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Plasma metabolomic response to postmenopausal weight loss induced by different diets

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Abstract

Background

Menopause is associated with increased abdominal fat and increased risk of developing diabetes and cardiovascular disease.

Objectives

The present study evaluated the plasma metabolic response in relation to insulin sensitivity after weight loss via diet intervention.

Methods

This work includes two studies; i) Ten women on a 5 weeks Paleolithic-type diet (PD, 30 energy percent (E%) protein, 40 E% fat, 30 E% carbohydrates), ii) 55 women on 6 months of either PD or Nordic Nutrition Recommendations diet (NNR, 15 E% protein, 30 E% fat, and 55 E% carbohydrates). Plasma metabolic profiles were acquired at baseline and post diet using gas chromatography time-of-flight/mass spectrometry and investigated in relation to insulin sensitivity using multivariate bioinformatics.

Results

Both the PD and NNR diet resulted in significant weight loss, reduced waist circumference, improved serum lipid profiles, and improved insulin sensitivity. We detected a baseline metabolic profile that correlated significantly with insulin sensitivity, and of which components increased significantly in the PD group compared to NNR. Specifically, a significant increase in myo-inositol (MI), a second messenger of insulin action, and β-hydroxybutyric acid (β-HB) increased while dihomo-gamma-linoleic acid (DGLA) decreased in PD compared to NNR, which correlated with improved insulin sensitivity. We also detected a significant decrease in tyrosine and tryptophan, potential markers of insulin resistance when elevated in the circulation, with the PD but not the NNR.

Conclusions

Using metabolomics, we detected changes in the plasma metabolite profiles associated with weight loss in postmenopausal women by different diets. The metabolic profiles following 6 months of PD were linked to beneficial effects on insulin sensitivity compared to NNR.

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References

  • Becker, W. (2005). New Nordic nutrition recommendations 2004. Physical activity as important as good nourishing food. Lakartidningen, 102, 2757-8–2760-2.

    Google Scholar 

  • Brennan, L. (2013). Metabolomics in nutrition research: Current status and perspectives. Biochemical Society Transactions, 41, 670–673.

    Article  CAS  PubMed  Google Scholar 

  • Clements, R. S., & Darnell, B. (1980). Myoinositol content of common foods—development of a high-myo-inositol diet. American Journal of Clinical Nutrition, 33, 1954–1967.

    CAS  PubMed  Google Scholar 

  • Corrado, F., D’Anna, R., Di Vieste, G., Giordano, D., Pintaudi, B., Santamaria, A., & Di Benedetto, A. (2011). The effect of myoinositol supplementation on insulin resistance in patients with gestational diabetes. Diabetic Medicine, 28(8), 972–975.

    Article  CAS  PubMed  Google Scholar 

  • Dunaif, A. (1997). Insulin resistance and the polycystic ovary syndrome: Mechanism and implications for pathogenesis. Endocrine Reviews, 18, 774–800.

    CAS  PubMed  Google Scholar 

  • EFRON, B. A. G., G. 1983. A Leisurely Look at the Bootstrap, the Jack-knife, and Cross-validation. The American Statistician. http://www.jstor.org/stable/2685844: American Statistical Association.

  • Fiehn, O., Kopka, J., Dormann, P., Altmann, T., Trethewey, R. N., & Willmitzer, L. (2000). Metabolite profiling for plant functional genomics. Nature Biotechnology, 18, 1157–1161.

    Article  CAS  PubMed  Google Scholar 

  • Genazzani, A. D., Lanzoni, C., Ricchieri, F., & Jasonni, V. M. (2008). Myo-inositol administration positively affects hyperinsulinemia and hormonal parameters in overweight patients with polycystic ovary syndrome. Gynecological Endocrinology, 24, 139–144.

    Article  CAS  PubMed  Google Scholar 

  • Giordano, D., Corrado, F., Santamaria, A., Quattrone, S., Pintaudi, B., di Benedetto, A., & D’Anna, R. (2011). Effects of myo-inositol supplementation in postmenopausal women with metabolic syndrome: A perspective, randomized, placebo-controlled study. Menopause-the Journal of the North American Menopause Society, 18, 102–104.

    Article  Google Scholar 

  • Jönsson, T., Granfeldt, Y., Ahrén, B., Branell, U. C., Pålsson, G., Hansson, A., et al. (2009). Beneficial effects of a Paleolithic diet on cardiovascular risk factors in type 2 diabetes: A randomized cross-over pilot study. Cardiovasc Diabetol, 8(35), 1–14.

