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.
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.
Authors: Rachel P Wildman; Paul Muntner; Kristi Reynolds; Aileen P McGinn; Swapnil Rajpathak; Judith Wylie-Rosett; MaryFran R Sowers Journal: Arch Intern Med Date: 2008-08-11
Authors: Elisa Fabbrini; Faidon Magkos; B Selma Mohammed; Terri Pietka; Nada A Abumrad; Bruce W Patterson; Adewole Okunade; Samuel Klein Journal: Proc Natl Acad Sci U S A Date: 2009-08-24 Impact factor: 11.205
Authors: Siobhán E McQuaid; Leanne Hodson; Matthew J Neville; A Louise Dennis; Jane Cheeseman; Sandy M Humphreys; Toralph Ruge; Marjorie Gilbert; Barbara A Fielding; Keith N Frayn; Fredrik Karpe Journal: Diabetes Date: 2010-10-13 Impact factor: 9.461
Authors: Kirsi H Pietiläinen; Jussi Naukkarinen; Aila Rissanen; Juha Saharinen; Pekka Ellonen; Heli Keränen; Anu Suomalainen; Alexandra Götz; Tapani Suortti; Hannele Yki-Järvinen; Matej Oresic; Jaakko Kaprio; Leena Peltonen Journal: PLoS Med Date: 2008-03-11 Impact factor: 11.069
Authors: M Muniandy; S Heinonen; H Yki-Järvinen; A Hakkarainen; J Lundbom; N Lundbom; J Kaprio; A Rissanen; M Ollikainen; K H Pietiläinen Journal: Int J Obes (Lond) Date: 2017-04-25 Impact factor: 5.095
Authors: R Jokinen; R Rinnankoski-Tuikka; S Kaye; L Saarinen; S Heinonen; M Myöhänen; E Rappou; S Jukarainen; A Rissanen; A Pessia; V Velagapudi; K A Virtanen; E Pirinen; K H Pietiläinen Journal: Int J Obes (Lond) Date: 2017-12-05 Impact factor: 5.095
Authors: Harish Dharuri; Peter A C 't Hoen; Jan B van Klinken; Peter Henneman; Jeroen F J Laros; Mirjam A Lips; Fatiha El Bouazzaoui; Gert-Jan B van Ommen; Ignace Janssen; Bert van Ramshorst; Bert A van Wagensveld; Hanno Pijl; Ko Willems van Dijk; Vanessa van Harmelen Journal: Diabetologia Date: 2014-08-07 Impact factor: 10.122
Authors: K H Pietiläinen; K Ismail; E Järvinen; S Heinonen; M Tummers; S Bollepalli; R Lyle; M Muniandy; E Moilanen; A Hakkarainen; J Lundbom; N Lundbom; A Rissanen; J Kaprio; M Ollikainen Journal: Int J Obes (Lond) Date: 2015-10-26 Impact factor: 5.095
Authors: S Heinonen; L Saarinen; J Naukkarinen; A Rodríguez; G Frühbeck; A Hakkarainen; J Lundbom; N Lundbom; K Vuolteenaho; E Moilanen; P Arner; S Hautaniemi; A Suomalainen; J Kaprio; A Rissanen; K H Pietiläinen Journal: Int J Obes (Lond) Date: 2014-02-19 Impact factor: 5.095
Authors: D Samocha-Bonet; V D Dixit; C R Kahn; R L Leibel; X Lin; M Nieuwdorp; K H Pietiläinen; R Rabasa-Lhoret; M Roden; P E Scherer; S Klein; E Ravussin Journal: Obes Rev Date: 2014-07-25 Impact factor: 9.213