PXD047177

PXD047177 is an original dataset announced via ProteomeXchange.

Title	Protein-restricted diet increases circulating FGF21 levels and necessitating an increase in energy intake to maintain body weight in healthy human individuals
Description	Dietary protein restriction has been shown to increase energy expenditure and to improve insulin sensitivity in mice, but it is unknown whether humans exhibit similar phenotype to a prolonged eucaloric protein-restricted diet that meet daily protein minimum requirements. We hypothesize that a protein-restricted diet would necessitate an increase in energy intake in order to maintain body weight in healthy, lean men. We designed an overall amino acid diluted diet meeting the requirement for daily protein intake and essential amino acids. Healthy, young, lean men adhered to a protein-restricted, high-carbohydrate diet (LPHC: protein 9E%, 70E% carbohydrate, and 21E% fat) or a protein-restricted, high-fat diet (LPHF: 9E% protein, 50E% fat, and 40E% carbohydrate) for 5 weeks, followed by another 5 weeks on a higher, standard protein diet (HPD: 18E% protein), reflecting their habitual diet. The diets were eucaloric, and energy provision was adjusted to maintain body weight throughout the interventions. In addition, wild type (WT), and FGF21 knockout mice were also fed LPHC, LPHF diets, or a standard higher diet (HPD) for a total of 10 weeks. Our results showed that prolonged eucaloric LPHC and LPHF diets necessitated a daily increase of 20-21% (2.5 MJ) in food intake to maintain body weight compared to pre-intervention in healthy, lean men. Additionally, fasting plasma FGF21 levels increased from 90±125 pg/ml and 78±34 pg/ml to 257±99 pg/ml and 160±52 pg/ml at the end of the LPHC and LPHF, respectively. Furthermore, proteomic analysis revealed adaptations in the respiratory chain in human adipose tissue after 5-week protein-restricted diets. This was found to be dependent on FGF21 in mice, indicating increased energy utilization through alternative UCP1-independent futile cycle pathways likely mediated by FGF21. Moreover, whole-body insulin sensitivity, measured by a hyperinsulinemic-euglycemic clamp, was increased by 16% after the LPHC intervention while maintained after the LPHF intervention, despite the high fat intake. These findings suggest that a protein-restricted diet could serve as a promising approach to prevent weight gain and comorbidities associated with obesity.
HostingRepository	PRIDE
AnnounceDate	2025-04-22
AnnouncementXML	Submission_2025-04-22_03:57:59.077.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Natalie Krahmer
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-11-22 12:03:48	ID requested
⏵ 1	2025-04-22 03:57:59	announced

10.1038/s42255-025-01236-7;

Nicolaisen TS, Lyster AE, Sj, ø, berg KA, Haas DT, Voldstedlund CT, Lundsgaard AM, Jensen JK, Madsen EM, Nielsen CK, Bloch-Ibenfeldt M, Wewer Albrechtsen NJ, Rose AJ, Krahmer N, Clemmensen C, Richter EA, Fritzen AM, Kiens B, Dietary protein restriction elevates FGF21 levels and energy requirements to maintain body weight in lean men. Nat Metab, 7(3):602-616(2025) [pubmed]

submitter keyword: human, energy intake, body weight, healthy,FGF21

Bente Kiens
contact affiliation	Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
contact email	bkiens@nexs.ku.dk
lab head
Natalie Krahmer
contact affiliation	Helmholtz Center Munich
contact email	natalie.krahmer@helmholtz-muenchen.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD047177
     1. Label: PRIDE project
     2. Name: Protein-restricted diet increases circulating FGF21 levels and necessitating an increase in energy intake to maintain body weight in healthy human individuals