Perturbation of glycerol metabolism in hepatocytes from n3-PUFA-depleted rats

Portois, Laurence; Zhang, Ying; Ladrière, Laurence; Perret, Jason; Louchami, Karim; Gaspard, Nathalie; Hupkens, Emeline; Bolaky, Nargis; Delforge, Valérie; Beauwens, Renaud; Malaisse, Willy; Sener, Abdullah; Carpentier, Yvon; Delporte, Christine

doi:10.3892/ijmm.2012.943

Cited by 7 publications

(7 citation statements)

References 40 publications

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“…Alternatively, mechanisms involved in intrahepatic transport of glycerol might be affected during ongoing steatosis and become defective with further evolution of damage. A reduction of hepatocyte AQP9 protein with no changes in transcript level was recently observed in n 3-PUFA (ω3 polyunsaturated fatty acids)-depleted female rats, a model of metabolic syndrome displaying several features of the disease also including liver steatosis [20]. Surprisingly, the down-regulation appeared to be accompanied by an increase in liver [U- 14 C]glycerol uptake.…”

Section: Discussionmentioning

confidence: 87%

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Liver Glycerol Permeability and Aquaporin-9 Are Dysregulated in a Murine Model of Non-Alcoholic Fatty Liver Disease

et al. 2013

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One form of liver steatosis, namely Non-Alcoholic Fatty Liver Disease (NAFLD), is a worrisome health problem worldwide characterized by intrahepatic triacylglycerol (TG) overaccumulation. NAFLD is a common feature of metabolic syndrome being often associated with obesity, dyslipidemia and diabetes and mostly closely linked to insulin resistance. The mechanism of NAFLD pathogenesis is object of intense investigation especially regarding complex systems ultimately resulting in excessive TG deposition in hepatocytes. However, scarce is the attention about the relevance of hepatic import of glycerol, the other primary source (as glycerol-3-phosphate) of increased TG in hepatocytes. Obese leptin-deficient (ob/ob) mice, an animal model of NAFLD, were used to evaluate the functional involvement of Aquaporin-9 (AQP9), the major pathway of liver glycerol entry, in hepatosteatosis. By RT-PCR and qPCR, the level of Aqp9 mRNA in the liver of starved obese mice was comparable with the corresponding control lean littermates. By immunoblotting, the AQP9 protein at the hepatocyte sinusoidal plasma membrane of obese mice was markedly lower (33%) than lean mice, a finding fully confirmed by immunohistochemistry. By stopped-flow light scattering, the liver glycerol permeability of ob/ob mice was significantly lower (53%) than lean mice, a finding consistent with both the observed down-regulation of AQP9 protein and increased level of plasma glycerol characterizing obese mice. In summary, our results suggest implication of AQP9 in liver steatosis. The reduction of hepatocyte AQP9 and, consequently, glycerol permeability might be a defensive mechanism to counteract further fat infiltration in liver parenchyma.

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Section: Discussionmentioning

confidence: 87%

“…Major functional significance was found for AQP9 in maximizing liver glycerol import during states requiring increased glucose production [14]. Relevance of AQP9 in facilitating liver uptake of glycerol for de novo synthesis of glucose during starvation had been hypothesized since several years [15], [16], [17], [18], [19], [20].…”

Section: Introductionmentioning

confidence: 99%

Liver Glycerol Permeability and Aquaporin-9 Are Dysregulated in a Murine Model of Non-Alcoholic Fatty Liver Disease

et al. 2013

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“…A reduction of hepatocyte AQP9 protein with no changes in mRNA level was observed in n3-PUFA (ω3 polyunsaturated fatty acids)-depleted female rats, a model of metabolic syndrome displaying several features of the disease also including hepatosteatosis ( 57 ). Increased liver glycerol uptake was observed despite the AQP9 downregulation, an apparent discrepancy attributed to a raise in GK activity resulting from the altered intracellular metabolism.…”

Section: Aqp9 and Altered Hepatocyte Import Of Glycerol A New Intersmentioning

confidence: 99%

Sexual Dimorphism of Adipose and Hepatic Aquaglyceroporins in Health and Metabolic Disorders

et al. 2015

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Gender differences in the relative risk of developing metabolic complications, such as insulin resistance or non-alcoholic fatty liver disease (NAFLD), have been reported. The deregulation of glycerol metabolism partly contributes to the onset of these metabolic diseases, since glycerol constitutes a key substrate for the synthesis of triacylglycerols (TAGs) as well as for hepatic gluconeogenesis. The present mini-review covers the sex-related differences in glycerol metabolism and aquaglyceroporins (AQPs) and its impact in the control of adipose and hepatic fat accumulation as well as in whole-body glucose homeostasis. Plasma glycerol concentrations are increased in women compared to men probably due to the higher lipolytic rate and larger AQP7 amounts in visceral fat as well as the well-known sexual dimorphism in fat mass with women showing higher adiposity. AQP9 represents the primary route for glycerol uptake in hepatocytes, where glycerol is converted by the glycerol-kinase enzyme into glycerol-3-phosphate, a key substrate for de novo synthesis of glucose and TAG. In spite of showing similar hepatic AQP9 protein, women exhibit lower hepatocyte glycerol permeability than men, which might contribute to their lower prevalence of insulin resistance and NAFLD.

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“…However, in patients with morbid obesity, no relationship could be found between AQP9 expression and the degree of hepatic steatosis or fibrosis ( Miranda et al, 2009 ). N3-PUFA (ω3 polyunsaturated fatty acids)-depleted female rats (an animal model of metabolic syndrome displaying various features of the disease including the hepatic over-accumulation of TAG) showed reduced AQP9 protein levels and increased hepatic glycerol uptake as compared to control animals ( Portois et al, 2012a ). It is therefore conceivable that AQP9 increases early during onset of steatosis while decreases at a later stage of the disease, when fat accumulation becomes excessive.…”

Section: Role Of Aquaglyceroporins In Livermentioning

confidence: 99%

Aquaglyceroporins: Drug Targets for Metabolic Diseases?

2018

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Aquaporins (AQPs) are a family of transmembrane channel proteins facilitating the transport of water, small solutes, and gasses across biological membranes. AQPs are expressed in all tissues and ensure multiple roles under normal and pathophysiological conditions. Aquaglyceroporins are a subfamily of AQPs permeable to glycerol in addition to water and participate thereby to energy metabolism. This review focalizes on the present knowledge of the expression, regulation and physiological roles of AQPs in adipose tissue, liver and endocrine pancreas, that are involved in energy metabolism. In addition, the review aims at summarizing the involvement of AQPs in metabolic disorders, such as obesity, diabetes and liver diseases. Finally, challenges and recent advances related to pharmacological modulation of AQPs expression and function to control and treat metabolic diseases are discussed.

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Perturbation of glycerol metabolism in hepatocytes from n3-PUFA-depleted rats

Cited by 7 publications

References 40 publications

Liver Glycerol Permeability and Aquaporin-9 Are Dysregulated in a Murine Model of Non-Alcoholic Fatty Liver Disease

Liver Glycerol Permeability and Aquaporin-9 Are Dysregulated in a Murine Model of Non-Alcoholic Fatty Liver Disease

Sexual Dimorphism of Adipose and Hepatic Aquaglyceroporins in Health and Metabolic Disorders

Aquaglyceroporins: Drug Targets for Metabolic Diseases?

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