Midregional Proadrenomedullin Can Reflect the Accumulation of Visceral Adipose Tissue—A Key to Explaining the Obesity Paradox
Abstract
:1. Introduction
2. Materials and Methods
2.1. Participants
2.2. Clinical and Biochemical Analysis
2.3. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Acknowledgments
Conflicts of Interest
References
- Velasquez-Rodriguez, C.M.; Velasquez-Villa, M.; Gomez-Ocampo, L.; Bermudez-Cardona, J. Abdominal obesity and low physical activity are associated with insulin resistance in overweight adolescents: a cross-sectional study. BMC Pediatrics 2014, 14, 258. [Google Scholar] [CrossRef] [Green Version]
- Pal, S.; Radavelli-Bagatini, S. Association of arterial stiffness with obesity in Australian women: a pilot study. J. Clin. Hypertens. (Greenwich) 2013, 15, 118–123. [Google Scholar] [CrossRef] [PubMed]
- Abbasi, A.; Juszczyk, D.; van Jaarsveld, C.H.M.; Gulliford, M.C. Body Mass Index and Incident Type 1 and Type 2 Diabetes in Children and Young Adults: A Retrospective Cohort Study. J. Endocr. Soc. 2017, 1, 524–537. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chooi, Y.C.; Ding, C.; Magkos, F. The epidemiology of obesity. Metabolism 2019, 92, 6–10. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wildman, R.P.; Muntner, P.; Reynolds, K.; McGinn, A.P.; Rajpathak, S.; Wylie-Rosett, J.; Sowers, M.R. The obese without cardiometabolic risk factor clustering and the normal weight with cardiometabolic risk factor clustering: prevalence and correlates of 2 phenotypes among the US population (NHANES 1999-2004). Arch. Intern. Med. 2008, 168, 1617–1624. [Google Scholar] [CrossRef] [Green Version]
- Ahima, R.S.; Lazar, M.A. Physiology. The health risk of obesity--better metrics imperative. Science 2013, 341, 856–858. [Google Scholar] [CrossRef]
- Bosello, O.; Vanzo, A. Obesity paradox and aging. Eat. Weight Disord. 2019. [Google Scholar] [CrossRef]
- Kitamura, K.; Kangawa, K.; Kawamoto, M.; Ichiki, Y.; Nakamura, S.; Matsuo, H.; Eto, T. Adrenomedullin: A novel hypotensive peptide isolated from human pheochromocytoma. Biochem. Biophys. Res. Commun. 1993, 192, 553–560. [Google Scholar] [CrossRef] [PubMed]
- Koyama, T.; Sakurai, T.; Kamiyoshi, A.; Ichikawa-Shindo, Y.; Kawate, H.; Shindo, T. Adrenomedullin-RAMP2 System in Vascular Endothelial Cells. J. Atheroscler. Thromb. 2015, 22, 647–653. [Google Scholar] [CrossRef] [Green Version]
- Cheung, B.M.; Tang, F. Adrenomedullin: Exciting new horizons. Recent Pat. Endocr. Metab. Immune Drug Discov. 2012, 6, 4–17. [Google Scholar] [CrossRef] [PubMed]
- Li, Y.; Jiang, C.; Wang, X.; Zhang, Y.; Shibahara, S.; Takahashi, K. Adrenomedullin is a novel adipokine: Adrenomedullin in adipocytes and adipose tissues. Peptides 2007, 28, 1129–1143. [Google Scholar] [CrossRef] [PubMed]
- Paulmyer-Lacroix, O.; Desbriere, R.; Poggi, M.; Achard, V.; Alessi, M.C.; Boudouresque, F.; Ouafik, L.; Vuaroqueaux, V.; Labuhn, M.; Dutourand, A.; et al. Expression of adrenomedullin in adipose tissue of lean and obese women. Eur. J. Endocrinol. 2006, 155, 177–185. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Del Ry, S.; Cabiati, M.; Bianchi, V.; Caponi, L.; Di Cecco, P.; Marchi, B.; Randazzo, E.; Caselli, C.; Prescimone, T.; Clerico, A.; et al. Mid-regional-pro-adrenomedullin plasma levels are increased in obese adolescents. Eur. J. Nutr. 2016, 55, 1255–1260. [Google Scholar] [CrossRef] [PubMed]
