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

Abstract

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.

Mitochondrial bioenergetic pathways in blood leukocyte transcriptome decrease after intensive weight loss but are rescued following weight regain in female physique athletes

“…Our findings invoke the question whether the observed transcriptomic profile for diminished mitochondrial oxidative pathways was translated into actual changes in mitochondrial bioenergetic function. A similar downregulation of mitochondrial oxidative pathways has been reported upon long‐term conventional weight loss in subcutaneous white adipose tissue 21 ; although, in skeletal muscle, the results have been more conflicting, reporting both decreased 16 and unchanged 22 mitochondrial respiratory function. Given that CR has been shown to reduce muscle mitochondrial respiration by increasing the efficiency of ETC function in animals, 23 we speculate that our observation of suppressed of mitochondrial energy production pathways leads to similar alterations in the mitochondrial bioenergetic profile and function.…”

“…Within mitochondrial biogenesis pathways (panel B), upregulated (FDR < 0.05, dark red; P value < .05, light red) genes are indicated with red color, downregulated (FDR < 0.05, dark blue, P value < .05, light blue) genes with blue color, and genes with no clear change in expression pattern with color black (A) (B) findings invoke the question whether the observed transcriptomic profile for diminished mitochondrial oxidative pathways was translated into actual changes in mitochondrial bioenergetic function. A similar downregulation of mitochondrial oxidative pathways has been reported upon long-term conventional weight loss in subcutaneous white adipose tissue 21 ; although, in skeletal muscle, the results have been more conflicting, reporting both decreased 16 and unchanged 22 F I G U R E 4 Transcriptomic activity of genes coding mitochondrial and cytosolic ribosomal proteins following the intense weight loss period.…”

CD81 Controls Beige Fat Progenitor Cell Growth and Energy Balance via FAK Signaling

“…Importantly, we found that the number of CD81 + APCs in the subcutaneous fat of human subjects showed an inverse correlation with HOMA-IR, fasting glucose levels, diastolic blood pressure, and visceral adiposity. These results are intriguing given the recent clinical observation that mitochondrial activity in the subcutaneous fat (i.e., mitochondria-enriched adipocytes) correlates inversely with fat inflammation and hyperinsulinemia, and directly with the success of dietary-based weight-loss interventions and fat-specific glucose uptake (Heinonen et al, 2017;Jokinen et al, 2018). Thus, the number of CD81 + APCs in the Article subcutaneous fat of people may serve as a useful index to predict the risk of future metabolic disorders or the future success of efforts to control body weight.…”

Oxygenation of adipose tissue: A human perspective

“…We have recently shown that diet‐induced weight loss increased WAT gene expression of mitochondrial biogenesis markers and non‐mitochondrial oxygen consumption pathways in humans, which may have contributed to the reduction in WAT pO 2 following weight loss . In contrast, instead of improving WAT mitochondrial abnormalities, weight loss downregulated mitochondrial gene expression and density, and had neither effects on mitochondrial DNA transcripts nor OXPHOS proteins . Interestingly, the latter study showed that a higher initial mitochondrial number and gene expression was related to more successful weight loss after 12‐month follow‐up.…”