вход по аккаунту


Active ghrelin levels across time and associations with leptin and anthropometrics in healthy ache Amerindian women of Paraguay.

код для вставкиСкачать
Short Report
Active Ghrelin Levels Across Time and Associations with Leptin and
Anthropometrics in Healthy Ache Amerindian Women of Paraguay
Reproductive Ecology Laboratory, Department of Anthropology, Yale University, New Haven, Connecticut 06520-8277
Rutgers University, New Brunswick, New Jersey 08901
Department of Anthropology, Harvard University, Cambridge, Massachusetts 02138
Active (acylated) ghrelin is a peptide hormone secreted primarily by the stomach, positively associated
with fasting, orexigenic, and promotes growth hormone secretion. It is therefore important to energy intake management. The objective of this pilot research was to (1) compare active ghrelin with previous measurements of leptin and
anthropometrics; (2) assess the consistency of active ghrelin across time in this population; (3) extend our understanding of potential population variation in active ghrelin. Two serum samples separated by 10 days at the same time
between meals were collected from healthy Ache women (n ¼ 12, mean age 32.2 6 14.0 SD) to determine consistency
over time, associations with leptin, and anthropmetric values. Mean active ghrelin was 72.9 6 23.0 pg/ml, highly correlated (r2 ¼ 0.95, P < 0.0001) between collections, and showed no paired mean differences (P < 0.18). There was no
significant correlation with leptin, age, or anthropometric measures. Active ghrelin appears to be consistent over
time in this population, perhaps reflecting regimented meal schedules and less interpopulation variation compared to
leptin. Am. J. Hum. Biol. 20:352–354, 2008.
' 2007 Wiley-Liss, Inc.
Active (acylated) ghrelin is a peptide hormone secreted
primarily by the stomach and serves as an orexigenic signal to the hypothalamus and is a useful biomarker of hunger and satiation (Kojima and Kangawa, 2005). Active
ghrelin differs from its alternate form, total ghrelin in
that active maintains a N-octanoyl group at the Ser3 position that is believed to be necessary for bioactivity. Related
metabolic hormones such as leptin exhibit a broad range
of variation across populations, with values generally
lower in non-western populations after controlling for adiposity (Bribiescas, 2001). Despite the possibility of significant nonpathological population variation in metabolic
hormones, only a limited number of investigations have
explored population variation in total ghrelin profiles
(Shukla et al., 2005) and to our knowledge, none have investigated population variation in the active n-octanoylated active form.
This pilot investigation addresses two preliminary questions that are meant to guide future field investigations.
First, are active ghrelin levels associated with leptin and
anthropometric measures assessed in a previous investigation (Bribiescas, 2001)? Second, it would be useful to establish the consistency of active ghrelin in samples taken
under similar conditions but separated by a significant
amount of time to determine the efficacy of active ghrelin
in investigations that may wish to incorporate a biomarker
of hunger in human ecology research. Ache meal regimens
in this community are believed to be somewhat regimented.
Therefore, active ghrelin values measured at the same time
of day, between meals, should be similar within individuals.
Ache females were recruited from the community of
Puerto Barra, a protestant mission located in the province
of Alto Parana in eastern Paraguay as part of a larger
investigation of the effects of ecological conditions on endocrine function. This community consists of about forty
C 2007
Wiley-Liss, Inc.
households subsisting mostly on manual and mechanical
agriculture with limited hunting in the surrounding forest. Descriptions of Ache ecology and demography have
been described elsewhere (Hill and Hurtado, 1996). Subjects were recruited in exchange for a communal gift.
Because active ghrelin can degrade rapidly (Hosoda
et al., 2004), a brief synopsis of collection, storage, and
handling methods is presented. Blood samples were collected using standard phlebotomy in SST vacuum tubes
with a clotting activator (Vacutainer no. 6514, BectonDickinson, Franklin Lakes, NJ). No anticoagulants were
used. Samples were frozen immediately after serum separation and collection, and stored at 208C. Some partial
thawing may have occurred during shipment on blue ice
but visual inspection upon arrival at the Yale Reproductive Ecology Laboratory confirmed no complete thaw. One
confirmed thaw cycle occurred during leptin assessment
with remaining serum kept at 808C until the measurement of active ghrelin. According to Hosoda et al. (2004),
one freeze thaw cycle results in (100 6 4.0)% active ghrelin recovery and (89.8 6 2.7)% with two freeze thaw cycles
using an assay without acidification (the assay method
used in this study as directed by the manufacturer). Since
this investigation primarily reports within subject variation (day 1 to day 10) in which all samples were treated
identically, collection, storage, and handling methods are
not believed to have resulted in significant degradation.
Subjects had eaten their morning meal before 8 am and
had not eaten since. Samples were collected between 11
and 12 pm, prior to their midday meal resulting in a 3–4 h
*Correspondence to: Richard G. Bribiescas, Department of Anthropology, Yale University, New Haven, CT 06520-8277, USA.