- Vila, G.; Riedl, M.; Maier, C.; Struck, J.; Morgenthaler, N.G.; Handisurya, A.; Prager, G.; Ludvik, B.; Clodi, M.; Luger, A. Plasma MR-proADM correlates to BMI and decreases in relation to leptin after gastric bypass surgery. Obesity 2009, 17, 1184–1188. [Google Scholar] [CrossRef] [PubMed]
- Ohlsson, T.; Nilsson, P.M.; Persson, M.; Melander, O. Midregional proadrenomedullin predicts reduced blood pressure and glucose elevation over time despite enhanced progression of obesity markers. J. Hypertens. 2019, 37, 590–595. [Google Scholar] [CrossRef] [PubMed]
- Meeran, K.; O’Shea, D.; Upton, P.D.; Small, C.J.; Ghatei, M.A.; Byfield, P.H.; Bloom, S.R. Circulating adrenomedullin does not regulate systemic blood pressure but increases plasma prolactin after intravenous infusion in humans: A pharmacokinetic study. J. Clin. Endocrinol. Metab. 1997, 82, 95–100. [Google Scholar] [CrossRef]
- Caruhel, P.; Mazier, C.; Kunde, J.; Morgenthaler, N.G.; Darbouret, B. Homogeneous time-resolved fluoroimmunoassay for the measurement of midregional proadrenomedullin in plasma on the fully automated system B.R.A.H.M.S KRYPTOR. Clin. Biochem. 2009, 42, 725–728. [Google Scholar] [CrossRef]
- Wakai, K.; Hamajima, N.; Okada, R.; Naito, M.; Morita, E.; Hishida, A.; Kawai, S.; Nishio, K.; Yin, G.; Asai, Y.; et al. Profile of Participants and Genotype Distributions of 108 Polymorphisms in a Cross-Sectional Study of Associations of Genotypes With Lifestyle and Clinical Factors: A Project in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. J. Epidemiol. 2011, 21, 223–235. [Google Scholar] [CrossRef] [Green Version]
- Haraguchi, N.; Koyama, T.; Kuriyama, N.; Ozaki, E.; Matsui, D.; Watanabe, I.; Uehara, R.; Watanabe, Y. Assessment of anthropometric indices other than BMI to evaluate arterial stiffness. Hypertens. Res. 2019, 42, 1599–1605. [Google Scholar] [CrossRef]
- Hara, M.; Higaki, Y.; Taguchi, N.; Shinchi, K.; Morita, E.; Naito, M.; Hamajima, N.; Takashima, N.; Suzuki, S.; Nakamura, A.; et al. Effect of the PPARG2 Pro12Ala polymorphism and clinical risk factors for diabetes mellitus on HbA1c in the Japanese general population. J. Epidemiol. 2012, 22, 523–531. [Google Scholar] [CrossRef] [Green Version]
- Oshima, Y.; Shiga, T.; Namba, H.; Kuno, S. Estimation of whole-body skeletal muscle mass by bioelectrical impedance analysis in the standing position. Obes. Res. Clin. Pract. 2010, 4, e1–e7. [Google Scholar] [CrossRef]
- Fox, C.S.; Massaro, J.M.; Hoffmann, U.; Pou, K.M.; Maurovich-Horvat, P.; Liu, C.Y.; Vasan, R.S.; Murabito, J.M.; Meigs, J.B.; Cupples, L.A.; et al. Abdominal visceral and subcutaneous adipose tissue compartments: Association with metabolic risk factors in the Framingham Heart Study. Circulation 2007, 116, 39–48. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bouchi, R.; Takeuchi, T.; Akihisa, M.; Ohara, N.; Nakano, Y.; Nishitani, R.; Murakami, M.; Fukuda, T.; Fujita, M.; Minami, I.; et al. High visceral fat with low subcutaneous fat accumulation as a determinant of atherosclerosis in patients with type 2 diabetes. Cardiovasc. Diabetol. 2015, 14, 136. [Google Scholar] [CrossRef] [Green Version]
