Diets rich in whole grains increase betainized compounds associated with glucose metabolism

Olli Kärkkäinen, Maria A. Lankinen, Marilena Vitale, Jenna Jokkala, Jukka Leppänen, Ville Koistinen, Marko Lehtonen, Rosalba Giacco, Natalia Rosa-Sibakov, Valérie Micard, Angela A.A. Rivellese, Ursula Schwab, Hannu Mykkänen, Matti Uusitupa, Marjukka Kolehmainen, Gabriele Riccardi, Kaisa Poutanen, Seppo Auriola, Kati Hanhineva

Research output: Contribution to journalArticleScientificpeer-review

9 Citations (Scopus)

Abstract

Background: Epidemiologic evidence suggests that diets rich in whole grains are associated with a reduced risk of developing chronic diseases and all-cause mortality. However, the molecular mechanisms behind these beneficial metabolic effects are poorly understood. Objective: Our aim was to investigate novel trimethylated (betainized) compounds from mice and humans, and their association with whole grain-rich diets and insulin resistance and insulin secretion. Design: Fasting plasma samples were obtained in a mouse (C57BL/6J male) feeding trial and a controlled dietary intervention. The mouse trial involved feeding the mice a rye and wheat bran-enriched feed which was compared with a high-fat diet. In the human trial, participants recruited from Kuopio, Finland (n = 69) and Naples, Italy (n = 54) with characteristics of the metabolic syndrome were randomly assigned to either a whole grain-enriched diet or a control diet for 12 wk. Plasma concentrations of betainized compounds were analyzed with the use of liquid chromatography-tandem mass spectrometry. Insulin resistance and insulin secretion were assessed in an oral-glucose-tolerance test and a meal-glucose-tolerance test. Results: The betaines that were increased in mouse plasma after bran-enriched feeding were identified de novo via chemical synthesis and liquid chromatography-tandem mass spectrometry, and confirmed to be associated with an increased intake of whole-grain products in humans. In particular, the concentrations of pipecolic acid betaine were increased at the end of the whole-grain intervention in both the Kuopio cohort (P < 0.001) and the Naples cohort (P < 0.05), and these concentrations inversely correlated with the postprandial glucose concentration. Furthermore, the concentration of valine betaine was substantially increased during the intervention in Naples (P < 0.001) with an inverse correlation with the postprandial insulin concentration. In addition, the concentrations of other betaines, e.g., glycine betaine and proline betaine, correlated with glucose and insulin concentrations at the end of the intervention. Conclusions: Novel betainized compounds in humans are associated with diets rich in whole grains, and they improve insulin resistance and insulin secretion. These results suggest that these novel compounds may contribute to the beneficial effects of whole grain-rich diets. The studies were registered at clinicaltrials.gov as NCT00945854 (Naples) and NCT00573781 (Kuopio).

Original languageEnglish
Pages (from-to)971-979
Number of pages9
JournalThe American journal of clinical nutrition
Volume108
Issue number5
DOIs
Publication statusPublished - 1 Nov 2018
MoE publication typeNot Eligible

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Betaine
Diet
Glucose
Insulin
Insulin Resistance
Glucose Tolerance Test
Tandem Mass Spectrometry
Liquid Chromatography
Dietary Fiber
Valine
High Fat Diet
Finland
Whole Grains
Inbred C57BL Mouse
Italy
Meals
Fasting
Chronic Disease
Mortality

