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Review
. 2025 Feb;47(2):e2400071.
doi: 10.1002/bies.202400071. Epub 2024 Nov 6.

Macronutrient interactions and models of obesity: Insights from nutritional geometry

Jibran A Wali  1   2 , Duan Ni  1   3 , David Raubenheimer  1   2 , Stephen J Simpson  1   2
Affiliations
Review

Macronutrient interactions and models of obesity: Insights from nutritional geometry

Jibran A Wali et al. Bioessays. 2025 Feb.

Abstract

The global obesity epidemic results from a complex interplay of genetic and environmental factors, with diet being a prominent modifiable element driving weight gain and adiposity. Although excess intake of energetic macronutrients is implicated in causing obesity, ongoing debate centers on whether sugar or fat or both are driving the rising obesity rates. This has led to competing models of obesity such as the "Carbohydrate Insulin Model", the "Energy Balance Model", and the "Fructose Survival Hypothesis". Conflicting evidence from studies designed to focus on individual energetic macronutrients or energy rather than macronutrient mixtures underlies this disagreement. Recent research in humans and animals employing the nutritional geometry framework (NGF) emphasizes the importance of considering interactions among dietary components. Protein interacts with carbohydrates, fats, and dietary energy density to influence both calorie intake ("protein leverage") and, directly and indirectly, metabolic physiology and adiposity. Consideration of these interactions can help to reconcile different models of obesity, and potentially cast new light on obesity interventions.

Keywords: macronutrient; nutritional geometry; obesity.

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References

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