TABLE 1.
Effects of obesity and MetS on the immune system1
| Immune system parameter | Model/condition | Effect on immune system | Reference |
| Bone marrow characteristics | Obese men and women | Bone marrow adiposity | (39) |
| Wistar rats fed HFD | ↑ Proinflammatory gene expression of bone marrow MSCs | (40) | |
| Thymus characteristics | C56BL/6 mice fed HFD | ↑ Thymic involution and adiposity | (18) |
| Diabetic rats, streptozotocin-induced | ↑ Thymic involution | (41) | |
| Diabetic mice, alloxan-induced | ↑ Thymic involution | (42) | |
| Leptin deficiency (ob/ob mice) | ↓ Thymus size and cellularity, ↑ thymocyte apoptosis | (43) | |
| Spleen characteristics | C56BL/6 mice fed HFD | ↑ Effector/memory T cell, ↓ TCR diversity | (18) |
| Lymph node characteristics | Diet-induced obese mice | ↓ Inguinal lymph node size, ↓ T cell numbers | (44) |
| Impaired lymphatic fluid transport, DC migration | (44) | ||
| Leukocyte development | Adipocyte-rich BM in C57BL/6J mice | ↓ Hematopoeisis | (45) |
| Leptin receptor deficiency (db/db mice) | ↓ Hematopoeisis | (46) | |
| Low HDL, Abca1−/− Abcg1−/− BM mice | ↓ BM HSC and myeloid progenitor proliferation | (47) | |
| C56BL/6 mice fed HFD | ↑ Myeloid progenitor cells, ↓ lymphoid progenitors | (18) | |
| ↓ Thymic output of naïve T cells | (18) | ||
| Obese and insulin resistant patients | ↓ Thymic output of naïve T cells | (18) | |
| Clinical leukocyte profiles | MetS populations | ↑ WBC counts | (48–50) |
| Healthy men, MELANY cohort | ↑ 7.6% T2DM risk for every 1000 cells/mm3 increase in WBCs | (51) | |
| Weight loss, overweight, and obese subjects | ↓ WBC counts | (52) | |
| Leukocyte inflammation | Obese mouse models | ↑ M1 macrophages, ↓ M2 macrophages in adipose | (53–55) |
| ↑ T cell infiltration in adipose | (13) | ||
| ↑ TH1 cells, ↓ Treg cells in adipose | (13, 20) | ||
| Obese human subjects | ↑CD4+ T cells, ↓ CD8+ peripheral T cells | (56) | |
| ↑ NF-κB activation in PBMCs | (19) | ||
| ↑ MIF, IL-6, TNF-α, MMP-9 mRNA expression in PBMCs | (19) | ||
| Morbidly obese human subjects | ↑ Peripheral TH2 and Treg cells | (57) | |
| ↑ CD4+ and CD8+ T cell proliferation | (57) | ||
| Weight loss, obese women | ↓ PBMC proinflammatory gene expression | (58) | |
| Weight loss, obese women | ↔ CD4+ and CD8+ ratios | (59) | |
| −/− mice | ↑ T cell lipid rafts and proliferation | (60) | |
| Pathogen defense | HDL infusion in C57BL6/CBA mice | ↑ Survival from lethal dose of LPS | (61) |
| Lipoprotein-bound LPS, septic patients | ↓ LPS bioactivity | (62) | |
| HFD-fed and ob/ob mice | ↑ Mortality from S. aureus-induced sepsis | (63) | |
| Diabetic tuberculosis patients | ↑ CD4+ TH1 and TH17 cytokines in plasma | (64) | |
| Adiponectin-deficient mice | ↑ Risk of sepsis-related mortality | (65) | |
| Immunity | Leptin deficiency (ob/ob mice) | ↓ Cell-mediated immunity | (66) |
| Diet-induced obese mice | ↓ DC antigen presentation | (67) | |
| Type 2 diabetic patients | ↓ Phagocytic activity of PBMCs | (68) | |
| Obese and diabetic mice | ↑ Lung cancer metastasis, ↓ NK cell function at early cancer stages | (69) | |
| Diet-induced obese mice | ↓ Maintenance of influenza-specific CD8+ memory T cells | (37) | |
| Obese, glucose intolerant rats | ↓ Immunological memory after hepatitis B vaccine | (70) | |
| Type 2 diabetic hemodialysis patients | ↑ Risk of hepatitis B vaccine failure | (71) | |
| Overweight children | ↑ Risk of tetanus vaccine failure | (72) | |
| Obese human subjects | ↑ Risk of influenza vaccine failure | (17) | |
| Diabetic patients | ↑ Risk of influenza-related complications and hospitalizations | (73, 74) | |
| Communities with high obesity prevalence | ↑ Risk of influenza-related hospitalizations | (74) | |
| Child obesity, NHANES 2005–2006 | ↑ Allergic disease | (75) |
1
Abca1−/− , ATP-binding cassette transporter A1; Abcg1−/− , ATP-binding cassette transporter G1; BM, bone marrow; DC, dendritic cell; HFD, high-fat diet; HSC, hematopoietic stem cell; MELANY, Metabolic, Life-Style and Nutrition Assessment in Young Adults; MetS, metabolic syndrome; MIF, migration inhibition factor; MMP-9, matrix metalloproteinase 9; MSC, mesenchymal stem cell; NK, natural killer; PBMC, peripheral blood mononuclear cell; T2DM, type 2 diabetes mellitus; TCR, T cell receptor; TH1, TH2, and TH17, T helper cells 1, 2, and 17, respectively; Treg, regulatory T; WBC, white blood cell; ↑, increase; ↓ decrease; ↔, no change.