WAT is now established as a major endocrine organ impacting directly or indirectly the physiological functions in almost all cell-types. Representing around 10% of total body-weight in lean adults, WAT can achieve >50% in obese subjects [4
]. It is therefore not surprising that any obesity-induced changes in WAT mitochondria can substantially disrupt whole-body energy homeostasis.
The white adipocyte displays a unique structure, most frequently seen with a single, large lipid droplet associated with relatively low cytoplasmic volume and reduced mitochondrial density. Despite containing relatively low mitochondrial mass compared to overall size, the adipocyte interprets nutritional and hormonal cues in its micro-environment, then coordinates its mitochondrial response to either oxidize incoming fatty acids (FAs) and carbohydrate fuels through the tricarboxylic acid cycle (TCA) cycle and the respiratory chain, or store these fuels safely in the form of triglycerides until whole-body energy requirements signal for their release [5
Mitochondria play an essential role for many different pathways in the adipocyte. A synchronized initiation of both adipogenesis and mitochondrial biogenesis indicate that mitochondria play a pertinent role in the differentiation and maturation of adipocytes [6
]. A recent study by Tormos and colleagues confirmed that early events of enhanced mitochondrial metabolism, biogenesis and reactive oxygen species (ROS) production (specifically through complex III of the ETC) are critical to initiate and promote
adipocyte differentiation in an mTORC1-dependent manner. Consistent with this idea, antioxidant treatment blocks adipocyte differentiation, whereas ROS, through exogenous hydrogen peroxide treatment of cells, restored the differentiation process, as judged by increased adipocyte lipid accumulation and induction of adipogenic genes [7
]. An intriguing suggestion is that ROS, primarily in the form of H2
, are essential to initiate the PPARγ transcriptional machinery necessary to evoke adipocyte differentiation. Alternatively, ROS may play an important role in insulin signal transduction [8
]. While extremely high levels of ROS unquestionably cause cellular damage, ROS production in moderation may, however, serve to maintain cellular homeostasis by creating a tolerable oxidative environment that permits and sustains pre-adipocyte differentiation without
inflicting cellular damage. Future studies examining the precise function of ROS complementing the intricate process of adipocyte differentiation should prove illuminating, particularly in the context of a metabolically not well-balanced environment.
In addition, in differentiating preadipocytes, mitochondria must generate and sustain enough ATP to support highly energy-consuming lipogenic processes, while still maintaining normal cellular activity [9
]. During nutrient uptake, mitochondria must provide acetyl-CoA derived from glucose metabolism as substrates for fatty acid (FA) synthesis. The conversion of the glucose metabolite pyruvate to acetyl-CoA occurs exclusively within the mitochondrial matrix. Furthermore, glycerol-3-phosphate, a precursor substrate for FA-esterification, is produced by mitochondria and is required for the packaging of lipids in the form of triglycerides (TGs) into the lipid-droplet. In light of this, it has been proposed that “FFA recycling in the adipocyte” (a TG-to-FA cycle) is a crucial sequence of events that determine systemic FFA concentrations [10
]. Many of these processes are substrate-driven. Given that mitochondrial β-oxidation rates are interconnected with glyceroneogenic pathways and FA-esterification processes [11
], this highlights the potential to alleviate FA flux through the oxidative pathway by capturing and esterifying fatty acids into the local TG pool.