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Kärkkäinen, O., Lankinen, M. A., Vitale, M., Jokkala, J., Leppänen, J., Koistinen, V., ... Hanhineva, K. (2018). Diets rich in whole grains increase betainized compounds associated with glucose metabolism. The American journal of clinical nutrition, 108(5), 971-979. https://doi.org/10.1093/ajcn/nqy169
Kärkkäinen, Olli ; Lankinen, Maria A. ; Vitale, Marilena ; Jokkala, Jenna ; Leppänen, Jukka ; Koistinen, Ville ; Lehtonen, Marko ; Giacco, Rosalba ; Rosa-Sibakov, Natalia ; Micard, Valérie ; Rivellese, Angela A.A. ; Schwab, Ursula ; Mykkänen, Hannu ; Uusitupa, Matti ; Kolehmainen, Marjukka ; Riccardi, Gabriele ; Poutanen, Kaisa ; Auriola, Seppo ; Hanhineva, Kati. / Diets rich in whole grains increase betainized compounds associated with glucose metabolism. In: The American journal of clinical nutrition. 2018 ; Vol. 108, No. 5. pp. 971-979.
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title = "Diets rich in whole grains increase betainized compounds associated with glucose metabolism",
abstract = "Background: Epidemiologic evidence suggests that diets rich in whole grains are associated with a reduced risk of developing chronic diseases and all-cause mortality. However, the molecular mechanisms behind these beneficial metabolic effects are poorly understood. Objective: Our aim was to investigate novel trimethylated (betainized) compounds from mice and humans, and their association with whole grain-rich diets and insulin resistance and insulin secretion. Design: Fasting plasma samples were obtained in a mouse (C57BL/6J male) feeding trial and a controlled dietary intervention. The mouse trial involved feeding the mice a rye and wheat bran-enriched feed which was compared with a high-fat diet. In the human trial, participants recruited from Kuopio, Finland (n = 69) and Naples, Italy (n = 54) with characteristics of the metabolic syndrome were randomly assigned to either a whole grain-enriched diet or a control diet for 12 wk. Plasma concentrations of betainized compounds were analyzed with the use of liquid chromatography-tandem mass spectrometry. Insulin resistance and insulin secretion were assessed in an oral-glucose-tolerance test and a meal-glucose-tolerance test. Results: The betaines that were increased in mouse plasma after bran-enriched feeding were identified de novo via chemical synthesis and liquid chromatography-tandem mass spectrometry, and confirmed to be associated with an increased intake of whole-grain products in humans. In particular, the concentrations of pipecolic acid betaine were increased at the end of the whole-grain intervention in both the Kuopio cohort (P < 0.001) and the Naples cohort (P < 0.05), and these concentrations inversely correlated with the postprandial glucose concentration. Furthermore, the concentration of valine betaine was substantially increased during the intervention in Naples (P < 0.001) with an inverse correlation with the postprandial insulin concentration. In addition, the concentrations of other betaines, e.g., glycine betaine and proline betaine, correlated with glucose and insulin concentrations at the end of the intervention. Conclusions: Novel betainized compounds in humans are associated with diets rich in whole grains, and they improve insulin resistance and insulin secretion. These results suggest that these novel compounds may contribute to the beneficial effects of whole grain-rich diets. The studies were registered at clinicaltrials.gov as NCT00945854 (Naples) and NCT00573781 (Kuopio).",
author = "Olli K{\"a}rkk{\"a}inen and Lankinen, {Maria A.} and Marilena Vitale and Jenna Jokkala and Jukka Lepp{\"a}nen and Ville Koistinen and Marko Lehtonen and Rosalba Giacco and Natalia Rosa-Sibakov and Val{\'e}rie Micard and Rivellese, {Angela A.A.} and Ursula Schwab and Hannu Mykk{\"a}nen and Matti Uusitupa and Marjukka Kolehmainen and Gabriele Riccardi and Kaisa Poutanen and Seppo Auriola and Kati Hanhineva",
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Kärkkäinen, O, Lankinen, MA, Vitale, M, Jokkala, J, Leppänen, J, Koistinen, V, Lehtonen, M, Giacco, R, Rosa-Sibakov, N, Micard, V, Rivellese, AAA, Schwab, U, Mykkänen, H, Uusitupa, M, Kolehmainen, M, Riccardi, G, Poutanen, K, Auriola, S & Hanhineva, K 2018, 'Diets rich in whole grains increase betainized compounds associated with glucose metabolism', The American journal of clinical nutrition, vol. 108, no. 5, pp. 971-979. https://doi.org/10.1093/ajcn/nqy169

Diets rich in whole grains increase betainized compounds associated with glucose metabolism. / Kärkkäinen, Olli; Lankinen, Maria A.; Vitale, Marilena; Jokkala, Jenna; Leppänen, Jukka; Koistinen, Ville; Lehtonen, Marko; Giacco, Rosalba; Rosa-Sibakov, Natalia; Micard, Valérie; Rivellese, Angela A.A.; Schwab, Ursula; Mykkänen, Hannu; Uusitupa, Matti; Kolehmainen, Marjukka; Riccardi, Gabriele; Poutanen, Kaisa; Auriola, Seppo; Hanhineva, Kati.

In: The American journal of clinical nutrition, Vol. 108, No. 5, 01.11.2018, p. 971-979.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Diets rich in whole grains increase betainized compounds associated with glucose metabolism

AU - Kärkkäinen, Olli

AU - Lankinen, Maria A.

AU - Vitale, Marilena

AU - Jokkala, Jenna

AU - Leppänen, Jukka

AU - Koistinen, Ville

AU - Lehtonen, Marko

AU - Giacco, Rosalba

AU - Rosa-Sibakov, Natalia

AU - Micard, Valérie

AU - Rivellese, Angela A.A.

