Genetic variation of the ghrelin activator gene ghrelin O-acyltransferase (GOAT) is associated with anorexia nervosa.

The gastrointestinal peptide hormone ghrelin promotes food intake and increases body weight and adiposity through activation of the growth hormone secretagogue receptor (GHSR1a). To promote its biological action ghrelin is acylated at its serine 3 residue by the recently discovered ghrelin O-acyltransferase (GOAT, a.k.a. membrane-bound O-acyltransferase 4, MBOAT4). Plasma levels of total and acyl-ghrelin are negatively correlated with body-mass-index (BMI); as lower the BMI as higher plasma levels of total and acylated ghrelin and vice versa. Accordingly, plasma levels of total and acyl-ghrelin are elevated in patients with anorexia nervosa (AN) and decline upon weight regain. The importance of the endogenous Goat/ghrelin system in the neuroendocrine adaptation to fasting was recently highlighted by the observation that acyl-ghrelin mediated elevation of growth hormone (GH) release prevents starvation induced hypoglycemia in Goat(-/-) mice. The aim of this study was to test if genetic variation of GOAT is implicated in the etiology of AN. We therefore assessed association of 6 tagging single nucleotide polymorphisms (tagSNPs), which were predicted to cover 96% the common genetic variability of GOAT plus 50 kb of the 5' and 3' flanking region, in 543 German patients with AN and 612 German normal and underweight healthy controls. Based on a recessive mode of inheritance we observed some evidence for association of the G/G genotype at SNP rs10096097 with AN (nominal two-sided p = 0.031). Based on our results we conclude that genetic variation in GOAT might be implicated in the etiology of AN.

The influence of eating behavior and eating pathology on weight loss after gastric restriction operations.

BACKGROUND: Eating behavior before surgery is considered to have great predictive value for the course of weight after surgery. The present study investigates the predictive value of three dimensions of eating behavior and disturbed eating on weight loss after gastric restriction surgery. METHODS: 149 patients consisting of 47 males (32%), 102 females (68%), with mean age 38.8+10.3 years, were investigated by means of a structured interview and the Three Factor Eating Questionnaire (TFEQ) before (T1) and at least 12 months after (T2) (14.0+1.5 months) gastric restriction surgery. RESULTS: Mean BMI before surgery was 50.9+/-8.1 kg/m2; postoperatively, the BMI decreased on average by 12.8 kg/m2 to 38.6+/-6.8 kg/m2 (t=22.7, P=0.000) at T2. Point-prevalence of Binge Eating Disorder (BED) according to DSM-IV was 2.0%, and lifetime-prevalence 7.4%, respectively. Of our sample, 20.1% reported current binge episodes without fulfilling all criteria for BED. An eating pathology consisting of continual eating ("grazing") was reported in 19.5% of the patients. At T2, patients with a weight loss of at least 25% of their pre-surgery weight indicated significantly less hunger and disinhibition compared with patients with less weight loss. Patients with a distinct craving for sweets after surgery lost significantly less weight. Patients with binge episodes or "grazing" before surgery did not differ in average weight loss from patients without binge episodes or "grazing". CONCLUSION: Postoperative but not preoperative eating behavior is of predictive value for the extent of weight loss after gastric restriction surgery.