Subject Standardization, Acclimatization, and Sample Processing Affect Gut Hormone Levels and Appetite in Humans

Chandarana, Keval; Drew, Megan E.; Emmanuel, Julian; Karra, Efthimia; Gelegen, Çiğdem; Chan, Pan F.; Cron, Nicholas J.; Batterham, Rachel L.

doi:10.1053/j.gastro.2009.02.047

Cited by 77 publications

(69 citation statements)

References 32 publications

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“…Ten AA and 10 TT overnight-fasted subjects (Supplemental Table 2) underwent a standard test meal study (Supplemental Table 3) using our established protocols ( Figure 1A) (41). Subjective appetite was evaluated using visual analog scales (VASs) (39,41) preprandially, at 20 and 30 minutes following meal ingestion, and every 30 minutes thereafter until 180 minutes postmeal.…”

Section: Resultsmentioning

confidence: 99%

“…Subjective appetite was evaluated using visual analog scales (VASs) (39,41) preprandially, at 20 and 30 minutes following meal ingestion, and every 30 minutes thereafter until 180 minutes postmeal. Simultaneously, blood sampling for the measurement of circulating concentrations of the anorectic hormone, PYY3-36, and the orexigenic hormone, acyl-ghrelin, was undertaken.…”

Section: Resultsmentioning

confidence: 99%

“…Additional exclusion criteria for the fMRI study were: left-handedness, claustrophobia, presence of a hearing aid or ferromagnetic material, food preferences/dislikes inconsistent with our food images, and irregular eating habits. Our established protocols for subject standardization and acclimatization/habituation to the study environment were used (41). Subjects recruited to the fMRI study participated in a simulated scan in a mock-MRI scanner before the first scanning session.…”

Section: Subjectsmentioning

confidence: 99%

“…Fto KO mice (25) and their 20-week-old WT littermates were sacrificed after a 16-hour overnight fast or in the ad libitum fed state (n = 6-9 per group). Blood was collected and processed as previously described (41). Mouse total and acyl-ghrelin plasma levels were determined by ELISA (Millipore).…”

Section: Subjectsmentioning

confidence: 99%

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A link between FTO, ghrelin, and impaired brain food-cue responsivity

Karra

O’Daly

Choudhury³

et al. 2013

J. Clin. Invest.

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342

323

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Polymorphisms in the fat mass and obesity-associated gene (FTO) are associated with human obesity and obesity-prone behaviors, including increased food intake and a preference for energy-dense foods. FTO demethylates N 6 -methyladenosine, a potential regulatory RNA modification, but the mechanisms by which FTO predisposes humans to obesity remain unclear. In adiposity-matched, normal-weight humans, we showed that subjects homozygous for the FTO "obesity-risk" rs9939609 A allele have dysregulated circulating levels of the orexigenic hormone acyl-ghrelin and attenuated postprandial appetite reduction. Using functional MRI (fMRI) in normal-weight AA and TT humans, we found that the FTO genotype modulates the neural responses to food images in homeostatic and brain reward regions. Furthermore, AA and TT subjects exhibited divergent neural responsiveness to circulating acyl-ghrelin within brain regions that regulate appetite, reward processing, and incentive motivation. In cell models, FTO overexpression reduced ghrelin mRNA N 6 -methyladenosine methylation, concomitantly increasing ghrelin mRNA and peptide levels. Furthermore, peripheral blood cells from AA human subjects exhibited increased FTO mRNA, reduced ghrelin mRNA N 6 -methyladenosine methylation, and increased ghrelin mRNA abundance compared with TT subjects. Our findings show that FTO regulates ghrelin, a key mediator of ingestive behavior, and offer insight into how FTO obesity-risk alleles predispose to increased energy intake and obesity in humans.Introduction FTO is an AlkB-like 2-oxoglutarate-dependent nucleic acid demethylase of uncertain cellular function (1). Genome-wide association studies (GWAS) have reliably established that SNPs within the first intron of FTO are robustly associated with increased BMI and adiposity across different ages and populations (2-6). Subjects homozygous for the "obesity-risk" A allele of FTO rs9939609 have a 1.7-fold increased risk for obesity compared with subjects homozygous for the low-risk T allele (2). Evidence to date suggests that the association between SNPs in FTO and BMI is predominantly driven by increased energy intake. Subjects homozygous for the obesity-risk A allele of rs9939609 exhibit overall increased ad libitum food-intake (7-9), particularly fat consumption (7, 9-11), and impaired satiety (12, 13). Furthermore, preschool AA children (AA denotes homozygosity for the A obesity-risk allele in the rs9939609 FTO variant) exhibit obesity-prone eating behaviors, including increased food responsiveness and a tendency to eat in

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Subjectsmentioning

confidence: 99%

Section: Subjectsmentioning

confidence: 99%

See 2 more Smart Citations

A link between FTO, ghrelin, and impaired brain food-cue responsivity

Karra

O’Daly

Choudhury³

et al. 2013

J. Clin. Invest.

Self Cite

342

323

View full text Add to dashboard Cite

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“…Circulating PYY levels increase promptly in response to nutrient ingestion, caloric load, food consistency, and nutrient composition (22,24,25). The initial postprandial rise in circulating PYY occurs within 15 min of food ingestion, before nutrients have reached the L cells of the distal gastrointestinal tract, implying the existence of a neural or hormonal mechanism in this release process.…”

Section: Introductionmentioning

confidence: 99%

Effect of somatostatin infusion on peptide YY secretion: studies in the acute and recovery phase of anorexia nervosa and in obesity

Rigamonti

Cella

Bonomo

et al. 2011

European Journal of Endocrinology

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Objective: Changes in many gastrointestinal peptides, including the anorexigenic peptide YY (PYY), which is produced by L cells, occur in both anorexia nervosa (AN) and obesity (OB). High PYY levels are present in AN, whereas in morbid OB fasting and postprandial PYY secretion is blunted. Somatostatin (somatotropin release-inhibiting factor (SRIF)) reportedly inhibits plasma PYY concentrations in animals and healthy humans, but the effect of a SRIF infusion on spontaneous PYY secretion in AN and OB is unknown. Methods: A total of 18 young women, seven with acute AN (A-AN), four with AN in the recovery phase (R-AN), and seven with morbid OB, were studied. All subjects underwent an infusion of SRIF (9 mg/kg i.v./h, over 60 min), with blood samples drawn before and at different time intervals after SRIF administration. Plasma PYY levels were measured at each time point. Results: SRIF significantly inhibited plasma PYY concentrations in R-AN and OB, without affecting PYY titers in A-AN. In OB, the inhibitory effect of SRIF also persisted at 90 min. Withdrawal of SRIF infusion in R-AN resulted in a prompt restoration of basal plasma PYY levels, whereas termination of SRIF infusion in OB was followed by a slower increase of PYY titers toward baseline levels. After infusion, PYY D area under the curve (DAUC) in R-AN was significantly higher than those in A-AN and OB patients. A significant difference in PYY DAUC between A-AN and OB was present. Conclusions: These results suggest the existence of a hypo-and hyper-sensitivity of L cells to the inhibitory effect of SRIF in A-AN and OB respectively.

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