- Kaess, B.M.; Pedley, A.; Massaro, J.M.; Murabito, J.; Hoffmann, U.; Fox, C.S. The ratio of visceral to subcutaneous fat, a metric of body fat distribution, is a unique correlate of cardiometabolic risk. Diabetologia 2012, 55, 2622–2630. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Enzi, G.; Gasparo, M.; Biondetti, P.R.; Fiore, D.; Semisa, M.; Zurlo, F. Subcutaneous and visceral fat distribution according to sex, age, and overweight, evaluated by computed tomography. Am. J. Clin. Nutr. 1986, 44, 739–746. [Google Scholar] [CrossRef] [PubMed]
- Geer, E.B.; Shen, W. Gender differences in insulin resistance, body composition, and energy balance. Gend. Med. 2009, 6 (Suppl. 1), 60–75. [Google Scholar] [CrossRef] [Green Version]
- van den Munckhof, I.C.L.; Holewijn, S.; de Graaf, J.; Rutten, J.H.W. Sex differences in fat distribution influence the association between BMI and arterial stiffness. J. Hypertens. 2017, 35, 1219–1225. [Google Scholar] [CrossRef]
- Trujillo, M.E.; Scherer, P.E. Adipose tissue-derived factors: Impact on health and disease. Endocr. Rev. 2006, 27, 762–778. [Google Scholar] [CrossRef] [Green Version]
- Nambu, T.; Arai, H.; Komatsu, Y.; Yasoda, A.; Moriyama, K.; Kanamoto, N.; Itoh, H.; Nakao, K. Expression of the adrenomedullin gene in adipose tissue. Regul. Pept. 2005, 132, 17–22. [Google Scholar] [CrossRef] [Green Version]
- Kawano, S.; Kawagoe, Y.; Kuwasako, K.; Shimamoto, S.; Igarashi, K.; Tokashiki, M.; Kitamura, K.; Kato, J. Gender-related alterations in plasma adrenomedullin level and its correlation with body weight gain. Endocr. Connect. 2015, 4, 43–49. [Google Scholar] [CrossRef] [Green Version]
- Lim, S.C.; Morgenthaler, N.G.; Subramaniam, T.; Wu, Y.S.; Goh, S.K.; Sum, C.F. The relationship between adrenomedullin, metabolic factors, and vascular function in individuals with type 2 diabetes. Diabetes Care 2007, 30, 1513–1519. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kistorp, C.; Bliddal, H.; Goetze, J.P.; Christensen, R.; Faber, J. Cardiac natriuretic peptides in plasma increase after dietary induced weight loss in obesity. BMC Obes. 2014, 1, 24. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pou, K.M.; Massaro, J.M.; Hoffmann, U.; Vasan, R.S.; Maurovich-Horvat, P.; Larson, M.G.; Keaney, J.F., Jr.; Meigs, J.B.; Lipinska, I.; Kathiresan, S.; et al. Visceral and subcutaneous adipose tissue volumes are cross-sectionally related to markers of inflammation and oxidative stress: The Framingham Heart Study. Circulation 2007, 116, 1234–1241. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dandona, P.; Aljada, A.; Bandyopadhyay, A. Inflammation: The link between insulin resistance, obesity and diabetes. Trends Immunol. 2004, 25, 4–7. [Google Scholar] [CrossRef]
- Kato, J.; Kitamura, K. Bench-to-bedside pharmacology of adrenomedullin. Eur. J. Pharmacol. 2015, 764, 140–148. [Google Scholar] [CrossRef]
- Krakauer, N.Y.; Krakauer, J.C. A new body shape index predicts mortality hazard independently of body mass index. PLoS ONE 2012, 7, e39504. [Google Scholar] [CrossRef]
- Koyama, T.; Ochoa-Callejero, L.; Sakurai, T.; Kamiyoshi, A.; Ichikawa-Shindo, Y.; Iinuma, N.; Arai, T.; Yoshizawa, T.; Iesato, Y.; Lei, Y.; et al. Vascular endothelial adrenomedullin-RAMP2 system is essential for vascular integrity and organ homeostasis. Circulation 2013, 127, 842–853. [Google Scholar] [CrossRef]