    Google Scholar 

  • Jönsson, T., Granfeldt, Y., Erlanson-Albertsson, C., Ahrén, B., & Lindeberg, S. (2010). A paleolithic diet is more satiating per calorie than a mediterranean-like diet in individuals with ischemic heart disease. Nutrition & metabolism, 7(1), 1.

    Article  Google Scholar 

  • Jonsson, P., Johansson, A. I., Gullberg, J., Trygg, J., Grung, B., Marklund, S., et al. (2005). High-throughput data analysis for detecting and identifying differences between samples in GC/MS-based metabolomic analyses. Analytical Chemistry, 77(17), 5635–5642.

    Article  CAS  PubMed  Google Scholar 

  • Jonsson, P., Johansson, E. S., Wuolikainen, A., Lindberg, J., Schuppe-Koistinen, I., Kusano, M., et al. (2006). Predictive metabolite profiling applying hierarchical multivariate curve resolution to GC-MS datas - A potential tool for multi-parametric diagnosis. Journal of Proteome Research, 5, 1407–1414.

    Article  CAS  PubMed  Google Scholar 

  • Kapoor, R., & Huang, Y.-S. (2006). Gamma linolenic acid: An antiinflammatory omega-6 fatty acid. Current Pharmaceutical Biotechnology, 7, 531–534.

    Article  CAS  PubMed  Google Scholar 

  • Kell, D. B. (2004). Metabolomics and systems biology: Making sense of the soup. Current Opinion in Microbiology, 7, 296–307.

    Article  CAS  PubMed  Google Scholar 

  • Lemieux, M., Al-Jawadi, A., Wang, S., & Moustaid-Moussa, N. (2013). Metabolic Profiling in Nutrition and Metabolic Disorders. Advances in Nutrition, 4, 548–550.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lindeberg, S., Jonsson, T., Granfeldt, Y., Borgstrand, E., Soffman, J., Sjostrom, K., & Ahren, B. (2007). A Palaeolithic diet improves glucose tolerance more than a Mediterranean-like diet in individuals with ischaemic heart disease. Diabetologia, 50, 1795–1807.

    Article  CAS  PubMed  Google Scholar 

  • Lisabeth, L. D., Beiser, A. S., Brown, D. L., Murabito, J. M., Kelly-Hayes, M., & Wolf, P. A. (2009). Age at natural menopause and risk of ischemic stroke The Framingham Heart Study. Stroke, 40, 1044–1049.

    Article  PubMed  PubMed Central  Google Scholar 

  • McNiven, E. M. S., German, J. B., & Slupsky, C. M. (2011). Analytical metabolomics: Nutritional opportunities for personalized health. Journal of Nutritional Biochemistry, 22, 995–1002.

    Article  CAS  PubMed  Google Scholar 

  • Mellberg, C., Sandberg, S., Ryberg, M., Eriksson, M., Brage, S., Larsson, C., et al. (2014). Long-term effects of a Palaeolithic-type diet in obese postmenopausal women: A 2-year randomized trial. European Journal of Clinical Nutrition, 68, 350–357.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nestler, J. E., Jakubowicz, D. J., Reamer, P., Gunn, R. D., & Allan, G. (1999). Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. New England Journal of Medicine, 340, 1314–1320.

    Article  CAS  PubMed  Google Scholar 

  • Newgard, C. B., An, J., Bain, J. R., Muehlbauer, M. J., Stevens, R. D., Lien, L. F., et al. (2009). A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metabolism, 9(4), 311–326.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Peppa, M., Koliaki, C., Papaefstathiou, A., Garoflos, E., Katsilambros, N., Raptis, S. A., et al. (2013). Body composition determinants of metabolic phenotypes of obesity in nonobese and obese postmenopausal women. Obesity, 21, 1807–1814.

    PubMed  Google Scholar 

  • Redestig, H., Fukushima, A., Stenlund, H., Moritz, T., Arita, M., Saito, K., & Kusano, M. (2009). Compensation for systematic cross-contribution improves normalization of mass spectrometry based metabolomics data. Analytical Chemistry, 81, 7974–7980.

    Article  CAS  PubMed  Google Scholar 

  • Ren, J., & Ceylan-Isik, A. F. (2004). Diabetic cardiomyopathy—Do women differ from men? Endocrine, 25, 73–83.

    Article  CAS  PubMed  Google Scholar 

  • Rexrode, K. M., Carey, V. J., Hennekens, C. H., Walters, E. E., Colditz, G. A., Stampfer, M. J., et al. (1998). Abdominal adiposity and coronary heart disease in women. Jama-Journal of the American Medical Association, 280, 1843–1848.

