Contribution of macronutrients to obesity: implications for precision nutrition



The specific metabolic contribution of consuming different energy-yielding macronutrients (namely, carbohydrates, protein and lipids) to obesity is a matter of active debate. In this Review, we summarize the current research concerning associations between the intake of different macronutrients and weight gain and adiposity. We discuss insights into possible differential mechanistic pathways where macronutrients might act on either appetite or adipogenesis to cause weight gain. We also explore the role of dietary macronutrient distribution on thermogenesis or energy expenditure for weight loss and maintenance. On the basis of the data discussed, we describe a novel way to manage excessive body weight; namely, prescribing personalized diets with different macronutrient compositions according to the individual’s genotype and/or enterotype. In this context, the interplay of macronutrient consumption with obesity incidence involves mechanisms that affect appetite, thermogenesis and metabolism, and the outcomes of these mechanisms are altered by an individual’s genotype and microbiota. Indeed, the interactions of the genetic make-up and/or microbiota features of a person with specific macronutrient intakes or dietary pattern consumption help to explain individualized responses to macronutrients and food patterns, which might represent key factors for comprehensive precision nutrition recommendations and personalized obesity management.

Key points

  • Body weight and adiposity rely on energy equilibrium driven by energy-yielding macronutrient intake and energy expenditure under strict neuroendocrine control.

  • Complex energy homeostasis interactions between carbohydrates, lipids and proteins (dietary quantity and quality) follow the interpretation of their separate roles on fuel metabolism.

  • The intake of simple sugars and some saturated fatty acids has adverse effects on body adiposity, while protein and fibre consumption seem to beneficially modulate satiety and energy metabolism-related processes.

  • Personal genetic background and gut microbiota features contribute to explaining some metabolic inter-individual differences to macronutrient consumption.

  • Advances in understanding metabolism pathways and hormonal control depending on macronutrient intake involved in energy utilization are needed for precision and public health nutrition.

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Fig. 1: Key metabolic mechanisms on body weight regulation.


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R.S.-C. acknowledges financial support from the Juan de la Cierva Programme — Training Grants of the Spanish State Research Agency of the Spanish Ministerio de Ciencia e Innovación y Ministerio de Universidades (FJC2018-038168-I). R.S.-C., S.N.-C. and J.A.M. were part of the EU project Food4Me supported by the European Commission under the Food, Agriculture, Fisheries and Biotechnology Theme of the 7th Framework Programme for Research and Technological Development (ID no. 265494). M.A.M.-G. acknowledges the support of the European Research Council, Advanced Research Grant, PREDIMED-PLUS (ERC-2013-ADG #340918).

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Supplementary information


Ileal brake

The delay in gastric emptying and small intestinal transit induced by the presence of certain nutrient solutions or products in the ileum.

Weende approach

The calculation of carbohydrate from the known content of fat, protein and fibre of a food.


The science that identifies and characterizes gene variants associated with differential response to nutrients and relates this variation to diverse disease states.


Encompasses life-course environmental exposures (including lifestyle factors) from the prenatal period onwards, including the body’s response through different endogenous metabolic processes.

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San-Cristobal, R., Navas-Carretero, S., Martínez-González, M. et al. Contribution of macronutrients to obesity: implications for precision nutrition. Nat Rev Endocrinol 16, 305–320 (2020).

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