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  • Review Article
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Programming of metabolism by adipokines during development

Nature Reviews Endocrinology volume 19, pages 385–397 (2023)Cite this article

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Abstract

The intrauterine and early postnatal periods represent key developmental stages in which an organism is highly susceptible to being permanently influenced by maternal factors and nutritional status. Strong evidence indicates that either undernutrition or overnutrition during development can predispose individuals to disease later in life, especially type 2 diabetes mellitus and obesity, a concept known as metabolic programming. Adipose tissue produces important signalling molecules that control energy and glucose homeostasis, including leptin and adiponectin. In addition to their well-characterized metabolic effects in adults, adipokines have been associated with metabolic programming by affecting different aspects of development. Therefore, alterations in the secretion or signalling of adipokines, caused by nutritional insults in early life, might lead to metabolic diseases in adulthood. This Review summarizes and discusses the potential role of several adipokines in inducing metabolic programming through their effects during development. The identification of the endocrine factors that act in early life to permanently influence metabolism represents a key step in understanding the mechanisms behind metabolic programming. Thus, future strategies aiming to prevent and treat these metabolic diseases can be designed, taking into consideration the relationship between adipokines and the developmental origins of health and disease.

Key points

  • Undernutrition or overnutrition during critical developmental periods can alter the predisposition to metabolic diseases later in life, including type 2 diabetes mellitus and obesity, a concept known as metabolic programming.

  • Leptin and adiponectin are produced by adipocytes and in addition to their well-characterized metabolic effects in adults, these adipokines have been associated with metabolic programming by affecting different developmental aspects.

  • Maternal obesity, gestational diabetes mellitus and other metabolic imbalances during pregnancy affect the maternal circulating levels of leptin and adiponectin and the fetal exposure to these adipokines.

  • Early infancy represents a critical developmental period in which nutritional insults, associated with the action of adipokines, determine the risk of metabolic diseases later in life.

  • Leptin action in early life possibly programmes metabolism by controlling the development of hypothalamic neurocircuits, inducing permanent changes in the preference for hyper-palatable foods and decreasing energy expenditure.

  • Adiponectin effects in the mother and placenta regulate fetal exposure to nutrients and consequently fetal growth and/or nutrition, with long-term consequences for metabolism and predisposition to diseases.

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Fig. 1: Environmental factors that potentially programme an organism to be more or less susceptible to disease in adulthood.
Fig. 2: Key milestones in the effects of leptin during the postnatal period in mice.
Fig. 3: Proposed mechanisms to explain the developmental effects of adiponectin.

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Acknowledgements

J.D. acknowledges the support of the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP-Brazil; grant number: 2020/01318–8). J.D. also thanks M. Metzger (University of São Paulo) and F. Wasinski (Federal University of São Paulo) for critical reading of the manuscript.

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    Jose Donato Jr

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Donato, J. Programming of metabolism by adipokines during development. Nat Rev Endocrinol 19, 385–397 (2023). https://doi.org/10.1038/s41574-023-00828-1

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