Abstract
Fasting promotes longevity by reprogramming metabolic and stress resistance pathways. However, although the impact on adipose tissue physiology through hormonal inputs is well established, the direct role of fasting on adipose cells is poorly understood. Herein we show that white and beige adipocytes, as well as mouse epididymal and subcutaneous adipose depots, respond to nutrient scarcity by acquiring a brown-like phenotype. Indeed, they improve oxidative metabolism through modulating the expression of mitochondrial- and nuclear-encoded oxidative phosphorylation genes as well as mitochondrial stress defensive proteins (UCP1, SOD2). Such adaptation is placed in a canonical mitohormetic response that proceeds via mitochondrial reactive oxygen species ((mt)ROS) production and redistribution of FoxO1 transcription factor into nucleus. Nuclear FoxO1 ((n)FoxO1) mediates retrograde communication by inducing the expression of mitochondrial oxidative and stress defensive genes. Collectively, our findings describe an unusual white/beige fat cell response to nutrient availability highlighting another health-promoting mechanism of fasting.
Highlights
In the past century, the incidence of chronic age-related diseases, obesity and type 2 diabetes, has increased dramatically [1] and it has been suggested that adipose tissue might have a central role in these pathologies [2]
We demonstrate that white adipose tissue (WAT) adipocytes exploit nutrientsensitive mitochondrial reactive oxygen species (mtROS)/Nuclear FoxO1 (nFoxO1) retrograde signaling as alternative pathway to boost their mitochondrial functionality independently of adrenergic cascade
Www.impactaging.com proteins after Western blot followed by densitometric analysis. (B) OxPHOS gene expression ratio evaluated by RT‐qPCR. (C) OxPHOS protein ratio evaluated as described in (A). (D) OxPHOS gene expression ratio evaluated by calculating the ratio between mtDNA‐ (MTCO1 and ATP6) and nDNA‐encoded (SDHA and Cox4b) OxPHOS mRNAs. (E, F) Mitochondrial stress response assessed by Western blot analysis of SOD2 (E) and through RT‐qPCR of ClpP (F). (G) OxPHOS gene expression ratio evaluated as described in (D). (H) mRNA levels of
Summary
The incidence of chronic age-related diseases, obesity and type 2 diabetes, has increased dramatically [1] and it has been suggested that adipose tissue might have a central role in these pathologies [2]. Visceral white adipose tissue (WAT) progressively expands during life participating in the metabolic perturbation occurring during aging [3,4,5]. Dietary regimens that are characterized by a reduced nutrient or calorie intake lead to visceral fat lowering and delay aging [6]. Among these dietary approaches, fasting can be managed by ingesting no or minimal amounts of nutrients and calories for brief periods [7]. The gerosuppressant signaling pathways induced by fasting are well characterized in several species and tissues [6,7], evidence on WAT is weakly explored yet
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