- Koyama, T.; Kuriyama, N.; Ozaki, E.; Matsui, D.; Watanabe, I.; Takeshita, W.; Iwai, K.; Watanabe, Y.; Nakatochi, M.; Shimanoe, C.; et al. Genetic Variants of RAMP2 and CLR are Associated with Stroke. J. Atheroscler. Thromb. 2017, 24, 1267–1281. [Google Scholar] [CrossRef] [Green Version]
Men | Women | ||||
---|---|---|---|---|---|
n = 727 | n = 1517 | ||||
Mean | SD | Mean | SD | p-Value | |
Age (years) | 59.7 | 10.3 | 57.1 | 9.92 | <0.001 |
BMI (kg/m2) | 23.5 | 2.98 | 21.6 | 3.18 | <0.001 |
VAT (cm2) | 79.9 | 36.0 | 51.3 | 26.6 | <0.001 |
SAT (cm2) | 145 | 50.9 | 130 | 66.4 | <0.001 |
VAT/SAT ratio | 0.552 | 0.187 | 0.427 | 0.182 | <0.001 |
BFM (%) | 23.6 | 4.38 | 30.36 | 4.69 | <0.001 |
SMM (%) | 30.1 | 2.28 | 24.94 | 6.24 | 0.300 |
METs (hours/day) | 14.8 | 11.0 | 15.4 | 10.4 | 0.248 |
Brinkman index | 513 | 557 | 69 | 186 | <0.001 |
Alcohol (g/day) | 22.5 | 28.1 | 6.63 | 13.3 | <0.001 |
Sleep time (hours) | 6.48 | 1.03 | 6.37 | 1.00 | 0.016 |
MR-proADM (nmol/L) | 0.467 | 0.099 | 0.412 | 0.082 | <0.001 |
n | % | n | % | ||
Hypertension | 364 | 50.1 | 440 | 29.0 | <0.001 |
Dyslipidemia | 322 | 44.3 | 675 | 44.5 | 0.482 |
Diabetes | 74 | 10.2 | 49 | 3.2 | <0.001 |
Men | Women | |||
---|---|---|---|---|
Coefficient | p-Value | Coefficient | p-Value | |
BMI | 0.130 | <0.001 | 0.304 | <0.001 |
VAT | 0.277 | <0.001 | 0.365 | <0.001 |
SAT | 0.161 | <0.001 | 0.333 | <0.001 |
VAT/SAT ratio | 0.225 | <0.001 | 0.062 | 0.015 |
BFM | 0.336 | <0.001 | 0.435 | <0.001 |
SMM | −0.485 | <0.001 | −0.413 | <0.001 |
Men | Women | |||||||
---|---|---|---|---|---|---|---|---|
Stepwise | Stepwise | |||||||
Beta | p-Value | Beta | p-Value | Beta | p-Value | Beta | p-Value | |
Age | 0.357 | <0.001 | 0.415 | <0.001 | 0.314 | <0.001 | 0.278 | <0.001 |
Hypertension | 0.081 | 0.020 | 0.086 | <0.001 | 0.086 | <0.001 | ||
Dyslipidemia | −0.008 | 0.804 | −0.021 | 0.387 | ||||
Diabetes | 0.019 | 0.566 | 0.015 | 0.490 | ||||
Sleep time | −0.019 | 0.564 | 0.020 | 0.375 | ||||
Alcohol | 0.124 | <0.001 | 0.124 | <0.001 | 0.098 | <0.001 | 0.110 | <0.001 |
Brinkman index | 0.028 | 0.419 | 0.010 | 0.676 | ||||
METs | −0.045 | 0.160 | −0.062 | 0.005 | ||||
BMI | −0.058 | 0.349 | 0.048 | 0.340 | ||||
BFM | 0.080 | 0.381 | −0.039 | 0.608 | 0.181 | <0.001 | ||
SMM | −0.052 | 0.533 | −0.061 | 0.262 | ||||
VAT | 0.130 | 0.326 | 0.184 | <0.001 | 0.173 | 0.003 | 0.203 | <0.001 |
SAT | 0.009 | 0.936 | 0.138 | 0.016 | ||||
VAT/SAT ratio | 0.011 | 0.902 | −0.027 | 0.551 |
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Koyama, T.; Kuriyama, N.; Uehara, R. Midregional Proadrenomedullin Can Reflect the Accumulation of Visceral Adipose Tissue—A Key to Explaining the Obesity Paradox. Int. J. Environ. Res. Public Health 2020, 17, 3968. https://doi.org/10.3390/ijerph17113968
Koyama T, Kuriyama N, Uehara R. Midregional Proadrenomedullin Can Reflect the Accumulation of Visceral Adipose Tissue—A Key to Explaining the Obesity Paradox. International Journal of Environmental Research and Public Health. 2020; 17(11):3968. https://doi.org/10.3390/ijerph17113968
Chicago/Turabian StyleKoyama, Teruhide, Nagato Kuriyama, and Ritei Uehara. 2020. "Midregional Proadrenomedullin Can Reflect the Accumulation of Visceral Adipose Tissue—A Key to Explaining the Obesity Paradox" International Journal of Environmental Research and Public Health 17, no. 11: 3968. https://doi.org/10.3390/ijerph17113968