Leptin administration restores the altered adipose and hepatic expression of aquaglyceroporins improving the non-alcoholic fatty liver of ob/ob mice

Abstract

Glycerol is an important metabolite for the control of lipid accumulation in white adipose tissue (WAT) and liver. We aimed to investigate whether exogenous administration of leptin improves features of non-alcoholic fatty liver disease (NAFLD) in leptin-deficient ob/ob mice via the regulation of AQP3 and AQP7 (glycerol channels mediating glycerol efflux in adipocytes) and AQP9 (aquaglyceroporin facilitating glycerol influx in hepatocytes). Twelve-week-old male wild type and ob/ob mice were divided in three groups as follows: control, leptin-treated (1 mg/kg/d) and pair-fed. Leptin deficiency was associated with obesity and NAFLD exhibiting an AQP3 and AQP7 increase in WAT, without changes in hepatic AQP9. Adipose Aqp3 and hepatic Aqp9 transcripts positively correlated with markers of adiposity and hepatic steatosis. Chronic leptin administration (4-weeks) was associated with improved body weight, whole-body adiposity, and hepatosteatosis of ob/ob mice and to a down-regulation of AQP3, AQP7 in WAT and an up-regulation of hepatic AQP9. Acute leptin stimulation in vitro (4-h) induced the mobilization of aquaglyceroporins towards lipid droplets (AQP3) and the plasma membrane (AQP7) in murine adipocytes. Our results show that leptin restores the coordinated regulation of fat-specific AQP7 and liver-specific AQP9, a step which might prevent lipid overaccumulation in WAT and liver in obesity.

Gut microbiota-associated bile acid deconjugation accelerates hepatic steatosis in ob/ob mice

“…Similar increases in liver weight has been observed in recent studies (Rodríguez et al . ; Sutter et al . )…”

Modulation of aquaporin gene expression by n-3 long-chain PUFA lipid structures in white and brown adipose tissue from hamsters

“…The same does not apply for LEP. LEP administration has been shown to down-regulate AQP7 expression in murine subcutaneous adipocytes (46) . We found no correlation (positive or negative) between LEP and AQP7 mRNA levels in subcutaneous WAT, but instead a positive correlation in BAT that deserves further investigation.…”

AQP3 Facilitates Proliferation and Adipogenic Differentiation of Porcine Intramuscular Adipocytes

“…AQP3 has been reported to regulate PPARα by adiponectin in hepatic stellate cells (HSC) [10]. The classical secretion factor, leptin, of adipocytes can improve systemic obesity and fatty liver in mice via AQP3 in ob/ob mice [11]. AQP3 mRNA expression in human adipose tissue was reported in another study [12].…”