Received 23 April 2007; Accepted 24 April 2007
DOI 10.1002/ajhb.20699
Published online 26 December 2007 in Wiley InterScience (www.interscience.
TABLE I. Summary of means and day 1 active ghrelin associations
with day 10 values, leptin, age, and anthropometrics
Mean 6 SD
Active ghrelin day 1 (pg/ml) (n ¼ 12)
Active ghrelin day 10 (n ¼ 11)b
Leptin (pg/ml)
Fat (%)
Weight (kg)
Height (cm)
76.0 6 18.2
72.9 6 23.0
5.6 6 3.2
33.3 6 4.4
55.2 6 7.4
147.6 6 5.4
25.2 6 1.9
32.2 6 14.0
0.95 (0.0001)
0.12 (0.27)
0.16 (0.20)
0.13 (0.26)
0.08 (0.37)
0.11 (0.29)
0.51 (0.83)
The values within parentheses indicate the P values.
One assay value was unreadable thereby yielding 11 comparison pairs for
regression analysis.
fast. Other investigations have shown that similar periods
of short in-between meal fasting is sufficient to elevate
ghrelin levels (Leidy and Williams, 2006). The 10-day separation between sample collection was conducted for experimental and logistical reasons. This allowed for en
masse, communal sample collection and a more thorough
control of diurnal variation and snacking. It also evoked a
sufficient amount of time in which each sample collection
could be viewed as physiologically independent. That is,
active ghrelin values during the second collection were
not likely to be influenced by levels during the initial collection. This protocol was approved by the Yale University
Committee for the Protection of Human Subjects.
Active ghrelin was assessed using an iodine 125-based
radioimmunoassay kit specific for the octanoylated active
form (GHRA-88HK, Linco Research, St. Louis, MO). All
samples were run in a single assay and quality controls
were within the manufacturer specifications. Anthropometric assessments were conducted using previously validated and described methods (Bribiescas, 2001). Associations between Ache active ghrelin, leptin, fat %, weight,
height, age, and body mass index (BMI) were analyzed
using linear regression. Intraindividual comparisons of
active ghrelin were performed using linear regression and
paired t tests. Results were calculated using Prism 4.0 statistical software for the Macintosh (GraphPad Software,
San Diego, CA). a was set at 0.05.
A summary of ghrelin and other variables is reported in
Table 1. Active ghrelin measurements separated by 10
days were highly correlated, suggesting that active ghrelin exhibits limited variation within subjects (Fig. 1). No
significant intraindividual differences were noted between
the 2 weeks (paired t test 1.45, P < 0.18). Correlations
between active ghrelin, leptin, and anthropometric measurements were not significant.
The hypothesis that active ghrelin should be consistent
across time was supported. However, the tight association
between active ghrelin values across the two sampling
periods was especially noteworthy. While it was assumed
that values should be somewhat similar, more variation
was expected since random snacking and drinking yerba
mate (a common South American tea) between the subjects’ morning and midday meal could not be totally controlled. This implies that either Ache eating habits within
this community are very regimented or that active ghrelin
Fig. 1. Active ghrelin levels in Ache women from samples collected
10 days apart (r2 ¼ 0.95, P < 0.0001).
within this population exhibits a narrow range of variation. Total ghrelin measurements taken every 20 min in
healthy well-fed European individuals during a 24-h fast
suggests modest circadian variation with small rises
around the common time period of meals (Natalucci et al.,
2005). However, caution is warranted in extrapolating
these results to other populations, since Salbe et al. (2004)
reported that Pima Amerindians of Arizona exhibited
ghrelin levels that were twice as high compared to nonPimas even after controlling for caloric intake, energy expenditure, and anthropometrics. Future investigations
among the Ache would aim to measure active ghrelin
before and after an overnight fast. Progress has been
made in developing noninvasive strategies of assessing
ghrelin but more work is necessary (Aydin et al., 2005).
The lack of association between active ghrelin and
anthropometrics was dissimilar from other investigations
(Monti et al., 2006), perhaps resulting from less anthropometric variation among the Ache. Because of sample volume limitations, it was not possible to assess male ghrelin
although Ache male leptin suggests that population variation in metabolic hormones extend to men also (Bribiescas
and Hickey, 2006).
Ghrelin may also vary in association with menstrual
cycles. Menstrual phases were not known in this study
but the consistency of values within individuals makes
menstrual cycle timing an unlikely source of variation.
Interestingly, ghrelin values are elevated in exercising
amenorrheic women (De Souza et al., 2004) but only marginally associated with daily energetic expenditure in
healthy women (St-Pierre et al., 2004). This is noteworthy
in light of the fact that Ache women are also very physically active in conducting their daily chores and energetically demanding tasks.
