Immune-Deficient Pfp/Rag2−/− Mice Featured Higher Adipose Tissue Mass and Liver Lipid Accumulation with Growing Age than Wildtype C57BL/6N Mice
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animal Experiments
2.2. Cell Culture Experiments
2.3. Serum Analysis
2.4. Histology
2.5. Immunofluorescence
2.6. Gene Expression Analyses
2.7. Adipokine Profiling
2.8. Statistics
3. Results
3.1. The Age-Related Increase in Body Weight Coincided with a Disproportionate Increase in Adipose Tissue in Immune-Deficient, but Not Wildtype Mice
3.2. The Age-Related Increase of Visceral Adipose Tissue Mass in Immune-Deficient Mice Was Likely Attributable to Hyperplasia
3.3. Adipose Tissue Hypertrophy and Hyperplasia, Respectively, Coincided with Enhanced Fat Storage in Livers of WTFA and KOFA as Well as of KOMA Mice
3.4. Livers of WTFA and KOMA Mice Presented Damage-Associated Signs of Tissue Remodeling
3.5. The Immune-Deficient Phenotype Favored Lipid Storage in Isolated Hepatocytes
3.6. Isolated Hepatocytes from KOMA Mice Featured Low Lipogenic and Low Fatty Acid Utilization Capacity
3.7. Adipose Tissue-Derived Adipokines and Cytokines Potentially Mediate Interactions with the Liver
4. Discussion
4.1. Age-Related Mechanisms to Promote Adipose Tissue Pathologies in Adult Mice
4.2. Hepatic Mechanisms Involved in Increased Lipid Storage in Old Mice
5. Conclusions/Hypothesis
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Wildtype | Knockout | |||
---|---|---|---|---|
Female | Male | Female | Male | |
Young | 13.7 ± 0.47 weeks | 14.3 ± 0.48 weeks | 13.8 ± 0.62 weeks | 13.6 ± 0.52 weeks |
Mean weight [g] | 22.11 ± 0.18 | 26.77 ± 0.55 | 21.94 ± 0.27 | 25.64 ± 0.47 |
Group abbreviation | WTFY | WTMY | KOFY | KOMY |
Adult | 29.3 ± 0.49 weeks | 29.0 ± 1.26 weeks | 29.8 ± 1.47 weeks | 30.3 ± 0.77 weeks |
Mean weight [g] | 23.81 ± 1.13 | 31.44 ± 0.69 | 27.44 ± 0.98 | 32.93 ± 1.16 |
Group abbreviation | WTFA | WTMA | KOFA | KOMA |
Gene | Accession No. | Forward Primer 5′ → 3′ | Reverse Primer 5′ → 3′ |
---|---|---|---|
ACLY | NM_001199296.1 | CCCAAGTCCAAGATCCCTGC | CTGCTTGTGATCCCCAGTGA |
Albumin | NM_009654.4 | CCAATCCTCCCGCATGCTAC | GCGAACTAGAATGGCATTTTGGAA |
B2M | NM_009735.3 | TCTACTGGGATCGAGACATGTGA | ATTGCTATTTCTTTCTGCGTGCAT |
CPT1A | NM_013495.2 | CCATGATGGACCCCACAACA | ATGGCTCAGACAGTACCTCCT |
FABP1 | NM_017399.4 | GGAAAAAGTCAAGGCAGTCGTC | CTCTTGTAGACAATGTCGCCC |
FASN | NM_007988.3 | TGCACCTCACAGGCATCAAT | GTCCCACTTGATGTGAGGGG |
HPRT1 | NM_013556.2 | ACAGGCCAGACTTTGTTGGAT | TGCAGATTCAACTTGCGCTC |
PPARα | NM_011144.6 | GTTCACGCATGTGAAGGCTG | AGCGAATTGCATTGTGTGACAT |
SREBP1c | NM_011480.4 | GATTTGGCCCGGGGAGATTT | TGGCGGATGAGGTTCCAAAG |
Wildtype C57BL/6N | Knockout Pfp/Rag2−/− | Significance | |||||||
