Aquaglyceroporins Are Differentially Expressed in Beige and White Adipocytes

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.

Involvement of aquaglyceroporins in energy metabolism in health and disease

“…Lower expression and lack of regulation of aquaglyceroporins in beige adipocytes versus white adipocytes differentiated from 3T3-L1 cells are in agreement with the commitment of beige adipocytes to metabolize fat to produce heat instead of performing TAG synthesis and degradation that involves glycerol passage [128].…”

“…Beige and white adipocytes differentiated from 3T3-L1 cells display Aqp7, Aqp3 and Aqp9 mRNA levels, while only AQP9 protein levels were detected [128]. Time-course analysis of aquaglyceroporins mRNA levels during the differentiation process revealed significant increase in Aqp7 and AQP9 mRNA levels during the differentiation into white adipocyte [128].…”

An Atherogenic Diet Disturbs Aquaporin 5 Expression in Liver and Adipocyte Tissues of Apolipoprotein E-Deficient Mice: New Insights into an Old Model of Experimental Atherosclerosis

“…In addition, our present results show that AQP3 and AQP9 expression is impaired in WAT from mice fed HF diet ( Figure 6 D). Knowing that AQP3 and AQP9 are the most abundant aquaglyceroporins in mice adipose membranes [ 26 ], their downregulation might represent a cellular strategy to avoid excess glycerol efflux to be used in liver.…”

“…RNA samples were reverse transcribed using M-MLV reverse transcriptase (Promega, Madison, WI, USA) with oligo dT primers (Promega, Madison, WI, USA). Real-time PCR reactions were carried out using a CFX96 Real-Time System C1000 (BioRad, Hercules, CA, USA), the TaqMan Universal PCR Master Mix (Applied Biosystems, Foster City, CA, USA) and the following specific TaqMan pre-designed gene expression primers and probes (Applied Biosystems, Foster City, CA, USA: AQP1 (#Mm00431834_m1), AQP3 (#Mm01208559_m1), AQP5 (#Mm00437578_m1), AQP7 (#Mm00431839_m10), AQP9 (#Mm00508094_m1), and Eef2 (#Mm00833287_g1) as previously described in [ 26 ]. The Ct method (2-ΔΔCt) was used for relative quantification of target genes expression after normalization with the Eef2 reference gene [ 36 , 37 ].…”

“…In consequence, the browning of WAT has been described as a potential strategy to target and control obesity that is causally related to CVD [ 25 ]. Our previous work revealed that AQP7 and AQP9 are downregulated along the browning process, which may be related to the physiological role of BAT in heat production, contrasting with the anabolic/catabolic lipid metabolism in white adipose cells [ 26 ].…”