Table 1.
Dietary patterns and their impacts on obesity development and BBB integrity
| Strain | Sex | Age or Weight |
Diet | Control Diet | Time | Methodology for BBB integrity | Phenotype and Mechanism of BBB dysfunction | Reference |
|---|---|---|---|---|---|---|---|---|
| CD-1 mice | Male | 8 w |
Fat: 60 kcal % Protein: 20 kcal % Carbohydrate: 20 kcal % (Research Diets, D12492) |
Fat: 10 kcal % Protein: 20 kcal % Carbohydrate: 70 kcal % (Research Diets, D12450J) |
16 or 36 w | Radiolabeled albumin and sucrose |
Increases 99mTc-albumin in the whole brain; Increases 14C-sucrose in hypothalamus and hippocampus; Decreases ZO-1 and Claudin-12 protein levels in whole brain lysate; Decreases ZO-1 and Occludin expression in hypothalamus. |
[72] |
| C57BL/6J mice | Female | 6 w |
Fat: 40 kcal % Protein: 12.6 kcal % Carbohydrate: 47.4 kcal % (Specialty Feeds, SF07-050) |
Fat: 9.4 kcal % Protein: 14.7 kcal % Carbohydrate: 75.9 kcal % (American Institute of Nutrition, AIN-93 M) |
10 w | Immunofluorescence staining for IgG | Increases extravasation of IgG in cortex and hippocampus | [73] |
| ICR mice | Male | 20–25 g |
Fat: 20.1 (w/w) % Protein: 18.3 (w/w) % Carbohydrate: 51.2 (w/w) % |
Fat: 5.1 (w/w) % Protein: 23.5 (w/w) % Carbohydrate: 50.3 (w/w) % |
8 w | EB staining |
Increases extravasation of EB in cortex; Disrupts the polymerization of ZO-1 and Occludin in brain. |
[74] |
| C57BL/6J mice | Female | 6 w |
Fat: 40 kcal % Protein: 12.6 kcal % Carbohydrate: 47.4 kcal % (Specialty Feeds, SF07-050) |
Fat: 9.4 kcal % Protein: 14.7 kcal % Carbohydrate: 75.9 kcal % (American Institute of Nutrition, AIN-93 M) |
9 m | Immunofluorescence staining for IgG and apoB | Increases extravasation of IgG and apoB in cortex. | [75] |
| C57BL/6J mice | Male | 12–16 w |
Fat: 15.7 (w/w) % Protein: 17.6 (w/w) % Carbohydrate: 45.7 (w/w) |
Fat: 4.5 (w/w) % Protein: 20 (w/w) % Carbohydrate: 52 (w/w) % |
8 w | TMR-conjugated dextran and EB leakage |
Increases leakage of dextran around microvessles in cortex; Increases extravasation of EB in brain. Decreases the protein levels of ZO-1, Occludin and claudin-5 in isolated brain vessels. |
[77] |
| Sprague-Dawley albino rats | Male | 60 d |
Fat: 40 kcal % Protein: 21 kcal % Carbohydrate: 38 kcal % (Harlan Teklad, TD.04489) |
Fat: 13 kcal % Protein: 29 kcal % Carbohydrate: 58 kcal % (Lab Diet, formula 5001) |
90 d | NaFI leakage |
Increases extravasation of NaFI in hippocampus; Decreases the mRNA expression of claudin-5, -12, and ZO-2 in the choroid plexus, Decreases the mRNA levels of Occludin in BBB capillaries. |
[78] |
| C57BL/6J mice | Male | 8 w |
Fat: 60 kcal % Protein: 20 kcal % Carbohydrate: 20 kcal % (Research Diets, D12492) |
Fat: 10 kcal % Protein: 20 kcal % Carbohydrate: 70 kcal % (Research Diets, D12450) |
8 w or 12 w or 16 w |
EB, NaFI and IgG leakage; TEM observation for BBB ultrastructure |
Increases extravasation of NaFI in hippocampus (12 w HFD); Increases extravasation of EB in hippocampus (16 w HFD); Increases extravasation of IgG in hippocampus (12/16 w HFD); Induces involution and atrophy of tight junctions in hippocampus (16 w HFD); Reduces the coverage of pericyte in e hippocampus (16 w HFD); Increases transcytotic vesicles in endothelial cells in hippocampus (16 w HFD). |
[79] |
| C57B6/J mice | Female | 6 w |
