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Int J Obes (Lond). 2018 Apr;42(4):817-825. doi: 10.1038/ijo.2017.299. Epub 2017 Dec 5.

Adipose tissue mitochondrial capacity associates with long-term weight loss success.

Author information

1
Obesity Research Unit, Research Programs Unit, Diabetes and Obesity, University of Helsinki, Biomedicum Helsinki, Helsinki, Finland.
2
Research Programs Unit, Molecular Neurology, University of Helsinki, Biomedicum Helsinki, Helsinki, Finland.
3
Research Programs Unit, Genome-Scale Biology, University of Helsinki, Biomedicum Helsinki, Helsinki, Finland.
4
Department of Psychiatry, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland.
5
Metabolomics Unit, Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland.
6
Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland.
7
Endocrinology, Abdominal Center, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland.

Abstract

OBJECTIVES:

We investigated whether (1) subcutaneous adipose tissue (SAT) mitochondrial capacity predicts weight loss success and (2) weight loss ameliorates obesity-related SAT mitochondrial abnormalities.

METHODS:

SAT biopsies were obtained from 19 clinically healthy obese subjects (body mass index (BMI) 34.6±2.7 kg m-2) during a weight loss intervention (0, 5 and 12 months) and from 19 lean reference subjects (BMI 22.7±1.1 kg m-2) at baseline. Based on 1-year weight loss outcome, the subjects were divided into two groups: continuous weight losers (WL, n=6) and weight regainers (WR, n=13). Main outcome measures included SAT mitochondrial pathways from transcriptomics, mitochondrial amount (mitochondrial DNA (mtDNA), Porin protein levels), mtDNA-encoded transcripts, oxidative phosphorylation (OXPHOS) proteins, and plasma metabolites of the mitochondrial branched-chain amino-acid catabolism (BCAA) pathway. SAT and visceral adipose tissue (VAT) glucose uptake was measured with positron emission tomography.

RESULTS:

Despite similar baseline clinical characteristics, SAT in the WL group exhibited higher gene expression level of nuclear-encoded mitochondrial pathways (P=0.0224 OXPHOS, P=0.0086 tricarboxylic acid cycle, P=0.0074 fatty acid beta-oxidation and P=0.0122 BCAA), mtDNA transcript COX1 (P=0.0229) and protein level of Porin (P=0.0462) than the WR group. Many baseline mitochondrial parameters correlated with WL success, and with SAT and VAT glucose uptake. During WL, the nuclear-encoded mitochondrial pathways were downregulated, together with increased plasma metabolite levels of BCAAs in both groups. MtDNA copy number increased in the WR group at 5 months (P=0.012), but decreased to baseline level between 5 and 12 months (P=0.015). The only significant change in the WL group for mtDNA was a reduction between 5 and 12 months (P=0.004). The levels of Porin did not change in either group upon WL.

CONCLUSIONS:

Higher mitochondrial capacity in SAT predicts good long-term WL success. WL does not ameliorate SAT mitochondrial downregulation and based on pathway expression, may paradoxically further reduce it.Data availability:The transcriptomics data generated in this study have been deposited to the Gene Expression Omnibus public repository, accession number GSE103769.

PMID:
29203860
DOI:
10.1038/ijo.2017.299
[Indexed for MEDLINE]

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