Early-life sodium deprivation programs long-term changes in ingestive behaviors and energy expenditure in C57BL/6J

Alisha A Ziegler1,2, Samuel B R Lawton1, Connie C Grobe2

  • 1Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.

Insights

Early-life sodium restriction in mice led to lasting changes in metabolism and feeding behaviors. These programmed effects persisted into adulthood, impacting growth and energy expenditure.

Area of Science:

  • Physiology
  • Developmental Biology
  • Nutritional Science

Background:

  • Postnatal growth failure is a major issue for premature infants.
  • Sodium (Na) homeostasis is crucial for optimal growth, especially in early life.
  • Early-life sodium dysregulation may contribute to growth restriction and later cardiometabolic disease.

Purpose of the Study:

  • To investigate the effects of prolonged versus early-life sodium depletion on growth, body composition, intake behaviors, and energy expenditure in mice.
  • To determine if early-life sodium restriction programs long-term changes in metabolic and autonomic functions.

Main Methods:

  • Two studies using C57BL/6J mice were conducted.
  • Study 1: Mice received low (0.04%) or normal/high (0.30%) sodium diets from 3 to 18 weeks of age.
  • Study 2: Mice received low (0.04%) or normal/high (0.30%) sodium diets from 3 to 6 weeks, then a standard (0.15%) sodium diet until 18 weeks. Ingestive behaviors, body composition, and energy expenditure were monitored. Hexamethonium was administered to assess autonomic function.

Main Results:

  • Prolonged sodium restriction caused delayed growth and elevated basal metabolic rate.
  • Early-life sodium restriction led to temporary growth delays that resolved upon return to a standard diet.
  • Previously restricted mice showed sustained changes in feeding behavior, reduced food intake, increased water intake, and higher aerobic energy expenditure from 6 to 18 weeks.
  • Hexamethonium abolished the elevated basal metabolic rate in previously restricted mice, indicating autonomic involvement.

Conclusions:

  • Early-life sodium restriction can program persistent changes in ingestive behaviors, autonomic function, and energy expenditure.
  • These programmed changes continue into adulthood, suggesting a link between early nutrition and long-term health.
  • Findings highlight the critical role of early-life sodium balance in development and metabolic programming.

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