Fat: 45 kcal % Protein: 20 kcal % Carbohydrate: 35 kcal % (Research Diets, D12451) |
Fat: 10 kcal % Protein: 20 kcal % Carbohydrate: 70 kcal % (Research Diets, D12450B) |
until fat enough | EB and IgG leakage |
Increases extravasation of EB and IgG in the ARC of neonatal offspring; Increases fenestrations in endothelial cells in the ARC of neonatal offspring; Increases the mRNA levels of claudin-1, -3 and ZO-1 in the ARC of neonatal offspring; Increases active transcellular transport in the ARC of neonatal offspring . |
[82] |
| C57BL/6J mice | Male | 7 w |
Fat: 60 kcal % (SYSE, PD6001) |
Fat: 10 kcal % (SYSE, D12450J) |
4 m | mRNA level of TJs | Decreases the mRNA levels of ZO-1 and Occludin in hippocampus and prefrontal cortex. | [83] |
| C57BL/6J mice | Male | 6 w |
Fat: 45 kcal % (Research Diets) |
Fat: 17 kcal % (Mucedola Srl) |
19 w | Albumin leakage |
Increases the number of scattered albumin-positive neurons (extravasated albumin is taken up by neuronal cells) in hippocampus; Decreases the transcription of tight junction protein 1, Occludin and Claudin5. |
[84] |
| C57BL/6J mice | Male | 2 m |
Fat: 45 kcal % Protein: 20 kcal % Carbohydrate: 35 kcal % (D12451) |
Fat: 13.5 kcal % Protein: 28.5 kcal % Carbohydrate: 58 kcal % (Purina 5001) |
2 m | Comparative proteomic |
Downregulates 47 proteins in the cerebral microvessels, including cytoskeletal proteins, chaperons, enzymes, transport-related proteins, and regulators for transcriptional and translational activities; Upregulates two proteins, involved in mRNA transport and processing. |
[76] |
| C57BL6/J mice | Male | 6 w |
Fat: 29.9 (w/w) % Protein: 13.6 (w/w) % Crude Fibre: 4.7 (w/w) % (Specialty Feeds, SF14-088) |
Fat: 4 (w/w) % Protein: 13.6 (w/w) % Crude Fibre: 4.7 (w/w) % (Specialty Feeds, AIN-93 M) |
4 or 24 w | IgG leakage | Increases extravasation of IgG in cortex and hippocampus. | [125] |
| Sprague-Dawley albino rats | Male | 250–275 g |
Fat: 40 kcal % Protein: 21 kcal % Carbohydrate: 38 kcal % (Harlan Teklad, TD.04489) |
Fat: 13 kcal % Protein: 29 kcal % Carbohydrate: 58 kcal % (Lab Diet, formula 5001) |
until fat enough | NaFI leakage | Increases extravasation of NaFI in hippocampus and cortex. | [149] |
| Fischer rats | Female | 6 m |
Hydrogenated coconut oil: 10 (w/w) % Cholesterol: 2 (w/w) % (MP Biomedicals, ‘Custom Diet D2-AIN93 without choline bitartrate and with 2% cholesterol’) |
Fat: 13 kcal% Protein: 34 kcal% Carbohydrate: 53 kcal% (Harlan Teklad, 8656) |
6 m |
SMI-71 (an antibody specific to the rat endothelial-barrier protein) |
Decreases the immunoreactivity of SMI-71in cortex and hippocampus; Increases the protein levels of Occludin in hippocampus. |
[148] |
| C57BL/6 N mice | Male | 8 w |
Fat: 60 kcal % Protein: 19 kcal % Carbohydrate: 21 kcal % (Ssniff, D12492) (for acute HFD) |
Fat: 9 kcal % Protein: 34 kcal % Carbohydrate: 57 kcal % (Ssniff, V1554) |
3 d-4 w | mRNA levels of transporters |
Decreases the mRNA levels of Glut-1 after 3 d HFD, until 1 w HFD. Decreases the immunoreactivity of Glut-1 after 3–7 d HFD. The expression of Glut-1 is restored after 4 w HFD and the serum levels of VEGF increases. |
[95] |
| C57BL/6 mice | Male | 8 w |
Fat: 59 kcal % Protein: 18 kcal % Carbohydrate: 23 kcal % (Test Diet, 58G9) |
Fat: 12 kcal % Protein: 18 kcal % Carbohydrate: 70 kcal % (Test Diet, 58G7) |
