Characterising metabolically healthy obesity in weight-discordant monozygotic twins

J Naukkarinen; S Heinonen; A Hakkarainen; J Lundbom; K Vuolteenaho; L Saarinen; S Hautaniemi; A Rodriguez; G Frühbeck; P Pajunen; Tuulia Hyötyläinen; Matej Oresic; E Moilanen; A Suomalainen; N Lundbom; J Kaprio; A Rissanen; K H Pietiläinen

doi:10.1007/s00125-013-3066-y

Characterising metabolically healthy obesity in weight-discordant monozygotic twins

J Naukkarinen, S Heinonen, A Hakkarainen, J Lundbom, K Vuolteenaho, L Saarinen, S Hautaniemi, A Rodriguez, G Frühbeck, P Pajunen, Tuulia Hyötyläinen, Matej Oresic, E Moilanen, A Suomalainen, N Lundbom, J Kaprio, A Rissanen, K H Pietiläinen (Corresponding Author)

VTT Technical Research Centre of Finland

Research output: Contribution to journal › Article › Scientific › peer-review

90 Citations (Scopus)

Abstract

Aims/hypothesis: Not all obese individuals display the metabolic disturbances commonly associated with excess fat accumulation. Mechanisms maintaining this 'metabolically healthy obesity' (MHO) are as yet unknown. We aimed to study different fat depots and transcriptional pathways in subcutaneous adipose tissue (SAT) as related to the MHO phenomenon. Methods: Sixteen rare young adult obesity-discordant monozygotic (MZ) twin pairs (intra-pair difference (â^+) in BMI =3 kg/m2), aged 22.8-35.8 years, were examined for detailed characteristics of metabolic health (subcutaneous, intra-abdominal and liver fat [magnetic resonance imaging/spectroscopy]), OGTT, lipids, adipokines and C-reactive protein (CRP). Affymetrix U133 Plus 2.0 chips were used to analyse transcriptomics pathways related to mitochondrial function and inflammation in SAT. Results: Based on liver fat accumulation, two metabolically different subgroups emerged. In half (8/16) of the pairs (â^+weight 17.1 ± 2.0 kg), the obese co-twin had significantly higher liver fat (â^+718%), 78% increase in AUC insulin during OGTT and CRP, significantly more disturbance in the lipid profile and greater tendency for hypertension compared with the lean co-twin. In these obese co-twins, SAT expression of mitochondrial oxidative phosphorylation, branched-chain amino acid catabolism, fatty acid oxidation and adipocyte differentiation pathways were downregulated and chronic inflammation upregulated. In the other eight pairs (â^+weight 17.4 ± 2.8 kg), the obese co-twin did not differ from the non-obese co-twin in liver fat (â^+8%), insulin sensitivity, CRP, lipids, blood pressure or SAT transcriptomics. Conclusions/interpretation: Our results suggest that maintenance of high mitochondrial transcription and lack of inflammation in SAT are associated with low liver fat and MHO

Original language	English
Pages (from-to)	167-176
Journal	Diabetologia
Volume	57
Issue number	1
DOIs	https://doi.org/10.1007/s00125-013-3066-y
Publication status	Published - 2014
MoE publication type	A1 Journal article-refereed

Keywords

Adipose tissue
diabetes
fatty liver
inflammation
metabolically healthy obesy
obesity

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Naukkarinen, J., Heinonen, S., Hakkarainen, A., Lundbom, J., Vuolteenaho, K., Saarinen, L., Hautaniemi, S., Rodriguez, A., Frühbeck, G., Pajunen, P., Hyötyläinen, T., Oresic, M., Moilanen, E., Suomalainen, A., Lundbom, N., Kaprio, J., Rissanen, A., & Pietiläinen, K. H. (2014). Characterising metabolically healthy obesity in weight-discordant monozygotic twins. Diabetologia, 57(1), 167-176. https://doi.org/10.1007/s00125-013-3066-y

Naukkarinen, J ; Heinonen, S ; Hakkarainen, A ; Lundbom, J ; Vuolteenaho, K ; Saarinen, L ; Hautaniemi, S ; Rodriguez, A ; Frühbeck, G ; Pajunen, P ; Hyötyläinen, Tuulia ; Oresic, Matej ; Moilanen, E ; Suomalainen, A ; Lundbom, N ; Kaprio, J ; Rissanen, A ; Pietiläinen, K H. / Characterising metabolically healthy obesity in weight-discordant monozygotic twins. In: Diabetologia. 2014 ; Vol. 57, No. 1. pp. 167-176.

