[Molecular Mechanism of Lifestyle-related Diseases : See Both the Wood and Trees!].

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Energy homeostasis is maintained locally through parenchymal-stromal cell interaction and systemically through metabolic organ network. In obese adipose tissue, saturated fatty acids, which are released as a danger signal from hypertrophied adipocytes, stimulates a pathogen sensor TLR4 in the infiltrating macrophages, thus establishing a vicious cycle between adipocytes and macrophages to stimulate adipose tissue inflammation. Histologically, macrophages aggregate to constitute crown-like structures (CLS), where they are thought to scavenge the residual lipid droplets of dead adipocytes. Free fatty acids, when released from obese visceral fat depots, are transported in large quantities to the liver via the portal vein, where they are accumulated as ectopic fat, thus developing non-alcoholic fatty liver disease (NAFLD). There is a unique histological feature termed÷hepatic CLS (hCLS)øin the non-alcoholic steatohepatitis (NASH) liver, where macrophages aggregate to surround dead hepatocytes with large lipid droplets. Notably, the number of hCLS is positively correlated with the extent of liver fibrosis. Our data suggest that hCLS serves as an origin of hepatic inflammation and fibrosis during the progression from simple steatosis to NASH. Sodium glucose cotransporter 2 (SGLT2) inhibitors, an oral antidiabetic drug, promotes the urinaryexcretion of glucose by blocking its reabsorp

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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