3 d | Protein levels of transporters | Decreases the expression and function of Glut-1. | [96] |
| C57BL/6 N mice | Male | 8 w |
Fat: 56.7 kcal % Protein: 20 kcal % Carbohydrate: 23.1 kcal % (CLEA, HFD32) |
Fat: 12 kcal % Protein: 29 kcal % Carbohydrate: 59 kcal % (CLEA, CE-2) |
2 or 10 w | EB leakage; Transporter and receptor expression analyze |
2 w HFD: Does not induce the extravasation of EB; Decreases the expression of Claudin-5, Occludin and ZO-1; Decreases the expression of Mdra1, Glut-1, P-gp, LAT1, Mct1, TfR and Lrp1 in the brain capillary; 10 w HFD: Increases the expression of Mdra1, Glut-1, P-gp, LAT1, Mct1 and TfR in the brain capillary; Increases the expression of Claudin-5, Occludin and ZO-1. |
[97] |
| Mongrel dog | Male | 27–40 kg |
Fat: 80 kcal % (Harlan Teklad) |
Fat: 17 kcal % (Harlan Teklad) |
7 w | Marked intravenous insulin injection | Decreases the CNS insulin level. | [100] |
| CD-1 mice | Male | 8–10 w or 56–64 w | Not mentioned | Not mentioned | Not mentioned | Intravenous radiolabeled insulin injection; Transcardiac radiolabeled insulin brain perfusion |
Decreases the transport of insulin across the BBB; Regulates the BBB transport by circulating factors such as the triglyceride triolein (increases the brain uptake of insulin). |
[101] |
| Sprague Dawley rats | Male | 8 w |
Fat: 60 kcal % Protein: 20 kcal % Carbohydrate: 20 kcal % (Research Diets, D12492) |
Normal chow diet (No details) |
4 w | Radiolabeled insulin uptake and degradation tests |
Decreases isolated-BECs insulin uptake; Increases NF-κB binding activity. |
[102] |
| C57BL/6NHsd mice | Male | 6 w |
Fat: 40 kcal % Protein: 16 kcal % Carbohydrate: 44 kcal % (Test Diet, 5TJN) Sugar: 42 g/L, add to the water |
Fat: 18 kcal % Protein: 24 kcal % Carbohydrate: 58 kcal % (Harlan Teklad, 2018) |
14 w | Intraperitoneal glucose injection; Glucose and insulin tolerance tests |
Reduces brain insulin resistance by decreasing tyrosine phosphorylation of insulin receptor and increasing serine phosphorylation of IRS-1; Induces inflammatory (NF-κB, JNK) and stress responses (p38 MAPK, CHOP). |
[104] |
| Lean FA/FA rats or genetically obese Zucker fa/fa rats | Male | 9 w |
For lean FA/FA rats: Fat: 40 (w/w) % (Harlan Teklad, TD-97,113) |
For lean FA/FA rats: Fat: 4.50 (w/w) % (Lab Diet, 5001) |
For lean FA/FA rats: 10 w |
Intravenous radiolabeled leptin injection |
Decreases the permeability of leptin at the BBB; Induces the saturation of leptin receptor at the BBB. |
[108] |
| Suffolk × Greyface crossbreeds sheep | Male | 1 y | Comprising 50% chopped hay, 30% rolled barley and 9% soyabean meal, etc.: ad libitum for 40 w; then restricted to 0.75 × maintenance for 16 w |
Comprising 50% chopped hay, 30% rolled barley and 9% soyabean meal, etc.: restricted to 1.1 × maintenance for 40 w; then ad libitum for 16w |
56 w | i.c.v. injection of marked leptin | Decreases the transport of leptin across the BBB. | [109] |
| C57BL/6 and AKR mice | Male | 4 w |
Fat: 45 kcal % Protein: 20 kcal % Carbohydrate: 35 kcal % (Research Diets, D12451) |
Fat: 10 kcal % Protein: 20 kcal % Carbohydrate: 70 kcal % (Research Diets, D12450) |
56d | Intra-cerebroventricular and peripheral leptin injection | Induces resistance to peripherally administered leptin, while retaining sensitivity to centrally administered leptin. | [111] |