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.
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C Ruth González, María J Vázquez, Miguel López, and Carlos Diéguez
R M Señarís, M D Lewis, F Lago, F Domínguez, M F Scanlon, and C Diéguez
ABSTRACT
The effects of free fatty acids on somatostatin secretion, content and mRNA levels in fetal rat hypothalamic and cortical cell cultures were investigated. Somatostatin secretion and content were quantified by radioimmunoassay. Somatostatin mRNA levels were measured by Northern blot hybridization using a cRNA probe. Treatment with either caprylic acid (5×10-3 m) or oleic acid (5× 10-5 m) for 90 min inhibited basal somatostatin secretion in both hypothalamic and cortical cell cultures. In addition, the increase in somatostatin secretion induced by incubation with veratridine (10-4 m) or carbachol (10-4 m) for 90 min was significantly reduced by the addition of caprylic acid, but somatostatin release stimulated by 5·6×10-2 m KCl was not affected. Furthermore, treatment with these free fatty acids for 90 min markedly decreased somatostatin mRNA levels in both types of neurone culture. These inhibitory effects were transient, being observed after 90 min, but not after 5 h. These results support the probability that there is a role for free fatty acids in the regulation of somatostatin mRNA levels and somatostatin secretion in both hypothalamic and cortical cell cultures.
C V Alvarez, J B Zalvide, E Cancio, C Dieguez, B J Regueiro, F V Vega, and F Dominguez
ABSTRACT
Using flow cytometry we observed the effects that different hormonal treatments had on the progression of rat thyroid (FRTL-5) cells through the cell cycle. The absence of hormones or the addition of TSH (6 mU/ml) did not induce DNA synthesis; however, the addition of IGF-I (30 ng/ml) promoted cell proliferation. The number of cells recruited by IGF-I was lower than when IGF-I and TSH were used. We therefore concluded that we had a model with three different types of cells: (1) quiescent cells, cells cultured in the absence of hormones, considered to be G0-arrested cells, (2) competent cells, TSH-treated cells that did not proliferate (being arrested in a cycle phase different from G0) and (3) actively proliferating cells, cells treated with TSH plus IGF-I.
Prothymosin α (PTA) mRNA levels were almost undetectable in cells cultured without hormones at all times studied, i.e. 8, 14 and 24 h. On the contrary, TSH and/or IGF-I greatly increased PTA mRNA. These data indicate that G0-arrested quiescent cells do not express PTA mRNA and that PTA mRNA is induced when FRTL-5 cells are committed to proliferate by the addition of TSH, in spite of being arrested by the lack of IGF-I. We therefore conclude that PTA mRNA expression may be an event that is necessary for cells to proliferate, but that it is not sufficient for the promotion of cell progression through the cell cycle.
