Title:
Therapeutic targeting of metabolic organ network in non-alcoholic steatohepatitis (NASH)

 

Speaker:
Yoshihiro Ogawa M.D., Ph.D.
Department of Medical and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University; Department of Molecular and Cellular Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University; AMED-CREST

 

Abstract:
Energy homeostasis is maintained locally through cell-cell interaction and systemically through metabolic organ network. During the course of obesity, free fatty acids, when released from visceral fat depots through the macrophage-induced adipocyte lipolysis, are overflown and transported in large quantities to the liver via the portal vein, where they are accumulated as ectopic fat, thereby developing non-alcoholic fatty liver disease (NAFLD). It is likely that NAFLD occurs through the dysregulation of metabolic organ network.
Sodium glucose cotransporter 2 (SGLT2) inhibitors, an oral antidiabetic drug, promotes urinary excretion of glucose by blocking its reabsorption in the renal proximal tubules. Using genetic and acquired models of rodent obesity, we have demonstrated that SGLT2 inhibition results in increased accumulation of lipid in the adipose tissue with no marked inflammatory responses. Ectopic fat accumulated in the liver may be reduced in parallel with “healthy expansion” of the adipose tissue, thus preventing the development of hepatic steatosis. Recently, we have also found that SGLT2 inhibition prevents or at least delays the onset of NASH in a rodent model of human NASH.
Our data suggest that SGLT2 inhibitors represent a new class of drugs targeting metabolic organ network. We postulate that metabolic organ network provides the unique therapeutic opportunities for NASH.

 

References:
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