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Cited by 220Regulation of Appetite and ObesityNutrition, Health and Food BehaviorDiet, Metabolism, and Disease

Protein‐leverage in Mice: The Geometry of Macronutrient Balancing and Consequences for Fat Deposition

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Sørensen, Allan, Mayntz, David, Raubenheimer, David, Simpson, Stephen J.·2008·Obesity
DOI 10.1038/oby.2007.58
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Abstract

Objective: The Protein‐Leverage Hypothesis proposes that humans regulate their intake of macronutrients and that protein intake is prioritized over fat and carbohydrate intake, causing excess energy ingestion when diets contain low %protein. Here we test in a model animal, the mouse: (i) the extent to which intakes of protein and carbohydrate are regulated; (ii) if protein intake has priority over carbohydrates so that unbalanced foods low in %protein leads to increased energy intake; and (iii) how such variations in energy intake are converted into growth and storage. Methods and Procedures: We fed mice one of five isocaloric foods having different protein to carbohydrate composition, or a combination of two of these foods (N = 15). Nutrient intake and corresponding growth in lean body mass and lipid mass were measured. Data were analyzed using a geometric approach for analyzing intake of multiple nutrients. Results: (i) Mice fed different combinations of complementary foods regulated their intake of protein and carbohydrate toward a relatively well‐defined intake target. (ii) When mice were offered diets with fixed protein to carbohydrate ratio, they regulated the intake of protein more strongly than carbohydrate. This protein‐leverage resulted in higher energy consumption when diets had lower %protein and led to increased lipid storage in mice fed the diet containing the lowest %protein. Discussion: Although the protein‐leverage in mice was less than what has been proposed for humans, energy intakes were clearly higher on diets containing low %protein. This result indicates that tight protein regulation can be responsible for excess energy ingestion and higher fat deposition when the diet contains low %protein.

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  • During amino acid restriction, mammals increase their consumption of diets low in protein to acquire sufficient protein to satisfy organismal requirements, despite increasing their overall caloric intake.

    “During amino acid restriction, mammals increase their consumption of diets low in protein to acquire sufficient protein to satisfy organismal requirements, despite increasing their overall caloric intake125–129.”

    From Metabolic messengers: FGF21 (2021) · cites this paper as [126]

  • Studies using the geometric framework generally observe either a very weak or nonexistent regulation of fat intake, and fat acts to dilute protein and carbohydrate and thus increase intake.

    “the studies using the geometric framework generally observe either a very weak or nonexistent regulation of fat intake, and as a result, fat acts to dilute protein and carbohydrate and thus increase intake”

    From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [29]

  • Several studies using the geometric framework suggest that animals eat to a carbohydrate target.

    “several studies suggest that animals eat to a carbohydrate target”

    From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [29]

  • Protein is prioritized and regulated to a specific target, so small changes in the proportion of dietary protein can induce large changes in total food and energy intake (protein leveraging).

    “The observation that protein is prioritized and regulated to a specific target suggests that small changes in the proportion of dietary protein can induce large changes in total food and energy intake, a concept termed protein leveraging”

    From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [29]

  • Nutritional geometry studies strongly argue that a number of species defend protein intake, eat to a protein target, and prioritize protein over fat or carbohydrate intake.

    “These data strongly argue that a number of species defend protein intake, eat to a protein target, and prioritize protein over fat or carbohydrate intake”

    From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [29]

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Research works printed but not linked: 2

  1. Taconic. Products and service catalogue (European edition). 2007.
  2. Simpson SJ, Raubenheimer D. A multilevel analysis of feeding-behavior- the geometry of nutritional decisions. Philos Trans R Soc Lond B Biol Sci 1993;342:381-402.

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Authors
Sørensen, A., Mayntz, D., Raubenheimer, D., & Simpson, S. J.
Affiliations
  • Aarhus University (DK)
  • University of Auckland (NZ)
  • The University of Sydney (AU)
Corresponding author
Raubenheimer, David
ORCID
Venue
Obesity
Publisher
Wiley
Published
2008-03
Volume
16
Issue
3
Pages
566-571
ISSN
  • 1930-7381 (ISSN-L)
  • 1930-739X
DOI
10.1038/oby.2007.58
OpenAlex
W1986307596
Cited by
218
References
37
Citations by year
2026: 9 · 2025: 13 · 2024: 15 · 2023: 12 · 2022: 8 · 2021: 14 · 2020: 15 · 2019: 15 · 2018: 10 · 2017: 18 · 2016: 11 · 2015: 14 · 2014: 13 · 2013: 9 · 2012: 20
FWCI
3.12
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 1650 d)
Locations
  • Obesity (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Nursing › Nutrition and Dietetics › Nutrition, Health and Food Behavior
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
Keywords
protein intake, carbohydrate intake, energy intake, fat deposition, lean body mass
MeSH terms
Adipose Tissue, Animals, Animal Nutritional Physiological Phenomena, Appetite Regulation, Behavior, Animal, Body Composition, Energy Intake, Dietary Carbohydrates, Dietary Proteins, Food Preferences, Male, Time Factors, Micronutrients, Models, Animal, Lipid Metabolism, Mice

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