Effects of Whole-Body Adenylyl Cyclase 5 (Adcy5) Deficiency on Systemic Insulin Sensitivity and Adipose Tissue
Abstract
:1. Introduction
2. Results
2.1. Adcy5–/– Mice Are Not Protected against Obesity
2.2. Adcy5 Deletion Effects on Glucose Tolerance, Insulin Sensitivity and Serum Parameters
2.3. Consequences of Adcy5–/– on AT Morphology
2.4. Adcy5–/– Mice Are Characterized by a Distinct EWAT Gene Expression Signature
2.5. Adcy5–/– Affects Activity and Energy Expenditure
3. Discussion
4. Materials and Methods
4.1. Animal Studies
4.2. Generation of Adenylyl Cyclase Type 5 Knockout Mice
4.3. Phenotypic Characterization
4.4. Adipose Tissue Histology
4.5. RNA Isolation and Tissue-Specific mRNA Expression
4.6. Adipose Tissue Microarray Analyses
4.7. Statistical Analyses
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
36b4 | Rplp0, ribosomal protein, large, P0 |
ACC | Acetyl-CoA carboxylase |
Adcy | Adenylyl cyclase |
AMPK | AMP-activated protein kinase |
AT | Adipose tissue |
Atp1a3 | Sodium/potassium-transporting ATPase subunit alpha-3 |
BAT | Brown adipose tissue |
BMI | Body mass index |
cAMP | Cyclic adenosine monophosphate |
CD | Chow diet |
CD11c, CD40, CD68, CD163 | Cluster of differentiation 11c, 40, 68 and 163 |
Ctrl | Control |
DIO | Diet-induced obesity |
EDTA | Ethylenediaminetetraacetic acid |
EE | Energy expenditure |
Elovl6 | Elongation of very long chain fatty acids protein 6 |
eWAT | Epigonadal white adipose tissue |
Fasn | Fatty acid synthase |
Gpd1 | Glycerol-3-phosphate dehydrogenase |
GTT | Glucose tolerance test |
HbA1c | Glycated hemoglobin A1c |
HDL | High density lipoprotein |
HFD | High-fat diet |
i.p. | Intraperitoneal |
IGF-1 | Insulin-like growth factor 1 |
IL-17f | Interleukin 17f |
ingWAT | Inguinal white adipose tissue |
ITT | Insulin tolerance test |
LDL | Low density lipoprotein |
LIMMA | Linear models for microarray data |
Mid1 | Midline 1 |
Mid1ip1 | Mid1-interacting protein 1, also Mig12 or Spot14R |
Nnt | Nicotinamide nucleotide transhydrogenase |
PKA | Protein kinase A |
PPARg | Peroxisome proliferator-activated receptor gamma |
qRT-PCR | Quantitative real-time polymerase chain reaction |
RER | Respiratory exchange ratio |
RING | Really interesting new gene |
RMA | Robust multichip average |
Slc2a5 | Solute carrier family 2, facilitated glucose transporter member 5 |
SNP | Single nucleotide polymorphism |
T2D | Type 2 diabetes mellitus |
TAC | Transcriptome analysis console |
Thrsp | Thyroid hormone-inducible hepatic protein |
Tkt | Transketolase |
TRIM | Tripartite motive family |
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CD | HFD | |||||
---|---|---|---|---|---|---|
Ctrl | Adcy5–/– | n | Ctrl | Adcy5–/– | n | |
Serum Lipids | ||||||
Triglycerides (mmol/L) | 1.07 ± 0.32 | 1.10 ± 0.20 | 4 vs. 5 | 1.03 ± 0.47 | 1.31 ± 0.22 | 5 vs. 5 |
Cholesterol (mmol/L) | 2.16 ± 0.22 | 1.53 ± 0.23 | 5 vs. 5 | 2.98 ± 0.28 | 3.50 ± 0.30 | 5 vs. 5 |
HDL-cholesterol (mmol/L) | 1.67 ± 0.20 | 1.21 ± 0.20 | 5 vs. 5 | 2.23 ± 0.27 | 2.78 ± 0.26 | 5 vs. 5 |
LDL-cholesterol (mmol/L) | 0.35 ± 0.07 | 0.18 ± 0.03 | 5 vs. 5 | 0.73 ± 0.07 | 0.58 ± 0.07 | 5 vs. 5 |
FFA (mmol/L) | 1.50 ± 0.30 | 1.67 ± 0.35 | 5 vs. 5 | 1.71 ± 0.23 | 1.82 ± 0.26 | 5 vs. 5 |
OLINK Protein serum Analysis (Normalized Protein Expression (AU)) | ||||||
