metabolic effects 29 .

In both humans

and rodents, ghrelin levels are increased by food deprivation and are

decreased post-prandially ... "

" Consistently with previous reports 30 , this study found that in

obese Zucker rats

refeeding is associated with a paradoxical 30% increase of acylated

ghrelin levels over

fasting concentrations, suggesting that these obese animals are

resistant to the meal-induced

decrease of circulating acylated ghrelin. English and co-workers 31

reported that

food intake fails to suppress plasma ghrelin levels also in obese

humans. This altered

endocrine response to eating in obese subjects may contribute to

overeating and have

implications for anti-obesity therapies. Indeed, interventions on the

dynamic response of

ghrelin to eating, which seems to be altered in rodent and human

obese subjects, may be

a more effective way to fight obesity. ... "

For abbreviations, these were:

duodenal-jejunal bypass (DJB), Roux-en-Y gastric bypass (RYGB),

gastric restriction (GB),

Of note for me from the pdf are:

...Interventions

Zucker ZDF rats underwent one of DJB, Gastric Banding (GB) and

Sham operations.

Normal controls underwent either DJB or the sham operation.

A further group of age-matched Zucker rats underwent food

restriction to provide a model of diet-induced weight loss.

... Zucker rats undergoing marked food restriction achieved a

decrease in weight gain that

was comparable to that of DJB (6.6+0.6 % vs 5.2+5.3 % respectively;

P=NS). Hence,

this group of rats was an appropriate control for comparing the

hormonal effect of diet-induced

weight loss vs surgically induced weight loss.

... To investigate whether the effect of DJB on the ghrelin

response to feeding was a

specific outcome of the bypass of the proximal bowel and not

secondary to the

reduction of weight gain induced by the procedure, we tested the

effect of diet-induced

weight loss on circulating ghrelin in a group of matched Zucker rats

undergoing food

restriction for 4 weeks. In spite of similar degree of weight gain

compared to DJB rats

the diet group of animals maintained the paradoxical increase of

acylated ghrelin in

response to feeding (330±9 vs 218±23 pg/ml; P<0.01).

... Furthermore, there was

no difference in leptin levels in these rats after DJB-induced or

diet-induced weight loss

suggesting that there was no direct impact of DJB on leptin secretion.

... However, in obese Zucker rats the operation reversed the

altered response of

circulating acylated ghrelin to feeding. The specificity of this

result is demonstrated by

the lack of such an effect in GB-treated and sham operated Zucker

rats as well as in the

group undergoing diet.

...

Cheers, Alan Pater