A Short-Term High-Fat Diet Worsens Insulin Sensitivity with Changes in Metabolic Parameters in Non-Obese Japanese Men
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Participants
2.2. Study Design and Methods
2.3. Dietary and Physical Activity Manipulations
2.4. 1H-MRS and MRI
2.5. Two-Step Hyperinsulinemic Euglycemic Clamp Procedure
2.6. Determination of Tissue-Specific Insulin Sensitivity and MCRI with the Clamp Test
2.7. Biochemical Tests
2.8. Fecal Sample Evaluation
2.9. 16S Metagenomic Sequencing
2.10. Whole-Body Indirect Calorimetry
2.11. Meal Tolerance Test
2.12. Statistical Analysis
3. Results
3.1. Anthropometric and Metabolic Characteristics before and after Short-Term HCHFD
3.2. Change in Fat Distribution after Short-Term HCHFD
3.3. Insulin Sensitivity Evaluated with a Two-Step Hyperinsulinemic Euglycemic Clamp at Baseline and after Short-Term HCHFD
3.4. Meal Tolerance Test
3.5. Effects of HCHFD on Gut Microbiota
3.6. Energy Metabolism Evaluated Using the Metabolic Chamber at Baseline and after HCHFD
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Baseline | After HCHFD | p Value | |
---|---|---|---|
Body weight (kg) | 61.6 ± 6.1 | 62.0 ± 6.1 | 0.021 |
Fat free mass (kg) | 52.8 ± 5.3 | 53.4 ± 5.4 | 0.015 |
Body mass index (kg/m2) | 20.6 ± 1.8 | 20.7 ± 1.7 | 0.019 |
Fat mass (kg) | 6.7 ± 1.4 | 6.6 ± 1.5 | 0.727 |
Percent body fat (%) | 13.1 ± 3.1 | 12.7 ± 3.1 | 0.116 |
Serum insulin (μIU/mL) | 4.7 ± 1.2 | 5.5 ± 2.4 | 0.274 |
C-peptide (ng/mL) | 1.1 ± 0.2 | 1.2 ± 0.3 | 0.099 |
Plasma glucose (mg/dL) | 86.6 ± 5.6 | 90.5 ± 5.4 | 0.012 |
Free fatty acids (μEq/L) | 665.0 ± 229.4 | 377.3 ± 180.6 | <0.001 |
Total cholesterol (mg/dL) | 152.8 ± 19.7 | 161.0 ± 23.2 | 0.022 |
High-density lipoprotein cholesterol (mg/dL) | 52.6 ± 11.0 | 59.3 ± 11.0 | 0.001 |
Low-density lipoprotein cholesterol (mg/dL) | 88.2 ± 19.6 | 92.0 ± 21.6 | 0.163 |
Triglycerides (mg/dL) | 66.5 ± 14.8 | 70.5 ± 28.4 | 0.412 |
Aspartate aminotransferase (U/L) | 18.7 ± 5.2 | 18.4 ± 5.2 | 0.689 |
Alanine aminotransferase (U/L) | 15.6 ± 6.5 | 17.4 ± 6.9 | 0.095 |
Alkaline phosphatase (U/L) | 189.5 ± 44.4 | 203.6 ± 47.0 | 0.073 |
γ-Glutamyl transpeptidase (U/L) | 15.9 ± 3.9 | 14.6 ± 3.2 | 0.007 |
Total bile acid (μmol/L) | 5.4 ± 5.0 | 7.7 ± 8.5 | 0.040 |
Acetoacetic acid (μmol/L) | 29.5 ± 23.3 | 19.1 ± 11.5 | 0.021 |
3-hydroxyacetic acid (μmol/L) | 82.6 ± 72.4 | 33.2 ± 23.4 | <0.001 |
Total ketone bodies (μmol/L) | 112.1 ± 95.3 | 52.3 ± 34.2 | 0.002 |
Total adiponectin (μg/mL) | 5.37 ± 2.15 | 5.80 ± 2.20 | 0.004 |
High-molecular-weight adiponectin (μg/mL) | 1.93 ± 1.30 | 2.14 ± 1.42 | 0.021 |
FGF-21 (pg/mL) | 107.5 ± 60.0 | 169.7 ± 107.4 | 0.001 |
Interleukin 6 (pg/mL) | 1.2 ± 2.3 | 1.2 ± 1.7 | 0.984 |
Leptin (ng/mL) | 4.5 ± 1.6 | 5.0 ± 1.7 | 0.048 |
Monocyte chemoattractant protein-1 (pg/mL) | 200.1 ± 46.7 | 200.3 ± 32.8 | 0.768 |
LBP (μg/mL) | 4.9 ± 0.7 | 5.6 ± 0.7 | 0.006 |
High-sensitivity CRP (ng/mL) | 157.0 ± 308.8 | 224.3 ± 228.6 | 0.073 |
Tumor necrosis factor alpha (pg/mL) | 0.70 ± 0.18 | 0.68 ± 0.16 | 0.365 |
Basal metabolic rate (kcal/min) | 0.94 ± 0.12 | 0.95 ± 0.12 | 0.509 |
Basal RQ | 0.89 ± 0.08 | 0.92 ± 0.05 | 0.103 |
Sleep energy expenditure (kcal/min) | 0.87 ± 0.09 | 0.88 ± 0.09 | 0.407 |
Sleep RQ | 0.83 ± 0.03 | 0.87 ± 0.04 | <0.001 |
Baseline | After HCHFD | p Value | |
---|---|---|---|
