β-Oxidation in ghrelin-producing cells is important for ghrelin acyl-modification

Area of Science:

• Endocrinology
• Metabolism
• Gastroenterology

Background:

• Ghrelin, a peptide hormone produced in the stomach, regulates energy homeostasis and gastrointestinal motility.
• Acyl-ghrelin, the active form, is modified by a fatty acid, but its source is unclear.

Purpose of the Study:

• To investigate the endogenous source of medium-chain fatty acids required for ghrelin acylation.
• To elucidate the mechanism of fatty acid supply for ghrelin modification.

Main Methods:

• Experiments in mice using fat-free diets and antibiotic treatments to deplete intestinal microbiota.
• RT-PCR analysis of pancreas-derived ghrelinoma (PG-1) cells.
• Treatment of PG-1 cells with a carnitine palmitoyltransferase-1 (CPT-1) inhibitor.

Main Results:

• Neither a fat-free diet nor microbiota depletion affected acyl-ghrelin levels in mice.
• PG-1 cells express genes for fatty acid synthesis, metabolism, and transport.
• CPT-1 inhibition significantly reduced acylated ghrelin but not ghrelin or GOAT mRNA levels.

Conclusions:

• The medium-chain fatty acid for ghrelin acylation is likely synthesized within ghrelin-producing cells.
• This synthesis occurs through beta-oxidation of long-chain fatty acids supplied from circulation.
• Intestinal microbiota and diet are not the primary sources for ghrelin acylation.