Il17f | 3.43 ± 0.20 | 1.84 ± 0.26 | 3 vs. 4 | 5.05 ± 0.80 | 2.79 ± 0.23 | 3 vs. 3 |
Glucose Homeostasis | ||||||
C-peptide (ng/mL) | 0.60 ± 0.10 | 0.40 ± 0.19 | 5 vs. 5 | 1.18 ± 0.53 | 1.11 ± 0.35 | 5 vs. 5 |
Insulin (µg/L) | 0.28 ± 0.12 | 0.19 ± 0.03 | 5 vs. 5 | 0.69 ± 0.63 | 0.65 ± 0.48 | 5 vs. 5 |
Adiponectin (µg/mL) | 208.5 ± 56.1 | 242.5 ± 105.7 | 5 vs. 5 | 140.1 ± 8.3 | 145.6 ± 4.3 | 5 vs. 5 |
Leptin (ng/mL) | 3.51 ± 1.12 | 3.96 ± 5.55 | 5 vs. 5 | 7.02 ± 2.83 | 22.80 ± 10.61 | 5 vs. 5 |
Leptin/body weight (ng/mL/g) | 0.15 ± 0.04 | 0.17 ± 0.24 | 5 vs. 5 | 0.27 ± 0.10 | 0.69 ± 0.31 | 5 vs. 5 |
Fasting glucose (mmol/L) | 4.57 ± 1.14 | 4.23 ± 1.34 | 12 vs. 12 | 4.96 ± 1.43 | 6.10 ± 1.85 | 14 vs. 11 |
HbA1c (%) | 4.20 ± 0.12 | 3.94 ± 0.18 | 12 vs. 11 | 4.09 ± 0.14 | 4.09 ± 0.14 | 13 vs. 11 |
CD | HFD | |||||
---|---|---|---|---|---|---|
Ctrl | Adcy5–/– | n | Ctrl | Adcy5–/– | n | |
Serum Lipids | ||||||
Triglycerides (mmol/L) | 1.08 ± 0.09 | 1.11 ± 0.22 | 5 vs. 5 | 1.54 ± 0.10 | 5 vs. 5 | |
Cholesterol (mmol/L) | 2.62 ± 0.49 | 2.07 ± 0.10 | 5 vs. 5 | 4.30 ± 0.15 | 5.05 ± 0.40 | 5 vs. 5 |
HDL-cholesterol (mmol/L) | 2.07 ± 0.33 | 1.77 ± 0.09 | 5 vs. 5 | 3.28 ± 0.14 | 3.77 ± 0.20 | 5 vs. 5 |
LDL-cholesterol (mmol/L) | 0.39 ± 0.10 | 0.15 ± 0.03 | 5 vs. 5 | 0.83 ± 0.20 | 1.04 ± 0.15 | 5 vs. 5 |
FFA (mmol/L) | 1.53 ± 0.09 | 1.47 ± 0.26 | 5 vs. 5 | 1.86 ± 0.08 | 1.99 ± 0.19 | 5 vs. 5 |
OLINK Protein Serum Analysis (Normalized Protein Expression (AU)) | ||||||
Il17f | 3.17 ± 0.28 | 1.56 ± 0.23 | 3 vs. 4 | 5.21 ± 1.39 | 3.14 ± 0.89 | 3 vs. 4 |
Glucose Homeostasis | ||||||
C-peptide (ng/mL) | 1.08 ± 0.41 | 0.45 ± 0.11 | 5 vs. 5 | 2.28 ± 1.37 | 4.56 ± 1.47 | 5 vs. 5 |
Insulin (µg/L) | 0.34 ± 0.15 | 0.17 ± 0.06 | 5 vs. 5 | 1.47 ± 1.05 | 1.81 ± 0.75 | 4 vs. 5 |
Adiponectin (µg/mL) | 135.2 ± 13.1 | 107.9 ± 20.7 | 5 vs. 5 | 88.3 ± 7.9 | 85.4 ± 10.7 | 5 vs. 5 |
Leptin (ng/mL) | 7.69 ± 4.40 | 2.80 ± 1.26 | 5 vs. 4 | 39.8 ± 1.30 | 40.4 ± 1.17 | 5 vs. 5 |
Leptin/body weight (ng/mL/g) | 0.25 ± 0.12 | 0.10 ± 0.05 | 5 vs. 4 | 1.00 ± 0.05 | 0.92 ± 0.02 | 5 vs. 5 |
Fasting glucose (mmol/L) | 4.94 ± 1.44 | 3.44 ± 0.55 | 12 vs. 12 | 5.28 ± 2.20 | 6.18 ± 1.37 | 14 vs. 13 |
HbA1c (%) | 4.48 ± 0.15 | 4.29 ± 0.13 | 12 vs. 12 | 4.31 ± 0.17 | 4.34 ± 0.15 | 8 vs. 13 |
HOMA-β (%) | 86.6 ± 38.3 | 190.2 ± 15.3 | 5 vs. 5 | 318 ± 265 | 281 ± 118 | 4 vs. 5 |
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Dommel, S.; Hoffmann, A.; Berger, C.; Kern, M.; Klöting, N.; Kannt, A.; Blüher, M. Effects of Whole-Body Adenylyl Cyclase 5 (Adcy5) Deficiency on Systemic Insulin Sensitivity and Adipose Tissue. Int. J. Mol. Sci. 2021, 22, 4353. https://doi.org/10.3390/ijms22094353
Dommel S, Hoffmann A, Berger C, Kern M, Klöting N, Kannt A, Blüher M. Effects of Whole-Body Adenylyl Cyclase 5 (Adcy5) Deficiency on Systemic Insulin Sensitivity and Adipose Tissue. International Journal of Molecular Sciences. 2021; 22(9):4353. https://doi.org/10.3390/ijms22094353
Chicago/Turabian StyleDommel, Sebastian, Anne Hoffmann, Claudia Berger, Matthias Kern, Nora Klöting, Aimo Kannt, and Matthias Blüher. 2021. "Effects of Whole-Body Adenylyl Cyclase 5 (Adcy5) Deficiency on Systemic Insulin Sensitivity and Adipose Tissue" International Journal of Molecular Sciences 22, no. 9: 4353. https://doi.org/10.3390/ijms22094353