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

• Published in: International Journal of Obesity 2018-04, Vol.42 (4), p.817-825
• Main Authors: Jokinen, R, Rinnankoski-Tuikka, R, Kaye, S, Saarinen, L, Heinonen, S, Myöhänen, M, Rappou, E, Jukarainen, S, Rissanen, A, Pessia, A, Velagapudi, V, Virtanen, K A, Pirinen, E, Pietiläinen, K H
• Format: Article
• Language: English
• Subjects: 38/61; 38/77; 631/337/2019; 631/443/319/333; 692/308/575; 692/699/2743/393; 692/700/2817; 82/1; 82/29; Abnormalities; Adipose tissue; Amino acids; Body mass index; Body size; Body weight loss; Catabolism; Chain branching; Copy number; Deoxyribonucleic acid; DNA; Emission measurements; Epidemiology; Gene expression; Glucose; Health aspects; Health Promotion and Disease Prevention; Indexing; Internal Medicine; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolites; Mitochondria; Mitochondrial diseases; Mitochondrial DNA; Obesity; original-article; Oxidation; Oxidative phosphorylation; Phosphorylation; Positron emission; Positron emission tomography; Proteins; Public Health; Success; Transcription; Tricarboxylic acid cycle; Weight loss
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/ijo.2017.299

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.