Intrahepatic lipid (%) | 0.5 ± 0.4 | 1.5 ± 1.0 | <0.001 |
Intramyocellular lipid-TA (S-fat/Cre) | 1.7 ± 1.2 | 2.5 ± 1.3 | 0.009 |
Intramyocellular lipid-SOL (S-fat/Cre) | 5.2 ± 2.7 | 6.8 ± 2.7 | 0.005 |
Abdominal visceral fat area (cm2) | 46.0 ± 11.2 | 46.6 ± 10.2 | 0.476 |
Abdominal subcutaneous fat area (cm2) | 71.7 ± 26.4 | 73.7 ± 26.8 | 0.217 |
SSSI during the first step (μU/mL) | 17.1 ± 2.1 | 18.4 ± 2.7 | 0.019 |
SSsc during the first step (ng/mL) | 0.72 ± 0.25 | 0.82 ± 0.32 | 0.019 |
SSSI during the second step (μU/mL) | 31.5 ± 4.1 | 34.4 ± 4.9 | 0.002 |
SSsc during the second step (ng/mL) | 0.60 ± 0.27 | 0.73 ± 0.28 | 0.006 |
MCRI during the second step (mL/min per m2) | 692.4 ± 94.1 | 653.1 ± 99.7 | 0.004 |
Basal EGP (mg/m2/min) | 76.9 ± 3.4 | 79.4 ± 4.7 | 0.023 |
% reduction in EGP during the first step (%/μU) | 75.2 ± 11.6 | 73.5 ± 13.6 | 0.419 |
% reduction in EGP/SSSI during the first step (%/μU·mL−1) | 4.46 ± 0.85 | 4.09 ± 0.97 | 0.044 |
Rd during the second step (mg/kg FFM/min−1) | 7.49 ± 1.20 | 7.67 ± 1.29 | 0.268 |
Rd/SSSI during the second step (mg/kg FFM·min−1/μU·mL−1) | 0.24 ± 0.06 | 0.23 ± 0.05 | 0.042 |
Adipose tissue insulin resistance index | 3209.5 ± 1519.6 | 2345.1 ± 2012.5 | 0.023 |
Baseline | After HCHFD | p Value | |
---|---|---|---|
AUC-glucose (mg/dL × min × 103) | 26.9 ± 27.0 | 25.9 ± 2.7 | 0.131 |
AUC-FFA (μEq/L × min × 103) | 41.6 ± 8.2 | 32.2 ± 6.3 | <0.001 |
AUC-insulin (IU/mL × min × 103) | 9.0 ± 3.8 | 7.7 ± 2.7 | 0.039 |
AUC-CPR (ng/mL × min × 103) | 1.3 ± 0.3 | 1.1 ± 0.3 | 0.007 |
AUC-glucagon (pg/mL × min × 103) | 7.4 ± 2.8 | 8.3 ± 3.1 | 0.140 |
AUC-GIP (pmol/L × min × 103) | 10.5 ± 2.8 | 10.5 ± 3.0 | 0.986 |
AUC-GLP-1 (pmol/L × min × 103) | 0.85 ± 0.38 | 0.90 ± 0.40 | 0.339 |
Insulin sensitivity index (comp) | 10.0 ± 5.5 | 9.5 ± 4.6 | 0.794 |
Insulinogenic index | 0.9 ± 0.3 | 1.3 ± 0.6 | <0.001 |
Insulinogenic index (c-peptide) | 0.072 ± 0.022 | 0.101 ± 0.049 | <0.001 |
Baseline | After HCHFD | p Value | |
---|---|---|---|
Actinobacteria (%) | 6.89 ± 4.86 | 9.73 ± 5.66 | 0.005 |
Bacteroidetes (%) | 25.19 ± 7.88 | 25.79 ± 9.00 | 0.970 |
Firmicutes (%) | 63.05 ± 9.72 | 60.91 ± 11.14 | 0.232 |
Fusobacteria (%) | 1.75 ± 2.76 | 1.41 ± 2.59 | 0.156 |
Proteobacteria (%) | 2.82 ± 3.33 | 2.16 ± 1.04 | 0.970 |
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Kadowaki, S.; Tamura, Y.; Sugimoto, D.; Kaga, H.; Suzuki, R.; Someya, Y.; Yamasaki, N.; Sato, M.; Kakehi, S.; Kanazawa, A.; et al. A Short-Term High-Fat Diet Worsens Insulin Sensitivity with Changes in Metabolic Parameters in Non-Obese Japanese Men. J. Clin. Med. 2023, 12, 4084. https://doi.org/10.3390/jcm12124084
Kadowaki S, Tamura Y, Sugimoto D, Kaga H, Suzuki R, Someya Y, Yamasaki N, Sato M, Kakehi S, Kanazawa A, et al. A Short-Term High-Fat Diet Worsens Insulin Sensitivity with Changes in Metabolic Parameters in Non-Obese Japanese Men. Journal of Clinical Medicine. 2023; 12(12):4084. https://doi.org/10.3390/jcm12124084
Chicago/Turabian StyleKadowaki, Satoshi, Yoshifumi Tamura, Daisuke Sugimoto, Hideyoshi Kaga, Ruriko Suzuki, Yuki Someya, Nozomu Yamasaki, Motonori Sato, Saori Kakehi, Akio Kanazawa, and et al. 2023. "A Short-Term High-Fat Diet Worsens Insulin Sensitivity with Changes in Metabolic Parameters in Non-Obese Japanese Men" Journal of Clinical Medicine 12, no. 12: 4084. https://doi.org/10.3390/jcm12124084