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 -