Gut-derived hormones affect appetite. Ghrelin increases hunger and decreases after food intake, whereas satiation and satiety are induced by peptide YY (PYY), glucagon-like peptide-1 (GLP-1), and perhaps glucose-dependent insulinotropic polypeptide (GIP) which are increased after food intake [1-3]. These gut-derived appetite hormones have been theorized to play a role in the weight-loss that results from bariatric surgery [4, 5] and agonists of GLP-1 and GIP receptors have become successful medical treatments for obesity [6-8]. Circulating concentrations of gut-derived appetite hormones can be influenced by dietary macronutrient composition [9-13], which provides a theoretical basis for why some diets may help facilitate weight loss better than others. We investigated inpatient adults in a randomized crossover study and demonstrated that, after 2 weeks of eating a low carbohydrate (LC) diet (75.8% fat, 10.0% carbohydrate), a LC meal resulted in significantly greater postprandial GLP-1, GIP, and PYY but lower ghrelin compared to an isocaloric low fat (LF) meal after 2 weeks of eating a LF diet (10.3% fat, 75.2% carbohydrate; all p≤0.02). However, the observed differences in gut-derived appetite hormones were incommensurate with subsequent ad libitum energy intake across the day, which was 551±103 kcal (p<0.0001) greater following the LC diet as compared to the LF diet. These data suggest that other diet-related factors can dominate the effects of gut-derived appetite hormones on ad libitum energy intake, at least in the short-term.

The authors have declared no competing interest.

NCT03878108

This work was supported by the Intramural Research Program of the NIH, National Institute of Diabetes & Digestive & Kidney Diseases under award number 1ZIADK013037.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Institutional review board of the National Institute of Diabetes & Digestive & Kidney Diseases

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Deidentified individual subject data from consenting participants will be posted at https://osf.io/fjykq/

https://osf.io/fjykq/