Sleeve Gastrectomy Reduces Hepatic Steatosis by Improving the Coordinated Regulation of Aquaglyceroporins in Adipose Tissue and Liver in Obese Rats.
BACKGROUND
Glycerol constitutes an important metabolite for the control of lipid accumulation and glucose homeostasis. Our aim was to investigate the potential role of aquaglyceroporins, which are glycerol channels mediating glycerol efflux in adipocytes (AQP3 and AQP7) and glycerol influx (AQP9) in hepatocytes, in the improvement of adiposity and hepatic steatosis after sleeve gastrectomy in an experimental model of diet-induced obesity (DIO).


METHODS
Male Wistar DIO rats (n = 161) were subjected to surgical (sham operation and sleeve gastrectomy) or dietary interventions [fed ad libitum a normal diet (ND) or a high-fat diet (HFD) or pair-fed to the amount of food eaten by sleeve-gastrectomized animals]. The tissue distribution and expression of AQPs in biopsies of epididymal (EWAT) and subcutaneous (SCWAT) white adipose tissue and liver were analyzed by real-time PCR, Western blot, and immunohistochemistry.


RESULTS
Four weeks after surgery, DIO rats undergoing sleeve gastrectomy showed a reduction in body weight, whole-body adiposity, and hepatic steatosis. DIO was associated with a tendency towards an increase in EWAT AQP3 and SCWAT AQP7 and a decrease in hepatic AQP9. Sleeve gastrectomy downregulated AQP7 in both fat depots and upregulated AQP3 in EWAT, without changing hepatic AQP9. Aqp7 transcript levels in EWAT and SCWAT were positively associated with adiposity and glycemia, while Aqp9 mRNA was negatively correlated with markers of hepatic steatosis and insulin resistance.


CONCLUSIONS
Our results show, for the first time, that sleeve gastrectomy, a widely applied bariatric surgery procedure, restores the coordinated regulation of fat-specific AQP7 and liver-specific AQP9, thereby improving whole-body adiposity and hepatic steatosis.
Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain.
Leire
L
Méndez-Giménez
Sara
S
Becerril
Rafael
R
Moncada
Víctor
V
Valentí
Beatriz
B
Ramírez
Andoni
A
Lancha
Javier
J
Gurbindo
Inmaculada
I
Balaguer
Javier A
JA
Cienfuegos
Victoria
V
Catalán
Secundino
S
Fernández
Javier
J
Gómez-Ambrosi
Amaia
A
Rodríguez
Gema
G
Frühbeck
D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D050154:Adiposity / Q000502:physiology; D000818:Animals; D051397:Aquaglyceroporins / Q000235:genetics* / Q000378:metabolism; D020346:Aquaporins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000378:metabolism*; D005743:Gastrectomy / Q000379:methods*; D015870:Gene Expression; D008099:Liver / Q000378:metabolism; D008297:Male; D009767:Obesity, Morbid / Q000235:genetics / Q000378:metabolism / Q000601:surgery*; D051381:Rats; D017208:Rats, Wistar
C491926:Aqp7 protein, rat; D051397:Aquaglyceroporins; D020346:Aquaporins