The Influence of Macronutrients on Splanchnic and Hepatic Lymphocytes in Aging Mice

J Gerontol A Biol Sci Med Sci. 2015 Dec;70(12):1499-507. doi: 10.1093/gerona/glu196. Epub 2014 Oct 21.


There is a strong association between aging, diet, and immunity. The effects of macronutrients and energy intake on splanchnic and hepatic lymphocytes were studied in 15 month old mice. The mice were ad-libitum fed 1 of 25 diets varying in the ratios and amounts of protein, carbohydrate, and fat over their lifetime. Lymphocytes in liver, spleen, Peyers patches, mesenteric lymph nodes, and inguinal lymph nodes were evaluated using flow cytometry. Low protein intake reversed aging changes in splenic CD4 and CD8 T cells, CD4:CD8 T cell ratio, memory/effector CD4 T cells and naïve CD4 T cells. A similar influence of total caloric intake in these ad-libitum fed mice was not apparent. Protein intake also influenced hepatic NK cells and B cells, while protein to carbohydrate ratio influenced hepatic NKT cells. Hepatosteatosis was associated with increased energy and fat intake and changes in hepatic Tregs, effector/memory T, and NK cells. Hepatic NK cells were also associated with body fat, glucose tolerance, and leptin levels while hepatic Tregs were associated with hydrogen peroxide production by hepatic mitochondria. Dietary macronutrients, particularly protein, influence splanchnic lymphocytes in old age, with downstream associations with mitochondrial function, liver pathology, and obesity-related phenotype.

Keywords: Liver; Lymphocytes; Macronutrients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Dietary Carbohydrates / pharmacology*
  • Dietary Fats / pharmacology*
  • Dietary Proteins / pharmacology*
  • Female
  • Liver / immunology*
  • Lymphocytes / drug effects*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Viscera / immunology*


  • Dietary Carbohydrates
  • Dietary Fats
  • Dietary Proteins