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

: Jokinen R, Rinnankoski-Tuikka R, Kaye S, Saarinen L, Heinonen S, Myohanen M, Rappou E, Jukarainen S, Rissanen A, Pessia A, Velagapudi V, Virtanen KA, Pirinen E, Pietilainen KH

Publisher: NATURE PUBLISHING GROUP

: 2018

: International Journal of Obesity

: INTERNATIONAL JOURNAL OF OBESITY

: INT J OBESITY

: 42

: 4

: 817

: 825

: 9

: 0307-0565

: 1476-5497

DOI: https://doi.org/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.