    Article  CAS  Google Scholar 

  • Russo, G. L. (2009). Dietary n-6 and n-3 polyunsaturated fatty acids: From biochemistry to clinical implications in cardiovascular prevention. Biochemical Pharmacology, 77, 937–946.

    Article  CAS  PubMed  Google Scholar 

  • Ryberg, M., Sandberg, S., Mellberg, C., Stegle, O., Lindahl, B., Larsson, C., et al. (2013). A Palaeolithic-type diet causes strong tissue-specific effects on ectopic fat deposition in obese postmenopausal women. Journal of Internal Medicine, 274, 67–76.

    Article  CAS  PubMed  Google Scholar 

  • Sakuma, M., Kametani, S., & Akanuma, H. (1998). Purification and some properties of a hepatic NADPH-dependent reductase that specifically acts on 1,5-anhydro-D-fructose. Journal of Biochemistry, 123, 189–193.

    Article  CAS  PubMed  Google Scholar 

  • Saltiel, A. R., & Kahn, C. R. (2001). Insulin signalling and the regulation of glucose and lipid metabolism. Nature, 414, 799–806.

    Article  CAS  PubMed  Google Scholar 

  • Suhre, K. (2014). Metabolic profiling in diabetes. Journal of Endocrinology, 221, R75–R85.

    Article  CAS  PubMed  Google Scholar 

  • Trygg, J., Gullberg, J., Johansson, A. I., Jonsson, P., Antti, H., Marklund, S. L., & Moritz, T. (2005). Extraction and GC/MS analysis of the human blood plasma metabolome. Analytical Chemistry, 77, 8086–8094.

    Article  PubMed  Google Scholar 

  • Virtanen, J. K., Mursu, J., Voutilainen, S., Uusitupa, M., & Tuomainen, T.-P. (2014). Serum omega-3 polyunsaturated fatty acids and risk of incident type 2 diabetes in men: The Kuopio Ischemic Heart Disease Risk Factor study. Diabetes Care, 37, 189–196.

    Article  CAS  PubMed  Google Scholar 

  • Wang, T. J., Larson, M. G., Vasan, R. S., Cheng, S., Rhee, E. P., McCabe, E., et al. (2011). Metabolite profiles and the risk of developing diabetes. Nature Medicine, 17, 448–453.

    Article  PubMed  PubMed Central  Google Scholar 

  • Wishart, D. S., Tzur, D., Knox, C., Eisner, R., Guo, A. C., Young, N., et al. (2007). HMDB: The human metabolome database. Nucleic Acids Research, 35, D521–D526.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamanouchi, T., Inoue, T., Ichiyanagi, K., Sakai, T., & Ogata, N. (2003). 1,5-Anhydroglucitol stimulates insulin release in insulinoma cell lines. Biochimica Et Biophysica Acta-General Subjects, 1623, 82–87.

    Article  CAS  Google Scholar 

  • Yamanouchi, T., Ogata, N., Tagaya, T., Kawasaki, T., Sekino, N., Funato, H., et al. (1996). Clinical usefulness of serum 1,5-anhydroglucitol in monitoring glycaemic control. Lancet, 347, 1514–1518.

    Article  CAS  PubMed  Google Scholar 

  • Zeisel, S. H., Freake, H. C., Bauman, D. E., Bier, D. M., Burrin, D. G., German, J. B., et al. (2005). The nutritional phenotype in the age of metabolomics. Journal of Nutrition, 135, 1613–1616.

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

We are grateful to all of the women who participated in this study. Krister Lundgren and Inga-Britt Carlsson assisted during the GC-TOF/MS analysis, and Inger Arnesjö made important contributions during the dietary intervention studies. This work was supported by grants from the Swedish Research Council (VR), the Swedish Council for Working Life and Social Research, the Swedish Strategic Research Foundation (SSF), Wallenberg Consortium North (WCN), the Kempe Foundation, the Swedish Heart and Lung Foundation, the Medical Faculty at Umeå University, and the Västerbotten County Council.

Financial support

This study was supported by grants from The Swedish Council for Working Life and Social Research (2006-0699 and 2010-0398), the Swedish Research Council (K2011-12237-15-6), the Swedish Heart and Lung Foundation, the Swedish Diabetes Foundation, King Gustaf V and Drottning Victorias Foundation, the County Council of Västerbotten, and Umeå University, Sweden.

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Correspondence to Elin Chorell.

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Henrik Antti and Tommy Olsson have shared senior authorship.

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Chorell, E., Ryberg, M., Larsson, C. et al. Plasma metabolomic response to postmenopausal weight loss induced by different diets. Metabolomics 12, 85 (2016). https://doi.org/10.1007/s11306-016-1013-x

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