Low-protein diets with fixed carbohydrate content promote hyperphagia and sympathetically mediated increase in energy expenditure
Abstract
SCOPE: Dietary protein restriction elicits hyperphagia and increases energy expenditure; however, less is known of whether these responses are a consequence of increasing carbohydrate content. The effects of protein-diluted diets with fixed carbohydrate content on energy balance, hormones, and key markers of protein sensing and thermogenesis in tissues are determined. METHODS AND RESULTS: Obesity-prone rats (n = 13-16 per group) are randomized to diets containing fixed carbohydrate (52% calories) and varying protein concentrations: 15% (control), 10% (mild protein restriction), 5% (moderate protein restriction) or 1% (severe protein restriction) protein calories, or protein-matched to 5% protein, for 21 days. Propranolol and ondansetron are administered to interrogate the roles of sympathetic and serotonergic systems, respectively, in diet-induced changes in energy expenditure. It is found that mild-to-moderate protein restriction promotes transient hyperphagia, whereas severe protein restriction induces hypophagia, with alterations in meal patterns. Protein restriction enhances energy expenditure that is partly attenuated by propranolol, but not ondansetron. Moderate to severe protein restriction decreases gains in body weight, lean and fat mass, decreased postprandial glucose and leptin, but increased fibroblast growth factor-21 concentrations. Protein-matching retains lean mass suggesting that intake of dietary protein, but not calories, is important for preserving lean mass. Notably, protein restriction increases the protein and/or transcript abundance of key amino acid sensing molecules in liver and intestine (PERK, eIF2α, ATF2, CHOP, 4EBP1, FGF21), and upregulated thermogenic markers (β2AR, Klotho, HADH, UCP-1) in brown adipose tissue. CONCLUSION: Low-protein diets promote hyperphagia and sympathetically mediated increase in energy expenditure, prevent gains in tissue reserves, and concurrently upregulate hepatic and intestinal amino acid sensing intermediaries and thermogenic markers in brown adipose tissue.
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Low-protein diets induce hyperphagia, particularly in rodent models.
“a number of studies demonstrate that low-protein diets induce hyperphagia, particularly in rodent models”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [79]
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- Authors
- Zapata, R. C., Singh, A., Pezeshki, A., Avirineni, B. S., Patra, S., & Chelikani, P. K.
- Affiliations
- University of Calgary (CA)
- Oklahoma State University (US)
- Corresponding author
- Chelikani, Prasanth K.
- Venue
- Molecular Nutrition & Food Research
- Publisher
- Wiley
- Published
- 2019-08-07
- Volume
- 63
- Issue
- 21
- Pages
- e1900088-e1900088
- ISSN
- 1613-4125 (ISSN-L)
- 1613-4133
- OpenAlex
- W2966081695
- Cited by
- 33
- References
- 49
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 7 · 2023: 6 · 2022: 4 · 2021: 4 · 2020: 2
- FWCI
- 1.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Nutrition & Food Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canada Foundation for Innovation
- Ministry of Advanced Education, Government of Alberta
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- low-protein diet, protein restriction, hyperphagia, energy expenditure, sympathetic nervous system, serotonergic system, obesity-prone rats, FGF21, amino acid sensing, PERK-eIF2α pathway, brown adipose tissue thermogenesis, leptin, postprandial blood glucose, lean body mass, body composition, propranolol, ondansetron
- MeSH terms
- Animals, Body Composition, Body Weight, Adipose Tissue, Brown, Energy Intake, Dietary Carbohydrates, Energy Metabolism, Fibroblast Growth Factors, Hyperphagia, Liver, Male, Rats, Sprague-Dawley, Diet, Protein-Restricted, Leptin, Thermogenesis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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