---|---|---|---|---|---|---|---|---|---|
Young (WTMY) | Adult (WTMA) | Young (KOMY) | Adult (KOMA) | ||||||
Relative Mean Pixel Density/mg Serum Protein | |||||||||
Mean | SEM | Mean | SEM | Mean | SEM | Mean | SEM | P | |
Adiponectin | 50.10 | 0.38 | 51.20 | 0.26 | 51.67 | 1.07 | 51.05 | 0.14 | |
AgRP | 1.82 | 0.89 | 0.76 | 0.28 | 2.53 | 0.75 | 0.47 | 0.24 | KOMY/KOMA 0.004 |
ANGPL3 | 11.90 | 1.62 | 16.10 | 0.50 | 21.51 | 6.80 | 23.82 | 1.30 | WTMY/KOMY 0.022 WTMA/KOMA 0.001 |
CRP | 38.79 | 3.76 | 44.95 | 1.61 | 44.08 | 4.82 | 48.81 | 0.83 | |
DPPIV | 11.86 | 2.16 | 11.08 | 0.61 | 16.59 | 5.47 | 21.62 | 1.58 | WTMY/KOMY 0,043 WTMA/KOMA 0.001 |
Endocan | 2.34 | 0.27 | 2.55 | 0.15 | 3.35 | 1.01 | 2.83 | 0.42 | WTMY/KOMY 0.033 |
FetuinA | 22.87 | 2.52 | 18.28 | 1.17 | 31.95 | 7.29 | 25.19 | 1.25 | WTMY/KOMY 0,034 WTMA/KOMA 0.007 |
FGFacidic | 3.28 | 0.58 | 1.22 | 0.12 | 4.82 | 2.55 | 0.93 | 0.22 | WTMY/WTMA 0.013 |
ICAM1 | 14.53 | 1.86 | 10.26 | 1.04 | 19.46 | 6.80 | 18.31 | 0.37 | WTMA/KOMA 0.000 |
IGFI | 37.22 | 5.83 | 21.46 | 5.40 | 40.62 | 9.08 | 49.75 | 0.23 | WTMA/KOMA 0.013 |
IGFII | 4.02 | 0.92 | 3.98 | 0.15 | 5.41 | 1.08 | 4.96 | 0.59 | |
IGFBP1 | 8.31 | 2.25 | 32.31 | 6.15 | 12.05 | 4.98 | 9.02 | 1.83 | WTMY/WTMA 0.011 WTMA/KOMA 0.011 |
IGFBP2 | 29.03 | 3.56 | 35.86 | 0.82 | 36.38 | 10.66 | 48.53 | 0.73 | WTMY/KOMY 0.015 WTMA/KOMA 0.000 |
IGFBP3 | 43.01 | 2.98 | 47.01 | 0.85 | 42.05 | 6.59 | 50.82 | 0.23 | WTMA/KOMA 0.005 |
IGFBP5 | 4.47 | 0.57 | 5.13 | 0.22 | 8.83 | 3.02 | 6.34 | 0.65 | WTMY/KOMY 0.014 KOMY/KOMA 0.044 |
IGFBP6 | 18.08 | 3.13 | 20.75 | 2.53 | 23.59 | 9.55 | 37.90 | 4.73 | WTMA/KOMA 0.019 |
IL11 | 1.14 | 0.10 | 1.59 | 0.27 | 2.95 | 1.21 | 0.68 | 0.17 | WTMA/KOMA 0.030 |
Leptin | 1.73 | 0.21 | 1.17 | 0.26 | 2.83 | 1.21 | 2.72 | 0.53 | WTMA/KOMA 0.039 |
Liopcalin2 | 15.96 | 1.33 | 18.60 | 2.11 | 29.45 | 9.48 | 19.83 | 1.58 | |
MCSF | 3.35 | 0.89 | 5.60 | 0.87 | 5.69 | 1.85 | 6.16 | 0.59 | WTMY/KOMY 0.037 |
OncostatinM | 0.82 | 0.16 | 1.64 | 0.22 | 3.02 | 1.01 | 1.14 | 0.08 | WTMY/WTMA 0.023 |
Pentraxin2 | 5.29 | 1.94 | 9.56 | 1.82 | 16.90 | 7.17 | 5.40 | 1.02 | |
Pentraxin3 | 2.13 | 0.42 | 2.37 | 0.34 | 4.32 | 1.63 | 2.11 | 0.24 | WTMY/KOMY 0.038 KOMY/KOMA 0.031 |
RBP4 | 12.34 | 1.14 | 10.30 | 0.98 | 16.72 | 4.68 | 12.37 | 1.01 | WTMY/KOMY 0.047 |
Resistin | 25.96 | 4.31 | 24.51 | 3.03 | 28.58 | 11.08 | 48.34 | 1.17 | WTMA/KOMA 0.000 |
SerpinE1 | 1.75 | 0.31 | 2.06 | 0.39 | 3.11 | 1.15 | 0.85 | 0.15 | WTMA/KOMA 0.028 KOMY/KOMA 0.017 |
TIMP1 | 0.52 | 0.10 | 0.93 | 0.20 | 2.71 | 0.99 | 0.50 | 0.11 |
Knockout Pfp/Rag2−/− | Significance | ||||
---|---|---|---|---|---|
Young (KOMY) | Adult (KOMA) | ||||
Relative Mean Pixel Density/mg Protein | |||||
