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Article Dans Une Revue The American Journal of Clinical Nutrition Année : 2019

Persistent low body weight in humans is associated with higher mitochondrial activity in white adipose tissue

Carles Canto
  • Fonction : Auteur
Irene Vassallo
  • Fonction : Auteur
Kaori Minehira
  • Fonction : Auteur
Ornella Cominetti
  • Fonction : Auteur
John Corthésy
  • Fonction : Auteur
Loïc Dayon
  • Fonction : Auteur
Aline Charpagne
  • Fonction : Auteur
Sylviane Métairon
  • Fonction : Auteur
Frédéric Raymond
  • Fonction : Auteur
Patrick Descombes
  • Fonction : Auteur
Radu Palaghiu
  • Fonction : Auteur
Yves Boirie
  • Fonction : Auteur
  • PersonId : 1203914
Jörg Hager
Nele Gheldof
  • Fonction : Auteur

Résumé

BACKGROUND: Constitutional thinness (CT) is a state of low but stable body weight (BMI ≤18 kg/m2). CT subjects have normal-range hormonal profiles and food intake but exhibit resistance to weight gain despite living in the modern world's obesogenic environment. OBJECTIVE: The goal of this study is to identify molecular mechanisms underlying this protective phenotype against weight gain. METHODS: We conducted a clinical overfeeding study on 30 CT subjects and 30 controls (BMI 20-25 kg/m2) matched for age and sex. We performed clinical and integrative molecular and transcriptomic analyses on white adipose and muscle tissues. RESULTS: Our results demonstrate that adipocytes were markedly smaller in CT individuals (mean ± SEM: 2174 ± 142 μm 2) compared with controls (3586 ± 216 μm2) (P < 0.01). The mitochondrial respiratory capacity was higher in CT adipose tissue, particularly at the level of complex II of the electron transport chain (2.2-fold increase; P < 0.01). This higher activity was paralleled by an increase in mitochondrial number (CT compared with control: 784 ± 27 compared with 675 ± 30 mitochondrial DNA molecules per cell; P < 0.05). No evidence for uncoupled respiration or "browning" of the white adipose tissue was found. In accordance with the mitochondrial differences, CT subjects had a distinct adipose transcriptomic profile [62 differentially expressed genes (false discovery rate of 0.1 and log fold change >0.75)], with many differentially expressed genes associating with positive metabolic outcomes. Pathway analyses revealed an increase in fatty acid oxidation ( P = 3 × 10-04) but also triglyceride biosynthesis (P = 3.6 × 10-04). No differential response to the overfeeding was observed in the 2 groups. CONCLUSIONS: The distinct molecular signature of the adipose tissue in CT individuals suggests the presence of augm ented futile lipid cycling, rather than mitochondrial uncoupling, as a way to increase energy expenditure in CT individuals. We propose that increased mitochondrial function in adipose tissue is an important mediator in sustaining the low body weight in CT individuals. This knowledge could ultimately allow more targeted approaches for weight management treatment strategies. This trial was registered at clinicaltrials.gov as NCT02004821.

Dates et versions

hal-02279015 , version 1 (04-09-2019)

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Yiin Ling, Jérôme Carayol, Bogdan Galusca, Carles Canto, Christophe Montaurier, et al.. Persistent low body weight in humans is associated with higher mitochondrial activity in white adipose tissue. The American Journal of Clinical Nutrition, 2019, 110 (3), ⟨10.1093/ajcn/nqz144⟩. ⟨hal-02279015⟩
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