Changes in Acyl Ghrelin, Des-acyl Ghrelin, and Ratio of Acyl Ghrelin to Total Ghrelin with Short-term Refeeding in Female Inpatients with Restricting-type Anorexia Nervosa

Abstract

Restricting type of anorexia nervosa (AN-R) is a serious disorder affecting adolescents and young adults and decreases quality of life over a long period. Successful weight restoration is an important prognostic factor for disease outcome; however, the underlying mechanism of refeeding resistance, a core psychopathology relevant to 'ambivalent' eating behaviors, remains unclear in this disorder. Ghrelin plays an important role in the regulation of growth hormone release, appetite, and energy metabolism. However, the early progress of these patients and changes in the levels of acyl ghrelin and des-acyl ghrelin during treatment were not reported. The purpose of this study was to determine the changes in ghrelin levels (acyl and des-acyl) during early treatment. As a result, des-acyl ghrelin in AN-R patients is higher than in control subjects before the therapy, but it decreases with treatment. The plasma des-acyl ghrelin level in AN-R patients started decreasing more rapidly and in early stage of the hospitalization than ever reported, and after 8 weeks, it is significantly lower than in control subjects. It means that des-acyl ghrelin is sensitive and changeable with their nutrition state. Furthermore, the ratio of the acyl ghrelin to total ghrelin increases with 8 weeks treatment. Eight weeks after, energy intake of the AN-R patients is recovered near the normal range with a daily energy intake of 1 700+/-93.54 kcal. These findings may be valuable for future AN-R treatments in order to increase acyl ghrelin and decrease des-acyl ghrelin, thereby influencing the refeeding outcome.

Abnormal relationships between the neural response to high- and low-calorie foods and endogenous acylated ghrelin in women with active and weight-recovered anorexia nervosa

“…Consistent with previous investigations (Germain et al, 2007, 2010; Koyama et al, 2010), we found elevated fasting acylated ghrelin in women with AN. Importantly, our data in AN-WR women, who showed statistically similar acylated ghrelin levels to AN women (both raw values and values after log transformation), indicate persistent ghrelin abnormalities even after long-term weight gain to a healthy level, suggestive of a trait characteristic of AN.…”

“…Secretion of ghrelin, a critical hormone in the complex circuitry responsible for signaling human appetite, is elevated in AN (Germain et al, 2007, 2010; Koyama et al, 2010). Ghrelin signaling is involved in both homeostatic and hedonic pathways, both of which have been shown to be disrupted in individuals with AN (Ellison et al, 1998; Wagner et al, 2007, 2008; Fladung et al, 2010; Gizewski et al, 2010; Frank et al, 2012; Holsen et al, 2012).…”

“…Females with active AN demonstrated elevated total (acylated+des-acylated) ghrelin in a fasted state (Misra et al, 2004; Janas-Kozik et al, 2007; Monteleone et al, 2008; Karczewska-Kupczewska et al, 2010; Sedlackova et al, 2011), in response to a mixed meal (Nakahara et al, 2007; Sedlackova et al, 2011, 2012) and in the 24-h circadian profile (Germain et al, 2007, 2010), which has been shown to be due to increased secretory burst mass and amplitude (Misra et al, 2005). Excessive secretion of acylated ghrelin has also been reported in women with AN (Germain et al, 2010; Koyama et al, 2010). Short-term weight gain in AN is generally associated with decreases in overnight total ghrelin secretion (Misra et al, 2005), and in fasting (Janas-Kozik et al, 2007) and postprandial (Otto et al, 2005) levels of total ghrelin, with most studies focused on changes within individuals in the symptomatic AN group, limiting the ability to examine normalization following treatment.…”

Endocrine consequences of anorexia nervosa

“…In healthy individuals, ghrelin levels increase immediately before meals, and nadir about 30 minutes after food intake 61 . Higher fasting and overnight ghrelin levels have been reported in AN 34, 42, 62 , associated inversely with BMI, fat mass, and insulin. Studies have reported differences in ghrelin levels in restrictive vs. binge-purge forms of AN (AN-R vs. AN-BP) vs. bulimia nervosa (BN), with ghrelin levels (compared to controls) being higher in AN-R 59, 60 , unchanged in BN 59 , and lower in AN-BP 60 .…”

MECHANISMS IN ENDOCRINOLOGY: Ghrelin: the differences between acyl- and des-acyl ghrelin

“…The story of des-acyl ghrelin (DAG; Fig. 1) also began in 1999, when Kojima et al described this peptide in the same report that introduced ghrelin to the scientific world (1,2). The preproghrelin gene-derived peptides include acyl ghrelin (AG), DAG, and obestatin.…”