Mean | SEM | Mean | SEM | p | |
Adiponectin | 249.76 | 1.05 | 247.81 | 3.50 | |
AgRP | 8.44 | 1.35 | 12.52 | 0.88 | |
ANGPL3 | 64.21 | 3.45 | 72.86 | 11.18 | |
CRP | 249.80 | 0.27 | 249.49 | 1.34 | |
DPPIV | 133.98 | 9.61 | 139.65 | 10.08 | |
Endocan | 38.38 | 8.63 | 63.27 | 8.99 | |
FetuinA | 183.56 | 11.24 | 196.04 | 6.99 | |
FGFacidic | 250.70 | 0.85 | 249.87 | 0.33 | |
FGF21 | 14.39 | 2.75 | 24.10 | 1.69 | 0.024 |
HGF | 15.26 | 4.69 | 26.14 | 3.40 | |
ICAM1 | 225.11 | 8.89 | 238.95 | 4.28 | |
IGFI | 23.40 | 3.83 | 33.52 | 6.00 | |
IGFII | 14.10 | 0.89 | 17.69 | 2.16 | |
IGFBP1 | 63.02 | 18.20 | 31.54 | 5.64 | |
IGFBP2 | 135.32 | 5.14 | 161.04 | 23.43 | |
IGFBP3 | 211.48 | 6.13 | 230.40 | 7.45 | |
IGFBP5 | 60.57 | 6.19 | 82.33 | 1.99 | 0.015 |
IGFBP6 | 241.15 | 5.05 | 249.88 | 0.67 | |
IL6 | 9.57 | 1.81 | 13.54 | 1.48 | |
IL10 | 14.67 | 1.88 | 23.60 | 2.49 | 0.029 |
IL11 | 15.93 | 2.44 | 22.92 | 1.46 | 0.049 |
Leptin | 141.31 | 27.71 | 225.14 | 7.41 | 0.027 |
LIF | 11.18 | 1.58 | 20.27 | 3.36 | 0.050 |
Liopcalin2 | 249.91 | 1.90 | 242.53 | 4.43 | |
MCP1 | 23.25 | 4.65 | 43.67 | 8.51 | |
MCSF | 47.88 | 6.20 | 63.50 | 2.23 | 0.056 |
OncostatinM | 14.31 | 1.64 | 16.99 | 2.05 | |
Pentraxin2 | 23.80 | 2.94 | 19.12 | 2.71 | |
Pentraxin3 | 32.22 | 3.04 | 43.15 | 4.21 | |
Pref1 | 14.04 | 2.54 | 24.49 | 2.46 | 0.025 |
RAGE | 19.37 | 3.23 | 21.24 | 2.43 | |
RANTES | 17.97 | 2.22 | 32.60 | 5.21 | 0.041 |
RBP4 | 94.19 | 9.55 | 92.23 | 4.47 | |
Resistin | 248.49 | 1.82 | 245.53 | 1.03 | |
SerpinE1 | 60.81 | 14.27 | 88.45 | 26.72 | |
TIMP1 | 28.02 | 3.93 | 47.08 | 11.84 | |
TNFa | 8.52 | 1.11 | 12.33 | 1.59 | |
VEGF | 55.13 | 14.65 | 55.56 | 2.77 |
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Winkler, S.; Hempel, M.; Hsu, M.-J.; Gericke, M.; Kühne, H.; Brückner, S.; Erler, S.; Burkhardt, R.; Christ, B. Immune-Deficient Pfp/Rag2−/− Mice Featured Higher Adipose Tissue Mass and Liver Lipid Accumulation with Growing Age than Wildtype C57BL/6N Mice. Cells 2019, 8, 775. https://doi.org/10.3390/cells8080775
Winkler S, Hempel M, Hsu M-J, Gericke M, Kühne H, Brückner S, Erler S, Burkhardt R, Christ B. Immune-Deficient Pfp/Rag2−/− Mice Featured Higher Adipose Tissue Mass and Liver Lipid Accumulation with Growing Age than Wildtype C57BL/6N Mice. Cells. 2019; 8(8):775. https://doi.org/10.3390/cells8080775
Chicago/Turabian StyleWinkler, Sandra, Madlen Hempel, Mei-Ju Hsu, Martin Gericke, Hagen Kühne, Sandra Brückner, Silvio Erler, Ralph Burkhardt, and Bruno Christ. 2019. "Immune-Deficient Pfp/Rag2−/− Mice Featured Higher Adipose Tissue Mass and Liver Lipid Accumulation with Growing Age than Wildtype C57BL/6N Mice" Cells 8, no. 8: 775. https://doi.org/10.3390/cells8080775