AU - Schwab, Ursula

AU - Mykkänen, Hannu

AU - Uusitupa, Matti

AU - Kolehmainen, Marjukka

AU - Riccardi, Gabriele

AU - Poutanen, Kaisa

AU - Auriola, Seppo

AU - Hanhineva, Kati

PY - 2018/11/1

Y1 - 2018/11/1

N2 - Background: Epidemiologic evidence suggests that diets rich in whole grains are associated with a reduced risk of developing chronic diseases and all-cause mortality. However, the molecular mechanisms behind these beneficial metabolic effects are poorly understood. Objective: Our aim was to investigate novel trimethylated (betainized) compounds from mice and humans, and their association with whole grain-rich diets and insulin resistance and insulin secretion. Design: Fasting plasma samples were obtained in a mouse (C57BL/6J male) feeding trial and a controlled dietary intervention. The mouse trial involved feeding the mice a rye and wheat bran-enriched feed which was compared with a high-fat diet. In the human trial, participants recruited from Kuopio, Finland (n = 69) and Naples, Italy (n = 54) with characteristics of the metabolic syndrome were randomly assigned to either a whole grain-enriched diet or a control diet for 12 wk. Plasma concentrations of betainized compounds were analyzed with the use of liquid chromatography-tandem mass spectrometry. Insulin resistance and insulin secretion were assessed in an oral-glucose-tolerance test and a meal-glucose-tolerance test. Results: The betaines that were increased in mouse plasma after bran-enriched feeding were identified de novo via chemical synthesis and liquid chromatography-tandem mass spectrometry, and confirmed to be associated with an increased intake of whole-grain products in humans. In particular, the concentrations of pipecolic acid betaine were increased at the end of the whole-grain intervention in both the Kuopio cohort (P < 0.001) and the Naples cohort (P < 0.05), and these concentrations inversely correlated with the postprandial glucose concentration. Furthermore, the concentration of valine betaine was substantially increased during the intervention in Naples (P < 0.001) with an inverse correlation with the postprandial insulin concentration. In addition, the concentrations of other betaines, e.g., glycine betaine and proline betaine, correlated with glucose and insulin concentrations at the end of the intervention. Conclusions: Novel betainized compounds in humans are associated with diets rich in whole grains, and they improve insulin resistance and insulin secretion. These results suggest that these novel compounds may contribute to the beneficial effects of whole grain-rich diets. The studies were registered at clinicaltrials.gov as NCT00945854 (Naples) and NCT00573781 (Kuopio).

AB - Background: Epidemiologic evidence suggests that diets rich in whole grains are associated with a reduced risk of developing chronic diseases and all-cause mortality. However, the molecular mechanisms behind these beneficial metabolic effects are poorly understood. Objective: Our aim was to investigate novel trimethylated (betainized) compounds from mice and humans, and their association with whole grain-rich diets and insulin resistance and insulin secretion. Design: Fasting plasma samples were obtained in a mouse (C57BL/6J male) feeding trial and a controlled dietary intervention. The mouse trial involved feeding the mice a rye and wheat bran-enriched feed which was compared with a high-fat diet. In the human trial, participants recruited from Kuopio, Finland (n = 69) and Naples, Italy (n = 54) with characteristics of the metabolic syndrome were randomly assigned to either a whole grain-enriched diet or a control diet for 12 wk. Plasma concentrations of betainized compounds were analyzed with the use of liquid chromatography-tandem mass spectrometry. Insulin resistance and insulin secretion were assessed in an oral-glucose-tolerance test and a meal-glucose-tolerance test. Results: The betaines that were increased in mouse plasma after bran-enriched feeding were identified de novo via chemical synthesis and liquid chromatography-tandem mass spectrometry, and confirmed to be associated with an increased intake of whole-grain products in humans. In particular, the concentrations of pipecolic acid betaine were increased at the end of the whole-grain intervention in both the Kuopio cohort (P < 0.001) and the Naples cohort (P < 0.05), and these concentrations inversely correlated with the postprandial glucose concentration. Furthermore, the concentration of valine betaine was substantially increased during the intervention in Naples (P < 0.001) with an inverse correlation with the postprandial insulin concentration. In addition, the concentrations of other betaines, e.g., glycine betaine and proline betaine, correlated with glucose and insulin concentrations at the end of the intervention. Conclusions: Novel betainized compounds in humans are associated with diets rich in whole grains, and they improve insulin resistance and insulin secretion. These results suggest that these novel compounds may contribute to the beneficial effects of whole grain-rich diets. The studies were registered at clinicaltrials.gov as NCT00945854 (Naples) and NCT00573781 (Kuopio).

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JO - The American journal of clinical nutrition

JF - The American journal of clinical nutrition

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Kärkkäinen O, Lankinen MA, Vitale M, Jokkala J, Leppänen J, Koistinen V et al. Diets rich in whole grains increase betainized compounds associated with glucose metabolism. The American journal of clinical nutrition. 2018 Nov 1;108(5):971-979. https://doi.org/10.1093/ajcn/nqy169