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 (∆) in BMI ≥ 3 kg/m(2)), 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 (∆weight 17.1 ± 2.0 kg), the obese co-twin had significantly higher liver fat (∆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 (∆weight 17.4 ± 2.8 kg), the obese co-twin did not differ from the non-obese co-twin in liver fat (∆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.
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Authors | J Naukkarinen, S Heinonen, A Hakkarainen, J Lundbom, K Vuolteenaho, L Saarinen, S Hautaniemi, A Rodriguez, G Frühbeck, P Pajunen, T Hyötyläinen, M Orešič, E Moilanen, A Suomalainen, N Lundbom, J Kaprio, A Rissanen, K H Pietiläinen |
Journal | Diabetologia
(Diabetologia)
Vol. 57
Issue 1
Pg. 167-76
(Jan 2014)
ISSN: 1432-0428 [Electronic] Germany |
PMID | 24100782
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Topics |
- Adipose Tissue
(metabolism)
- Adult
- Body Weight
(physiology)
- Female
- Glucose Tolerance Test
- Humans
- Male
- Obesity
(blood, metabolism)
- Twins, Monozygotic
- Young Adult
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