Post hoc comparisons with mean values from other
active ghrelin measurements reported in the literature
(Nakai et al., 2003) suggest no significant differences compared to healthy control subjects (P < 0.33) but were significantly lower than anorectic patients (P < 0.03), implying that active ghrelin levels among the Ache do not exhibit similar population differences as observed with
leptin (Bribiescas, 2001, 2005; Bribiescas and Hickey,
American Journal of Human Biology
2006). However, formal comparisons with proper controls
are needed.
This preliminary investigation suggests that the relationship between active ghrelin, leptin, and anthropometrics is not strong. Active ghrelin also appears to be less
variable compared to leptin and may be a universal cue of
feeding and satiety among populations. To our knowledge,
this is the first report of active ghrelin in a developing
population. It would be useful to continue exploring the
utility of ghrelin as an independent biomarker of hunger
in developing populations as well as the development less
invasive methods of assessment.
The authors wish to thank the Ache community of Puerto
Barra, especially Angel Tatunambiangi, Carmen Bywangi,
Bjarne, and Rosalba Fostervold for their cooperation as well
as Richard Lawler for his aid in the field. The authors also
extend our sincere gratitude to Dr. Liza Cariaga-Lo, Dean
of the Yale University Office for Diversity and Equal Opportunity for her support to JB. This research was supported
by a Yale University Junior Faculty Fellowship (RGB) and
a Summer Undergraduate Research Fellowship (JB).
Aydin S, Halifeoglu I, Ozercan IH, Erman F, Kilic N, Ilhan N, Ozkan Y,
Akpolat N, Sert L, Caylak E. 2005. A comparison of leptin and ghrelin
levels in plasma and saliva of young healthy subjects. Peptides 26:647–
Bribiescas RG. 2001. Serum leptin levels and anthropometric correlates in
Ache Amerindians of eastern Paraguay. Am J Phys Anthropol 115:297–
American Journal of Human Biology
Bribiescas RG. 2005. Serum leptin levels in Ache Amerindian females with
normal adiposity are not significantly different from American anorexia
nervosa patients. Am J Hum Biol 17:207–210.
Bribiescas RG, Hickey MS. 2006. Population variation and differences in
serum leptin independent of adiposity: a comparison of Ache Amerindian men of Paraguay and lean American male distance runners. Nutr
Metab (Lond) 3:34.
De Souza MJ, Leidy HJ, O’Donnell E, Lasley B, Williams NI. 2004. Fasting
ghrelin levels in physically active women: relationship with menstrual
disturbances and metabolic hormones. J Clin Endocrinol Metab 89:
Hill K, Hurtado AM. 1996. Ache life history: the ecology and demography
of a foraging people, Vol. 19. New York: Aldine de Gruyter. 561 p.
Hosoda H, Doi K, Nagaya N, Okumura H, Nakagawa E, Enomoto M, Ono
F, Kangawa K. 2004. Optimum collection and storage conditions for
ghrelin measurements: octanoyl modification of ghrelin is rapidly hydrolyzed to desacyl ghrelin in blood samples. Clin Chem 50:1077–1080.
Kojima M, Kangawa K. 2005. Ghrelin: structure and function. Physiol Rev
Leidy HJ, Williams NI. 2006. Meal energy content is related to features of
meal-related ghrelin profiles across a typical day of eating in non-obese
premenopausal women. Horm Metab Res 38:317–322.
Monti V, Carlson JJ, Hunt SC, Adams TD. 2006. Relationship of ghrelin
and leptin hormones with body mass index and waist circumference in a
random sample of adults. J Am Diet Assoc 106:822–828. quiz 829-830.
Nakai Y, Hosoda H, Nin K, Ooya C, Hayashi H, Akamizu T, Kangawa K.
2003. Plasma levels of active form of ghrelin during oral glucose tolerance test in patients with anorexia nervosa. Eur J Endocrinol 149:R1–
Natalucci G, Riedl S, Gleiss A, Zidek T, Frisch H. 2005. Spontaneous 24-h
ghrelin secretion pattern in fasting subjects: maintenance of a mealrelated pattern. Eur J Endocrinol 152:845–850.
Salbe AD, Tschop MH, DelParigi A, Venti CA, Tataranni PA. 2004. Negative relationship between fasting plasma ghrelin concentrations and ad
libitum food intake. J Clin Endocrinol Metab 89:2951–2956.
Shukla V, Singh SN, Vats P, Singh VK, Singh SB, Banerjee PK. 2005.
Ghrelin and leptin levels of sojourners and acclimatized lowlanders at
high altitude. Nutr Neurosci 8:161–165.
St-Pierre DH, Karelis AD, Cianflone K, Conus F, Mignault D, RabasaLhoret R, St-Onge M, Tremblay-Lebeau A, Poehlman ET. 2004. Relationship between ghrelin and energy expenditure in healthy young
women. J Clin Endocrinol Metab 89:5993–5997.
Без категории
Размер файла
66 Кб
women, level, paraguay, acros, ghrelin, anthropometric, ache, health, times, associations, activ, leptin, amerindians
Пожаловаться на содержимое документа