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title = "Characterising metabolically healthy obesity in weight-discordant monozygotic twins",

abstract = "Aims/hypothesis: Not all obese individuals display the metabolic disturbances commonly associated with excess fat accumulation. Mechanisms maintaining this 'metabolically healthy obesity' (MHO) are as yet unknown. We aimed to study different fat depots and transcriptional pathways in subcutaneous adipose tissue (SAT) as related to the MHO phenomenon. Methods: Sixteen rare young adult obesity-discordant monozygotic (MZ) twin pairs (intra-pair difference ({\^a}^+) in BMI =3 kg/m2), aged 22.8-35.8 years, were examined for detailed characteristics of metabolic health (subcutaneous, intra-abdominal and liver fat [magnetic resonance imaging/spectroscopy]), OGTT, lipids, adipokines and C-reactive protein (CRP). Affymetrix U133 Plus 2.0 chips were used to analyse transcriptomics pathways related to mitochondrial function and inflammation in SAT. Results: Based on liver fat accumulation, two metabolically different subgroups emerged. In half (8/16) of the pairs ({\^a}^+weight 17.1 ± 2.0 kg), the obese co-twin had significantly higher liver fat ({\^a}^+718%), 78% increase in AUC insulin during OGTT and CRP, significantly more disturbance in the lipid profile and greater tendency for hypertension compared with the lean co-twin. In these obese co-twins, SAT expression of mitochondrial oxidative phosphorylation, branched-chain amino acid catabolism, fatty acid oxidation and adipocyte differentiation pathways were downregulated and chronic inflammation upregulated. In the other eight pairs ({\^a}^+weight 17.4 ± 2.8 kg), the obese co-twin did not differ from the non-obese co-twin in liver fat ({\^a}^+8%), insulin sensitivity, CRP, lipids, blood pressure or SAT transcriptomics. Conclusions/interpretation: Our results suggest that maintenance of high mitochondrial transcription and lack of inflammation in SAT are associated with low liver fat and MHO",

keywords = "Adipose tissue, diabetes, fatty liver, inflammation, metabolically healthy obesy, obesity",

author = "J Naukkarinen and S Heinonen and A Hakkarainen and J Lundbom and K Vuolteenaho and L Saarinen and S Hautaniemi and A Rodriguez and G Fr{\"u}hbeck and P Pajunen and Tuulia Hy{\"o}tyl{\"a}inen and Matej Oresic and E Moilanen and A Suomalainen and N Lundbom and J Kaprio and A Rissanen and Pietil{\"a}inen, {K H}",

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Naukkarinen, J, Heinonen, S, Hakkarainen, A, Lundbom, J, Vuolteenaho, K, Saarinen, L, Hautaniemi, S, Rodriguez, A, Frühbeck, G, Pajunen, P, Hyötyläinen, T, Oresic, M, Moilanen, E, Suomalainen, A, Lundbom, N, Kaprio, J, Rissanen, A & Pietiläinen, KH 2014, 'Characterising metabolically healthy obesity in weight-discordant monozygotic twins', Diabetologia, vol. 57, no. 1, pp. 167-176. https://doi.org/10.1007/s00125-013-3066-y

Characterising metabolically healthy obesity in weight-discordant monozygotic twins. / Naukkarinen, J; Heinonen, S; Hakkarainen, A; Lundbom, J; Vuolteenaho, K; Saarinen, L; Hautaniemi, S; Rodriguez, A; Frühbeck, G; Pajunen, P; Hyötyläinen, Tuulia; Oresic, Matej; Moilanen, E; Suomalainen, A; Lundbom, N; Kaprio, J; Rissanen, A; Pietiläinen, K H (Corresponding Author).

In: Diabetologia, Vol. 57, No. 1, 2014, p. 167-176.

