title: The Influence of Macronutrients on Splanchnic and Hepatic Lymphocytes in Aging Mice.
abstract: 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.
authors.affiliation: Charles Perkins Centre, Ageing and Alzheimers Institute and the Centre for Education and Research on Ageing, Concord Hospital, and ANZAC Research Institute, Concord Hospital, University of Sydney, Sydney, Australia; david.lecouteur@sydney.edu.au.
authors.forename: David G
authors.initials: DG
authors.lastname: Le Couteur
authors.affiliation: Liver Immunology Group and AW Morrow Gastroenterology and Liver Centre, Centenary Institute, Royal Prince Alfred Hospital and University of Sydney, Sydney, Australia;
authors.forename: Szun S
authors.initials: SS
authors.lastname: Tay
authors.affiliation: Charles Perkins Centre, Ageing and Alzheimers Institute and the Centre for Education and Research on Ageing, Concord Hospital, and ANZAC Research Institute, Concord Hospital, University of Sydney, Sydney, Australia;
authors.forename: Samantha
authors.initials: S
authors.lastname: Solon-Biet
authors.affiliation: Liver Immunology Group and AW Morrow Gastroenterology and Liver Centre, Centenary Institute, Royal Prince Alfred Hospital and University of Sydney, Sydney, Australia;
authors.forename: Patrick
authors.initials: P
authors.lastname: Bertolino
authors.affiliation: Charles Perkins Centre, Ageing and Alzheimers Institute and the Centre for Education and Research on Ageing, Concord Hospital, and ANZAC Research Institute, Concord Hospital, University of Sydney, Sydney, Australia;
authors.forename: Aisling C
authors.initials: AC
authors.lastname: McMahon
authors.affiliation: Charles Perkins Centre, Ageing and Alzheimers Institute and the Centre for Education and Research on Ageing, Concord Hospital, and ANZAC Research Institute, Concord Hospital, University of Sydney, Sydney, Australia;
authors.forename: Victoria C
authors.initials: VC
authors.lastname: Cogger
authors.affiliation: Charles Perkins Centre.
authors.forename: Feyza
authors.initials: F
authors.lastname: Colakoglu
authors.affiliation: Charles Perkins Centre, Ageing and Alzheimers Institute and the Centre for Education and Research on Ageing, Concord Hospital, and ANZAC Research Institute, Concord Hospital, University of Sydney, Sydney, Australia;
authors.forename: Alessandra
authors.initials: A
authors.lastname: Warren
authors.affiliation: Charles Perkins Centre.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Holmes
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia;
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pichaud
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia;
authors.forename: Martin
authors.initials: M
authors.lastname: Horan
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia;
authors.forename: Carolina
authors.initials: C
authors.lastname: Correa
authors.affiliation: Institute of Biotechnology, University of Helsinki, Helsinki, Finland;
authors.forename: Richard G
authors.initials: RG
authors.lastname: Melvin
authors.affiliation: University of New South Wales, Sydney, Australia;
authors.forename: Nigel
authors.initials: N
authors.lastname: Turner
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia;
authors.forename: J William O
authors.initials: JW
authors.lastname: Ballard
authors.affiliation: EWOS Innovation, Dirdal, Norway;
authors.forename: Kari
authors.initials: K
authors.lastname: Ruohonen
authors.affiliation: Charles Perkins Centre, Faculty of Veterinary Science and School of Biological Sciences, University of Sydney, Sydney, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Raubenheimer
authors.affiliation: Charles Perkins Centre, School of Biological Sciences, University of Sydney, Sydney, Australia.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Simpson
mesh_terms: D000367:Age Factors; D000818:Animals; D004040:Dietary Carbohydrates / Q000494:pharmacology*; D004041:Dietary Fats / Q000494:pharmacology*; D004044:Dietary Proteins / Q000494:pharmacology*; D005260:Female; D008099:Liver / Q000276:immunology*; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014781:Viscera / Q000276:immunology*
chemical_list: D004040:Dietary Carbohydrates; D004041:Dietary Fats; D004044:Dietary Proteins
keywords: Liver; Lymphocytes; Macronutrients