Abstract
Browning of white adipocytes has been proposed as a powerful strategy to overcome metabolic complications, since brown adipocytes are more catabolic, expending energy as a heat form. However, the biological pathways involved in the browning process are still unclear. Aquaglyceroporins are a sub-class of aquaporin water channels that also permeate glycerol and are involved in body energy homeostasis. In the adipose tissue, aquaporin-7 (AQP7) is the most representative isoform, being crucial for white adipocyte fully differentiation and glycerol metabolism. The altered expression of AQP7 is involved in the onset of obesity and metabolic disorders. Herein, we investigated if aquaglyceroporins are implicated in beige adipocyte differentiation, similar to white cells. Thus, we optimized a protocol of murine 3T3-L1 preadipocytes browning that displayed increased beige and decreased white adipose tissue features at both gene and protein levels and evaluated aquaporin expression patterns along the differentiation process together with cellular lipid content. Our results revealed that AQP7 and aquaporin-9 (AQP9) expression was downregulated throughout beige adipocyte differentiation compared to white differentiation, which may be related to the beige physiological role of heat production from oxidative metabolism, contrasting with the anabolic/catabolic lipid metabolism requiring glycerol gateways occurring in white adipose cells.
Highlights
Adipose tissue has a central role in the regulation of energy homeostasis through its metabolic and endocrine functions, and alterations in its physiological functions associated with a sedentary life and saturated fat-based diets have been related with the development of obesity [1,2]
No significant differences were observed for TBX1 expression when using different protocols, we found CD137 and TBX15 genes to be expressed at higher levels in beige (BA) than white adipocytes (WA) (Figure 2A), in accordance with the above results and validating the browning process
In the last decades, increasing brown adipose tissue (BAT) has emerged as a potential solution for obesity and type-2 diabetes [32,33]
Summary
Adipose tissue has a central role in the regulation of energy homeostasis through its metabolic and endocrine functions, and alterations in its physiological functions associated with a sedentary life and saturated fat-based diets have been related with the development of obesity [1,2]. White adipose tissue (WAT) is an anabolic tissue involved in energy storage in the triacylglycerol form, contrasting with brown adipose tissue (BAT) that is very catabolic and involved in body thermogenesis [3]. Since the accumulation of excess WAT has deleterious consequences for metabolic health and the activation of BAT confers beneficial effects on adiposity, browning the white adipose tissue has been described as a potential strategy to target and control obesity. Considering that the amount of metabolically active BAT is low in human adults and in obese and diabetic patients who require immediate therapy, new strategies to increase the capacity for adaptive thermogenesis are paramount. Comparable to white adipocytes, they can trigger the storage phenotype, depending on the surrounding environment [6]
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