Research output: Contribution to journal › Article › Scientific › peer-review

TY - JOUR

T1 - Characterising metabolically healthy obesity in weight-discordant monozygotic twins

AU - Naukkarinen, J

AU - Heinonen, S

AU - Hakkarainen, A

AU - Lundbom, J

AU - Vuolteenaho, K

AU - Saarinen, L

AU - Hautaniemi, S

AU - Rodriguez, A

AU - Frühbeck, G

AU - Pajunen, P

AU - Hyötyläinen, Tuulia

AU - Oresic, Matej

AU - Moilanen, E

AU - Suomalainen, A

AU - Lundbom, N

AU - Kaprio, J

AU - Rissanen, A

AU - Pietiläinen, K H

PY - 2014

Y1 - 2014

N2 - Aims/hypothesis: Not all obese individuals display the metabolic disturbances commonly associated with excess fat accumulation. Mechanisms maintaining this 'metabolically healthy obesity' (MHO) are as yet unknown. We aimed to study different fat depots and transcriptional pathways in subcutaneous adipose tissue (SAT) as related to the MHO phenomenon. Methods: Sixteen rare young adult obesity-discordant monozygotic (MZ) twin pairs (intra-pair difference (â^+) in BMI =3 kg/m2), aged 22.8-35.8 years, were examined for detailed characteristics of metabolic health (subcutaneous, intra-abdominal and liver fat [magnetic resonance imaging/spectroscopy]), OGTT, lipids, adipokines and C-reactive protein (CRP). Affymetrix U133 Plus 2.0 chips were used to analyse transcriptomics pathways related to mitochondrial function and inflammation in SAT. Results: Based on liver fat accumulation, two metabolically different subgroups emerged. In half (8/16) of the pairs (â^+weight 17.1 ± 2.0 kg), the obese co-twin had significantly higher liver fat (â^+718%), 78% increase in AUC insulin during OGTT and CRP, significantly more disturbance in the lipid profile and greater tendency for hypertension compared with the lean co-twin. In these obese co-twins, SAT expression of mitochondrial oxidative phosphorylation, branched-chain amino acid catabolism, fatty acid oxidation and adipocyte differentiation pathways were downregulated and chronic inflammation upregulated. In the other eight pairs (â^+weight 17.4 ± 2.8 kg), the obese co-twin did not differ from the non-obese co-twin in liver fat (â^+8%), insulin sensitivity, CRP, lipids, blood pressure or SAT transcriptomics. Conclusions/interpretation: Our results suggest that maintenance of high mitochondrial transcription and lack of inflammation in SAT are associated with low liver fat and MHO

AB - Aims/hypothesis: Not all obese individuals display the metabolic disturbances commonly associated with excess fat accumulation. Mechanisms maintaining this 'metabolically healthy obesity' (MHO) are as yet unknown. We aimed to study different fat depots and transcriptional pathways in subcutaneous adipose tissue (SAT) as related to the MHO phenomenon. Methods: Sixteen rare young adult obesity-discordant monozygotic (MZ) twin pairs (intra-pair difference (â^+) in BMI =3 kg/m2), aged 22.8-35.8 years, were examined for detailed characteristics of metabolic health (subcutaneous, intra-abdominal and liver fat [magnetic resonance imaging/spectroscopy]), OGTT, lipids, adipokines and C-reactive protein (CRP). Affymetrix U133 Plus 2.0 chips were used to analyse transcriptomics pathways related to mitochondrial function and inflammation in SAT. Results: Based on liver fat accumulation, two metabolically different subgroups emerged. In half (8/16) of the pairs (â^+weight 17.1 ± 2.0 kg), the obese co-twin had significantly higher liver fat (â^+718%), 78% increase in AUC insulin during OGTT and CRP, significantly more disturbance in the lipid profile and greater tendency for hypertension compared with the lean co-twin. In these obese co-twins, SAT expression of mitochondrial oxidative phosphorylation, branched-chain amino acid catabolism, fatty acid oxidation and adipocyte differentiation pathways were downregulated and chronic inflammation upregulated. In the other eight pairs (â^+weight 17.4 ± 2.8 kg), the obese co-twin did not differ from the non-obese co-twin in liver fat (â^+8%), insulin sensitivity, CRP, lipids, blood pressure or SAT transcriptomics. Conclusions/interpretation: Our results suggest that maintenance of high mitochondrial transcription and lack of inflammation in SAT are associated with low liver fat and MHO

KW - Adipose tissue

KW - diabetes

KW - fatty liver

KW - inflammation

KW - metabolically healthy obesy

KW - obesity

U2 - 10.1007/s00125-013-3066-y

DO - 10.1007/s00125-013-3066-y

M3 - Article

VL - 57

SP - 167

EP - 176

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 1

ER -