Influence of chronic undernutrition and leptin on GOAT mRNA levels in rat stomach mucosa

Abstract

The most unique feature of ghrelin is the acyl-modification of a hydroxyl group of the Ser3 in the N-terminus. The Ser3 is commonly modified by n-octanoic acid in vertebrates being needed for its biological effects, at least in terms of feeding. Therefore, a critical question regarding the role of ghrelin was to characterize the mechanism involved in its acylation. The acyltransferase that catalyzes ghrelin octanoylation has been recently identified and named ghrelin O-acyltransferase (GOAT). The aim of this study was to clarify the physiological implications of GOAT in the regulation of energy balance, by assessing the effect of undernutrition, as well as fasting in adult male rats. We have determined GOAT mRNA expression levels by real time-PCR in the stomach mucosa. Our results show that chronic food restriction led to an increase in GOAT mRNA, particularly following long-term chronic malnutrition (21 days). Furthermore, following 48 h complete fasting, a situation with high-circulating ghrelin levels, we found similar mRNA expression of GOAT in fed and fasted rats; exogenous leptin administration markedly increase GOAT mRNA levels in the stomach mucosa of fasted rats. These findings suggest that increased GOAT mRNA levels may have a role in mediating the physiological responses to chronic undernutrition and could represent an adaptive response to prevent long-lasting alterations in energy balance and body weight homeostasis. Furthermore, our data also offer mechanistic insights into the reason why during fasting acylated ghrelin levels are not increased at a time when a marked increase in an orexigenic signal as important as acylated ghrelin will be expected.

GOAT: the master switch for the ghrelin system?

“…Curiously, Goat mRNA expression remained unaltered in fed and fasted rats. Only fasted rats treated with leptin showed an increase in Goat mRNA expression (61).…”

“…Moreover, the analysis of GOAT mRNA in samples enriched with mouse gastric ghrelin cells has demonstrated a high expression of GOAT within ghrelin cells and a high correlation with ghrelin distribution (60). GOAT mRNA expression was also evaluated in rat tissues which contained a similar pattern of expression observed in human and mouse tissues (61).…”

“…In the case of energy balance, the effect of acute food deprivation and chronic malnutrition on Goat mRNA expression in stomach mucosa from normal male rats was evaluated (61). Despite the changes in body weight caused by chronic malnutrition, Goat mRNA levels remained stable.…”

Ghrelin Gene Products and the Regulation of Food Intake and Gut Motility

“…Chronic undernutrition markedly increased the expression of GOAT mRNA levels in stomach mucosae, offer a mechanistic explanation of the increased acyl ghrelin levels observed in patients with severe malnutrition (Gonzá lez et al, 2008). Using absorbable medium-chain fatty acid, GOAT-ghrelin system could act as a nutrient sensor to tell the brain that high caloric food is available, leading to fat storage, nutrient partitioning, and growth signals (Kirchner et al, 2009).…”

Ghrelin O-acyltransferase (GOAT) and energy metabolism

“…In rats, GOAT mRNA is also expressed in hypothalamus, stomach, intestine, ovary, serum, placenta, muscle, heart, and adrenal glands (Gonzalez et al, 2008). Gutierrez et al (Gutierrez et al, 2008) demonstrated that GOAT transcripts were most abundant in stomach and pancreas in humans.…”