Obesity: the protein leverage hypothesis
Abstract
Summary: The obesity epidemic is among the greatest public health challenges facing the modern world. Regarding dietary causes, most emphasis has been on changing patterns of fat and carbohydrate consumption. In contrast, the role of protein has largely been ignored, because (i) it typically comprises only ∼15% of dietary energy, and (ii) protein intake has remained near constant within and across populations throughout the development of the obesity epidemic. We show that, paradoxically, these are precisely the two conditions that potentially provide protein with the leverage both to drive the obesity epidemic through its effects on food intake, and perhaps to assuage it. We formalize this hypothesis in a mathematical model. Some supporting epidemiological, experimental and animal data are presented, and predictions are made for future testing.
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The protein leverage hypothesis could partially explain the higher energy intake observed with the ultra-processed diet.
“suggests that the protein leverage hypothesis could partially explain the increase in energy intake with the ultra-processed diet”
From Ultra-Processed Diets Cause Excess Calorie Intake and Weight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum Food Intake (2019) · cites this paper as Simpson and Raubenheimer, 2005
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 [125]
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 [105]
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- Authors
- Simpson, S. J., & Raubenheimer, D.
- Affiliations
- The University of Sydney (AU)
- University of Auckland (NZ)
- Corresponding author
- Simpson, S. J.
- Raubenheimer, D.
- Venue
- Obesity Reviews
- Publisher
- Wiley
- Published
- 2005-04-18
- Volume
- 6
- Issue
- 2
- Pages
- 133-142
- ISSN
- 1467-7881 (ISSN-L)
- 1467-789X
- OpenAlex
- W2169139775
- Cited by
- 591
- References
- 49
- Citations by year
- 2026: 15 · 2025: 31 · 2024: 30 · 2023: 36 · 2022: 28 · 2021: 53 · 2020: 39 · 2019: 34 · 2018: 82 · 2017: 41 · 2016: 28 · 2015: 25 · 2014: 24 · 2013: 20 · 2012: 25
- FWCI
- 0.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Obesity Reviews (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wissenschaftskolleg zu Berlin
- Biotechnology and Biological Sciences Research Council
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Obesity, Physical Activity, Diet
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- obesity, dietary protein, food intake regulation, energy balance, dietary fat and carbohydrates, obesity prevention
- MeSH terms
- Animals, Body Weight, Energy Intake, Dietary Proteins, Energy Metabolism, Gluconeogenesis, Humans, Liver, Models, Biological, Obesity
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